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Pepinemab plus avelumab provides disease control in NSCLC
ORLANDO – Combination pepinemab and avelumab is well tolerated and shows antitumor activity in patients with advanced non–small cell lung cancer (NSCLC) who progressed on prior treatment, according to interim results from a phase 1b/2 trial.
Treatment with pepinemab, an anti–semaphorin 4D antibody, and avelumab, a programmed death-ligand 1 (PD-L1) inhibitor, produced disease control rates of 59% in immunotherapy-resistant patients and 81% in immunotherapy-naive patients.
Michael Rahman Shafique, MD, of Moffitt Cancer Center in Tampa, Fla., reported these results at the ASCO-SITC Clinical Immuno-Oncology Symposium.
The CLASSICAL-Lung trial initially enrolled 12 immunotherapy-naive patients with stage IIIb/IV NSCLC into a dose-escalation phase that examined pepinemab at doses of 5, 10, and 20 mg/kg along with 10 mg/kg of avelumab every 2 weeks.
Then, the trial enrolled 50 stage IIIb/IV patients – including 18 immunotherapy-naive patients and 32 who failed prior immunotherapy – into a phase 2 dose-expansion phase.
The 10 mg/kg pepinemab dose and 10 mg/kg avelumab dose were selected for the expansion phase based on the dose-escalation results, Dr. Shafique said. He explained that all three doses were safe, but “we were saturating the target at the 10-mg dose.”
Efficacy and safety
“In general, the safety data were encouraging,” Dr. Shafique said. “This was a very well-tolerated combination with no concerning safety signals. The most common adverse events were grade 1 and grade 2 fatigue, chills, pyrexia, and no grade 5 events attributable to the combination were reported.”
In the efficacy analysis, there were 29 evaluable patients who received pepinemab and avelumab after progressing on prior immunotherapy and were followed for at least 6 months. Two of these patients experienced a confirmed partial response (PR), and 15 had stable disease, for a disease control rate of 59%. Five patients had durable clinical benefit lasting at least 23 weeks, and three remained on active treatment at last follow-up, including one who had been on treatment for more than a year.
Of 21 evaluable immunotherapy-naive patients followed for at least 6 months, 5 experienced a confirmed PR, and 12 had stable disease, for a disease control rate of 81%. Three patients had clinical benefit lasting at least a year, and two remained on study and continued to receive treatment at last follow-up.
Pre- and on-treatment biopsies performed on the same lesion about 5 weeks apart demonstrated “a pretty drastic reduction in viable tumor,” Dr. Shafique noted.
“Even in patients with stable disease, many of them had absent tumor on these repeat, on-treatment biopsies,” he said, also noting that CD8-positive T-cell density increased in most tumors following treatment in patients who had a PR or stable disease, and the levels appeared to correspond with response.
Mechanism of action
Despite advances in immunotherapy, NSCLC patients often are refractory or acquire resistance to currently available agents, but semaphorin 4D “seems to shift the balance in the microenvironment to one of myeloid-induced immune suppression and generally a protumor, if you will, microenvironment,” Dr. Shafique said.
“Blockade of semaphorin 4D with pepinemab, we think, helps relieve this suppressive environment and actually seems to stimulate infiltration of T cells and improve T-cell activity in these tumors,” he added. He went on to explain that the mechanism of action is believed to generally be through suppression of myeloid cell trafficking to the tumor and myeloid cell cytokine secretion.
Further, and more importantly for cancer immunotherapy, preclinical models suggest that anti–semaphorin 4D antibodies are synergistic with various checkpoint inhibitors, including the PD-L1 inhibitor avelumab and others, Dr. Shafique said.
Indeed, these early CLASSICAL-Lung trial findings “do support the mechanism of action being reversing this myeloid-induced suppression in the microenvironment and improving T-cell infiltration and activity,” and they support a potential benefit of combining anti–semaphorin 4D antibodies and checkpoint inhibition in advanced NSCLC after progression on prior therapy, Dr. Shafique added.
Invited discussant Timothy A. Yap, MBBS, of the University of Texas MD Anderson Cancer Center in Houston, said that “inhibition of [semaphorin 4D] promotes functional immune infiltration into the [tumor microenvironment] and, therefore, is a rational way of inhibiting tumor progression” in NSCLC and other cancers.
The CLASSICAL-Lung trial “didn’t escalate all the way to the [maximum tolerated dose] but did demonstrate durable on-treatment increases in CD8-positive T-cell infiltration, including in 79% of patients with low or null PD-L1 expression, as proof of mechanism,” Dr. Yap said, noting the responses in both immunotherapy-naive and immunotherapy-resistant patients.
“So I guess the key question will be, ‘Is this an active combination in NSCLC?’ ” Dr. Yap said. “In my opinion, yes it is, but is it going to be enough to take it past registration?”
Next steps
As next steps for the investigators, Dr. Yap suggested looking at a more specific population of PD-L1–low or –null immunotherapy-resistant NSCLC patients, considering adding a chemotherapy agent to the pepinemab/avelumab combination, or perhaps going “straight to a randomized phase 2/3 trial [comparing the combination with] pembrolizumab.”
“The investigators should also consider other tumor types beyond non–small cell lung cancer with this particular combination,” he said.
The preclinical data with respect to the anti–semaphorin 4D antibody suggest that study in combination with other agents, such as anti–CTLA-4 agents or anti-LAG3 agents, is also warranted, Dr. Yap added, noting that triplet combinations might also be worth investigating.
The CLASSICAL-Lung trial is funded by Vaccinex and Merck. Dr. Shafique reported a consulting or advisory role with GlaxoSmithKline. Dr. Yap reported relationships with numerous pharmaceutical companies, including Merck. MD Anderson’s Institute of Applied Cancer Science, where Dr. Yap serves as medical director, has a commercial interest in DNA damage response inhibitors and other inhibitors.
SOURCE: Shafique MR et al. ASCO-SITC 2020, Abstract 75.
ORLANDO – Combination pepinemab and avelumab is well tolerated and shows antitumor activity in patients with advanced non–small cell lung cancer (NSCLC) who progressed on prior treatment, according to interim results from a phase 1b/2 trial.
Treatment with pepinemab, an anti–semaphorin 4D antibody, and avelumab, a programmed death-ligand 1 (PD-L1) inhibitor, produced disease control rates of 59% in immunotherapy-resistant patients and 81% in immunotherapy-naive patients.
Michael Rahman Shafique, MD, of Moffitt Cancer Center in Tampa, Fla., reported these results at the ASCO-SITC Clinical Immuno-Oncology Symposium.
The CLASSICAL-Lung trial initially enrolled 12 immunotherapy-naive patients with stage IIIb/IV NSCLC into a dose-escalation phase that examined pepinemab at doses of 5, 10, and 20 mg/kg along with 10 mg/kg of avelumab every 2 weeks.
Then, the trial enrolled 50 stage IIIb/IV patients – including 18 immunotherapy-naive patients and 32 who failed prior immunotherapy – into a phase 2 dose-expansion phase.
The 10 mg/kg pepinemab dose and 10 mg/kg avelumab dose were selected for the expansion phase based on the dose-escalation results, Dr. Shafique said. He explained that all three doses were safe, but “we were saturating the target at the 10-mg dose.”
Efficacy and safety
“In general, the safety data were encouraging,” Dr. Shafique said. “This was a very well-tolerated combination with no concerning safety signals. The most common adverse events were grade 1 and grade 2 fatigue, chills, pyrexia, and no grade 5 events attributable to the combination were reported.”
In the efficacy analysis, there were 29 evaluable patients who received pepinemab and avelumab after progressing on prior immunotherapy and were followed for at least 6 months. Two of these patients experienced a confirmed partial response (PR), and 15 had stable disease, for a disease control rate of 59%. Five patients had durable clinical benefit lasting at least 23 weeks, and three remained on active treatment at last follow-up, including one who had been on treatment for more than a year.
Of 21 evaluable immunotherapy-naive patients followed for at least 6 months, 5 experienced a confirmed PR, and 12 had stable disease, for a disease control rate of 81%. Three patients had clinical benefit lasting at least a year, and two remained on study and continued to receive treatment at last follow-up.
Pre- and on-treatment biopsies performed on the same lesion about 5 weeks apart demonstrated “a pretty drastic reduction in viable tumor,” Dr. Shafique noted.
“Even in patients with stable disease, many of them had absent tumor on these repeat, on-treatment biopsies,” he said, also noting that CD8-positive T-cell density increased in most tumors following treatment in patients who had a PR or stable disease, and the levels appeared to correspond with response.
Mechanism of action
Despite advances in immunotherapy, NSCLC patients often are refractory or acquire resistance to currently available agents, but semaphorin 4D “seems to shift the balance in the microenvironment to one of myeloid-induced immune suppression and generally a protumor, if you will, microenvironment,” Dr. Shafique said.
“Blockade of semaphorin 4D with pepinemab, we think, helps relieve this suppressive environment and actually seems to stimulate infiltration of T cells and improve T-cell activity in these tumors,” he added. He went on to explain that the mechanism of action is believed to generally be through suppression of myeloid cell trafficking to the tumor and myeloid cell cytokine secretion.
Further, and more importantly for cancer immunotherapy, preclinical models suggest that anti–semaphorin 4D antibodies are synergistic with various checkpoint inhibitors, including the PD-L1 inhibitor avelumab and others, Dr. Shafique said.
Indeed, these early CLASSICAL-Lung trial findings “do support the mechanism of action being reversing this myeloid-induced suppression in the microenvironment and improving T-cell infiltration and activity,” and they support a potential benefit of combining anti–semaphorin 4D antibodies and checkpoint inhibition in advanced NSCLC after progression on prior therapy, Dr. Shafique added.
Invited discussant Timothy A. Yap, MBBS, of the University of Texas MD Anderson Cancer Center in Houston, said that “inhibition of [semaphorin 4D] promotes functional immune infiltration into the [tumor microenvironment] and, therefore, is a rational way of inhibiting tumor progression” in NSCLC and other cancers.
The CLASSICAL-Lung trial “didn’t escalate all the way to the [maximum tolerated dose] but did demonstrate durable on-treatment increases in CD8-positive T-cell infiltration, including in 79% of patients with low or null PD-L1 expression, as proof of mechanism,” Dr. Yap said, noting the responses in both immunotherapy-naive and immunotherapy-resistant patients.
“So I guess the key question will be, ‘Is this an active combination in NSCLC?’ ” Dr. Yap said. “In my opinion, yes it is, but is it going to be enough to take it past registration?”
Next steps
As next steps for the investigators, Dr. Yap suggested looking at a more specific population of PD-L1–low or –null immunotherapy-resistant NSCLC patients, considering adding a chemotherapy agent to the pepinemab/avelumab combination, or perhaps going “straight to a randomized phase 2/3 trial [comparing the combination with] pembrolizumab.”
“The investigators should also consider other tumor types beyond non–small cell lung cancer with this particular combination,” he said.
The preclinical data with respect to the anti–semaphorin 4D antibody suggest that study in combination with other agents, such as anti–CTLA-4 agents or anti-LAG3 agents, is also warranted, Dr. Yap added, noting that triplet combinations might also be worth investigating.
The CLASSICAL-Lung trial is funded by Vaccinex and Merck. Dr. Shafique reported a consulting or advisory role with GlaxoSmithKline. Dr. Yap reported relationships with numerous pharmaceutical companies, including Merck. MD Anderson’s Institute of Applied Cancer Science, where Dr. Yap serves as medical director, has a commercial interest in DNA damage response inhibitors and other inhibitors.
SOURCE: Shafique MR et al. ASCO-SITC 2020, Abstract 75.
ORLANDO – Combination pepinemab and avelumab is well tolerated and shows antitumor activity in patients with advanced non–small cell lung cancer (NSCLC) who progressed on prior treatment, according to interim results from a phase 1b/2 trial.
Treatment with pepinemab, an anti–semaphorin 4D antibody, and avelumab, a programmed death-ligand 1 (PD-L1) inhibitor, produced disease control rates of 59% in immunotherapy-resistant patients and 81% in immunotherapy-naive patients.
Michael Rahman Shafique, MD, of Moffitt Cancer Center in Tampa, Fla., reported these results at the ASCO-SITC Clinical Immuno-Oncology Symposium.
The CLASSICAL-Lung trial initially enrolled 12 immunotherapy-naive patients with stage IIIb/IV NSCLC into a dose-escalation phase that examined pepinemab at doses of 5, 10, and 20 mg/kg along with 10 mg/kg of avelumab every 2 weeks.
Then, the trial enrolled 50 stage IIIb/IV patients – including 18 immunotherapy-naive patients and 32 who failed prior immunotherapy – into a phase 2 dose-expansion phase.
The 10 mg/kg pepinemab dose and 10 mg/kg avelumab dose were selected for the expansion phase based on the dose-escalation results, Dr. Shafique said. He explained that all three doses were safe, but “we were saturating the target at the 10-mg dose.”
Efficacy and safety
“In general, the safety data were encouraging,” Dr. Shafique said. “This was a very well-tolerated combination with no concerning safety signals. The most common adverse events were grade 1 and grade 2 fatigue, chills, pyrexia, and no grade 5 events attributable to the combination were reported.”
In the efficacy analysis, there were 29 evaluable patients who received pepinemab and avelumab after progressing on prior immunotherapy and were followed for at least 6 months. Two of these patients experienced a confirmed partial response (PR), and 15 had stable disease, for a disease control rate of 59%. Five patients had durable clinical benefit lasting at least 23 weeks, and three remained on active treatment at last follow-up, including one who had been on treatment for more than a year.
Of 21 evaluable immunotherapy-naive patients followed for at least 6 months, 5 experienced a confirmed PR, and 12 had stable disease, for a disease control rate of 81%. Three patients had clinical benefit lasting at least a year, and two remained on study and continued to receive treatment at last follow-up.
Pre- and on-treatment biopsies performed on the same lesion about 5 weeks apart demonstrated “a pretty drastic reduction in viable tumor,” Dr. Shafique noted.
“Even in patients with stable disease, many of them had absent tumor on these repeat, on-treatment biopsies,” he said, also noting that CD8-positive T-cell density increased in most tumors following treatment in patients who had a PR or stable disease, and the levels appeared to correspond with response.
Mechanism of action
Despite advances in immunotherapy, NSCLC patients often are refractory or acquire resistance to currently available agents, but semaphorin 4D “seems to shift the balance in the microenvironment to one of myeloid-induced immune suppression and generally a protumor, if you will, microenvironment,” Dr. Shafique said.
“Blockade of semaphorin 4D with pepinemab, we think, helps relieve this suppressive environment and actually seems to stimulate infiltration of T cells and improve T-cell activity in these tumors,” he added. He went on to explain that the mechanism of action is believed to generally be through suppression of myeloid cell trafficking to the tumor and myeloid cell cytokine secretion.
Further, and more importantly for cancer immunotherapy, preclinical models suggest that anti–semaphorin 4D antibodies are synergistic with various checkpoint inhibitors, including the PD-L1 inhibitor avelumab and others, Dr. Shafique said.
Indeed, these early CLASSICAL-Lung trial findings “do support the mechanism of action being reversing this myeloid-induced suppression in the microenvironment and improving T-cell infiltration and activity,” and they support a potential benefit of combining anti–semaphorin 4D antibodies and checkpoint inhibition in advanced NSCLC after progression on prior therapy, Dr. Shafique added.
Invited discussant Timothy A. Yap, MBBS, of the University of Texas MD Anderson Cancer Center in Houston, said that “inhibition of [semaphorin 4D] promotes functional immune infiltration into the [tumor microenvironment] and, therefore, is a rational way of inhibiting tumor progression” in NSCLC and other cancers.
The CLASSICAL-Lung trial “didn’t escalate all the way to the [maximum tolerated dose] but did demonstrate durable on-treatment increases in CD8-positive T-cell infiltration, including in 79% of patients with low or null PD-L1 expression, as proof of mechanism,” Dr. Yap said, noting the responses in both immunotherapy-naive and immunotherapy-resistant patients.
“So I guess the key question will be, ‘Is this an active combination in NSCLC?’ ” Dr. Yap said. “In my opinion, yes it is, but is it going to be enough to take it past registration?”
Next steps
As next steps for the investigators, Dr. Yap suggested looking at a more specific population of PD-L1–low or –null immunotherapy-resistant NSCLC patients, considering adding a chemotherapy agent to the pepinemab/avelumab combination, or perhaps going “straight to a randomized phase 2/3 trial [comparing the combination with] pembrolizumab.”
“The investigators should also consider other tumor types beyond non–small cell lung cancer with this particular combination,” he said.
The preclinical data with respect to the anti–semaphorin 4D antibody suggest that study in combination with other agents, such as anti–CTLA-4 agents or anti-LAG3 agents, is also warranted, Dr. Yap added, noting that triplet combinations might also be worth investigating.
The CLASSICAL-Lung trial is funded by Vaccinex and Merck. Dr. Shafique reported a consulting or advisory role with GlaxoSmithKline. Dr. Yap reported relationships with numerous pharmaceutical companies, including Merck. MD Anderson’s Institute of Applied Cancer Science, where Dr. Yap serves as medical director, has a commercial interest in DNA damage response inhibitors and other inhibitors.
SOURCE: Shafique MR et al. ASCO-SITC 2020, Abstract 75.
REPORTING FROM THE CLINICAL IMMUNO-ONCOLOGY SYMPOSIUM
Lymphopenia linked to worse response in RCC, bladder cancer patients on checkpoint inhibitors
ORLANDO – treated in a real-world setting.
In a retrospective study of 20 patients, those with lower pALCs and higher pNLRs were less likely to respond to checkpoint inhibitors.
Tonjeh Bah, MD, of Feist-Weiller Cancer Center at LSU Health Shreveport in Louisiana, and colleagues reported these results in a poster at the ASCO-SITC Clinical Immuno-Oncology Symposium.
Response rates were 75% in patients with pALC greater than 1,000 and 25% in patients with pALC less than 1,000. This difference was statistically significant (P = .027), Dr. Bah noted, adding that the groups were comparable with respect to age, sex, race, and type of checkpoint inhibitors used.
Similarly, response rates were 80% in patients with pNLR less than 3 (the established upper limit of normal) and 30% in patients with pNLR greater than 3 (P = .024).
Checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated protein 4 and programmed death-1 and its ligand are essential components of therapy across multiple cancer types, Dr. Bah noted in an interview. She explained that prior studies – mostly in patients with lung cancer and head and neck cancers – have also shown pALC and pNLR to be independently associated with poor checkpoint inhibitor response and worse progression-free survival.
“But this is the first study to look at the connection in kidney and bladder cancer in a real-world setting,” she said.
Dr. Bah and colleagues conducted the study to test the hypothesis that “lymphopenia is a marker of immune exhaustion, which is characterized by dysfunctional T cells that have a limited antitumor effect even in the presence of [checkpoint inhibitors] and by the eventual depletion of antitumor lymphocytes,” they wrote in the poster.
Patients included in the study were all those with renal cell carcinoma (n = 13) or bladder-urothelial cancers (n = 7) who received checkpoint inhibitors at one of two medical centers in Louisiana during 2015-2019 and who had outcomes reported. Patients who attained stable disease or had partial or complete responses were categorized as responders. Patients who progressed on checkpoint inhibitors were considered nonresponders.
“Our findings were not a surprise, but they do document, for the first time and in a real-world setting, that pALC and pNLR may have prognostic utility in patients with kidney and bladder cancers who are treated with [checkpoint inhibitors],” Dr. Bah said.
She added that the findings could help determine which patients are candidates for checkpoint inhibitors, but the results require confirmation in a large, prospective study. Dr. Bah reported having no disclosures, and there was no sponsor for this study.
SOURCE: Bah T et al. ASCO-SITC 2020. Abstract 31.
ORLANDO – treated in a real-world setting.
In a retrospective study of 20 patients, those with lower pALCs and higher pNLRs were less likely to respond to checkpoint inhibitors.
Tonjeh Bah, MD, of Feist-Weiller Cancer Center at LSU Health Shreveport in Louisiana, and colleagues reported these results in a poster at the ASCO-SITC Clinical Immuno-Oncology Symposium.
Response rates were 75% in patients with pALC greater than 1,000 and 25% in patients with pALC less than 1,000. This difference was statistically significant (P = .027), Dr. Bah noted, adding that the groups were comparable with respect to age, sex, race, and type of checkpoint inhibitors used.
Similarly, response rates were 80% in patients with pNLR less than 3 (the established upper limit of normal) and 30% in patients with pNLR greater than 3 (P = .024).
Checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated protein 4 and programmed death-1 and its ligand are essential components of therapy across multiple cancer types, Dr. Bah noted in an interview. She explained that prior studies – mostly in patients with lung cancer and head and neck cancers – have also shown pALC and pNLR to be independently associated with poor checkpoint inhibitor response and worse progression-free survival.
“But this is the first study to look at the connection in kidney and bladder cancer in a real-world setting,” she said.
Dr. Bah and colleagues conducted the study to test the hypothesis that “lymphopenia is a marker of immune exhaustion, which is characterized by dysfunctional T cells that have a limited antitumor effect even in the presence of [checkpoint inhibitors] and by the eventual depletion of antitumor lymphocytes,” they wrote in the poster.
Patients included in the study were all those with renal cell carcinoma (n = 13) or bladder-urothelial cancers (n = 7) who received checkpoint inhibitors at one of two medical centers in Louisiana during 2015-2019 and who had outcomes reported. Patients who attained stable disease or had partial or complete responses were categorized as responders. Patients who progressed on checkpoint inhibitors were considered nonresponders.
“Our findings were not a surprise, but they do document, for the first time and in a real-world setting, that pALC and pNLR may have prognostic utility in patients with kidney and bladder cancers who are treated with [checkpoint inhibitors],” Dr. Bah said.
She added that the findings could help determine which patients are candidates for checkpoint inhibitors, but the results require confirmation in a large, prospective study. Dr. Bah reported having no disclosures, and there was no sponsor for this study.
SOURCE: Bah T et al. ASCO-SITC 2020. Abstract 31.
ORLANDO – treated in a real-world setting.
In a retrospective study of 20 patients, those with lower pALCs and higher pNLRs were less likely to respond to checkpoint inhibitors.
Tonjeh Bah, MD, of Feist-Weiller Cancer Center at LSU Health Shreveport in Louisiana, and colleagues reported these results in a poster at the ASCO-SITC Clinical Immuno-Oncology Symposium.
Response rates were 75% in patients with pALC greater than 1,000 and 25% in patients with pALC less than 1,000. This difference was statistically significant (P = .027), Dr. Bah noted, adding that the groups were comparable with respect to age, sex, race, and type of checkpoint inhibitors used.
Similarly, response rates were 80% in patients with pNLR less than 3 (the established upper limit of normal) and 30% in patients with pNLR greater than 3 (P = .024).
Checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated protein 4 and programmed death-1 and its ligand are essential components of therapy across multiple cancer types, Dr. Bah noted in an interview. She explained that prior studies – mostly in patients with lung cancer and head and neck cancers – have also shown pALC and pNLR to be independently associated with poor checkpoint inhibitor response and worse progression-free survival.
“But this is the first study to look at the connection in kidney and bladder cancer in a real-world setting,” she said.
Dr. Bah and colleagues conducted the study to test the hypothesis that “lymphopenia is a marker of immune exhaustion, which is characterized by dysfunctional T cells that have a limited antitumor effect even in the presence of [checkpoint inhibitors] and by the eventual depletion of antitumor lymphocytes,” they wrote in the poster.
Patients included in the study were all those with renal cell carcinoma (n = 13) or bladder-urothelial cancers (n = 7) who received checkpoint inhibitors at one of two medical centers in Louisiana during 2015-2019 and who had outcomes reported. Patients who attained stable disease or had partial or complete responses were categorized as responders. Patients who progressed on checkpoint inhibitors were considered nonresponders.
“Our findings were not a surprise, but they do document, for the first time and in a real-world setting, that pALC and pNLR may have prognostic utility in patients with kidney and bladder cancers who are treated with [checkpoint inhibitors],” Dr. Bah said.
She added that the findings could help determine which patients are candidates for checkpoint inhibitors, but the results require confirmation in a large, prospective study. Dr. Bah reported having no disclosures, and there was no sponsor for this study.
SOURCE: Bah T et al. ASCO-SITC 2020. Abstract 31.
REPORTING FROM THE CLINICAL IMMUNO-ONCOLOGY SYMPOSIUM
IFN-activated monocytes show early promise for ovarian cancer
ORLANDO –
The best response observed in the open-label, dose-escalation study was a partial response in 2 of 11 evaluable patients, with about a 30% reduction in target lesion size in both patients. An additional six patients had stable disease, and three had progressive disease.
Christopher Browning Cole, MD, PhD, of the National Cancer Institute, Bethesda, Md., reported these results at the ASCO-SITC Clinical Immuno-Oncology Symposium.
The primary objective of this study was to determine safety and identify the maximum tolerated dose (MTD). The study enrolled 18 patients with metastatic or unresectable ovarian cancer that was platinum resistant or refractory. They had a median age of 61 years and had received a median of five prior therapies.
The patients were enrolled in four dose cohorts in which they were treated every 28 days with intraperitoneal peginterferon alfa-2b (Sylatron) at doses of 25-250 mcg and interferon gamma-1b (Actimmune) at doses of 5-50 mcg, with or without autologous monocytes (75-750 x 106 cells).
In all, 15 patients were assigned to dose levels that included monocytes (dose levels 2, 3, and 4). Two of these patients were unable to tolerate apheresis and were reallocated, after two to four cycles of therapy, to “dose level 3-b,” which included 250 mcg of peginterferon alfa-2b, 50 mcg of interferon gamma-1b, and no monocytes, Dr. Cole said.
Results
Based on overall safety and tolerability, the highest dose (250 mcg of peginterferon alfa-2b, 50 mcg of interferon gamma-1b, and 750 x 106 autologous monocytes) was the MTD. Six patients received this dose.
One of the partial responders received one cycle of the MTD, and the other received eight cycles of the lowest dose (25 mcg of peginterferon alfa-2b, 5 mcg of interferon gamma-1b, and no monocytes).
The median number of cycles patients received was 3.2, but “several patients stayed on treatment much longer than that,” Dr. Cole said. Two patients are still on study, one of whom has received 10 cycles to date.
Toxicities were “largely expected” based on prior studies, and included fatigue, nausea, and abdominal pain, Dr. Cole said. He added that monocyte collection by apheresis was “tolerated pretty well” by all but the two patients reallocated to dose level 3-b, and no grade 4 or 5 toxicities occurred.
There was one grade 3 peritoneal infection associated with a catheter used for monocyte administration. After a switch to port access for administration, no other such complications occurred, Dr. Cole noted.
Rationale and next steps
“There were three sets of studies that really provided the basis for [this trial],” Dr. Cole said, explaining that the first involves the “long-standing observation that ovarian cancer is really a peritoneal disease.”
“This has led to a lot of interest in directing therapies directly to the tumor in the peritoneum ... and many of these trials have shown some really impressive results in terms of [overall survival] advantage in long-term follow up,” he added.
The second set includes pioneering studies using interferons, which are capable of activating innate immune cells, intraperitoneally to treat ovarian cancer. Interferon-gamma and interferon-alfa showed particular promise.
The third set of studies, including extensive preclinical data, shows that autologous monocytes can be activated by interferon-gamma and interferon-alfa to become tumoricidal, Dr. Cole said.
The findings of the current study support further assessment of this approach, he said, adding that exploratory analyses are ongoing to measure plasma cytokines at baseline and after therapy, specifically looking for cytokines secreted by activated monocytes.
In addition to interferon-gamma, several cytokines were present at detectable levels in the blood, including interleukin-6 and tumor necrosis factor–alpha, Dr. Cole noted.
He and colleagues seek to understand changes in immune cell populations induced by the therapy. They have developed a comprehensive set of panels to look at ligands and markers reflective of immune system activation, and “markers which might be targets for future therapies, potentially allowing us to develop some rational combinations, such as [programmed death-1, programmed death-ligand 1, and cytotoxic T-lymphocyte-associated antigen 4],” he added.
“What we’d like to do next is enroll an expansion cohort at the MTD to learn more about efficacy and immunomodulatory effects of this regimen, particularly ... what’s happening with the immune system in the tumor microenvironment, so we’re going to perform tumor biopsies before and after therapy to learn a little more about that,” Dr. Cole said. “What we ultimately envision this regimen becoming is a platform to combine intraperitoneal cellular immune therapies in the innate immune system with other immunotherapies, such as systemic therapy targeting the adaptive immune system.”
The National Institutes of Health funded the study. Dr. Cole reported having no disclosures.
SOURCE: Cole C et al. ASCO-SITC: Abstract 1.
ORLANDO –
The best response observed in the open-label, dose-escalation study was a partial response in 2 of 11 evaluable patients, with about a 30% reduction in target lesion size in both patients. An additional six patients had stable disease, and three had progressive disease.
Christopher Browning Cole, MD, PhD, of the National Cancer Institute, Bethesda, Md., reported these results at the ASCO-SITC Clinical Immuno-Oncology Symposium.
The primary objective of this study was to determine safety and identify the maximum tolerated dose (MTD). The study enrolled 18 patients with metastatic or unresectable ovarian cancer that was platinum resistant or refractory. They had a median age of 61 years and had received a median of five prior therapies.
The patients were enrolled in four dose cohorts in which they were treated every 28 days with intraperitoneal peginterferon alfa-2b (Sylatron) at doses of 25-250 mcg and interferon gamma-1b (Actimmune) at doses of 5-50 mcg, with or without autologous monocytes (75-750 x 106 cells).
In all, 15 patients were assigned to dose levels that included monocytes (dose levels 2, 3, and 4). Two of these patients were unable to tolerate apheresis and were reallocated, after two to four cycles of therapy, to “dose level 3-b,” which included 250 mcg of peginterferon alfa-2b, 50 mcg of interferon gamma-1b, and no monocytes, Dr. Cole said.
Results
Based on overall safety and tolerability, the highest dose (250 mcg of peginterferon alfa-2b, 50 mcg of interferon gamma-1b, and 750 x 106 autologous monocytes) was the MTD. Six patients received this dose.
One of the partial responders received one cycle of the MTD, and the other received eight cycles of the lowest dose (25 mcg of peginterferon alfa-2b, 5 mcg of interferon gamma-1b, and no monocytes).
The median number of cycles patients received was 3.2, but “several patients stayed on treatment much longer than that,” Dr. Cole said. Two patients are still on study, one of whom has received 10 cycles to date.
Toxicities were “largely expected” based on prior studies, and included fatigue, nausea, and abdominal pain, Dr. Cole said. He added that monocyte collection by apheresis was “tolerated pretty well” by all but the two patients reallocated to dose level 3-b, and no grade 4 or 5 toxicities occurred.
There was one grade 3 peritoneal infection associated with a catheter used for monocyte administration. After a switch to port access for administration, no other such complications occurred, Dr. Cole noted.
Rationale and next steps
“There were three sets of studies that really provided the basis for [this trial],” Dr. Cole said, explaining that the first involves the “long-standing observation that ovarian cancer is really a peritoneal disease.”
“This has led to a lot of interest in directing therapies directly to the tumor in the peritoneum ... and many of these trials have shown some really impressive results in terms of [overall survival] advantage in long-term follow up,” he added.
The second set includes pioneering studies using interferons, which are capable of activating innate immune cells, intraperitoneally to treat ovarian cancer. Interferon-gamma and interferon-alfa showed particular promise.
The third set of studies, including extensive preclinical data, shows that autologous monocytes can be activated by interferon-gamma and interferon-alfa to become tumoricidal, Dr. Cole said.
The findings of the current study support further assessment of this approach, he said, adding that exploratory analyses are ongoing to measure plasma cytokines at baseline and after therapy, specifically looking for cytokines secreted by activated monocytes.
In addition to interferon-gamma, several cytokines were present at detectable levels in the blood, including interleukin-6 and tumor necrosis factor–alpha, Dr. Cole noted.
He and colleagues seek to understand changes in immune cell populations induced by the therapy. They have developed a comprehensive set of panels to look at ligands and markers reflective of immune system activation, and “markers which might be targets for future therapies, potentially allowing us to develop some rational combinations, such as [programmed death-1, programmed death-ligand 1, and cytotoxic T-lymphocyte-associated antigen 4],” he added.
“What we’d like to do next is enroll an expansion cohort at the MTD to learn more about efficacy and immunomodulatory effects of this regimen, particularly ... what’s happening with the immune system in the tumor microenvironment, so we’re going to perform tumor biopsies before and after therapy to learn a little more about that,” Dr. Cole said. “What we ultimately envision this regimen becoming is a platform to combine intraperitoneal cellular immune therapies in the innate immune system with other immunotherapies, such as systemic therapy targeting the adaptive immune system.”
The National Institutes of Health funded the study. Dr. Cole reported having no disclosures.
SOURCE: Cole C et al. ASCO-SITC: Abstract 1.
ORLANDO –
The best response observed in the open-label, dose-escalation study was a partial response in 2 of 11 evaluable patients, with about a 30% reduction in target lesion size in both patients. An additional six patients had stable disease, and three had progressive disease.
Christopher Browning Cole, MD, PhD, of the National Cancer Institute, Bethesda, Md., reported these results at the ASCO-SITC Clinical Immuno-Oncology Symposium.
The primary objective of this study was to determine safety and identify the maximum tolerated dose (MTD). The study enrolled 18 patients with metastatic or unresectable ovarian cancer that was platinum resistant or refractory. They had a median age of 61 years and had received a median of five prior therapies.
The patients were enrolled in four dose cohorts in which they were treated every 28 days with intraperitoneal peginterferon alfa-2b (Sylatron) at doses of 25-250 mcg and interferon gamma-1b (Actimmune) at doses of 5-50 mcg, with or without autologous monocytes (75-750 x 106 cells).
In all, 15 patients were assigned to dose levels that included monocytes (dose levels 2, 3, and 4). Two of these patients were unable to tolerate apheresis and were reallocated, after two to four cycles of therapy, to “dose level 3-b,” which included 250 mcg of peginterferon alfa-2b, 50 mcg of interferon gamma-1b, and no monocytes, Dr. Cole said.
Results
Based on overall safety and tolerability, the highest dose (250 mcg of peginterferon alfa-2b, 50 mcg of interferon gamma-1b, and 750 x 106 autologous monocytes) was the MTD. Six patients received this dose.
One of the partial responders received one cycle of the MTD, and the other received eight cycles of the lowest dose (25 mcg of peginterferon alfa-2b, 5 mcg of interferon gamma-1b, and no monocytes).
The median number of cycles patients received was 3.2, but “several patients stayed on treatment much longer than that,” Dr. Cole said. Two patients are still on study, one of whom has received 10 cycles to date.
Toxicities were “largely expected” based on prior studies, and included fatigue, nausea, and abdominal pain, Dr. Cole said. He added that monocyte collection by apheresis was “tolerated pretty well” by all but the two patients reallocated to dose level 3-b, and no grade 4 or 5 toxicities occurred.
There was one grade 3 peritoneal infection associated with a catheter used for monocyte administration. After a switch to port access for administration, no other such complications occurred, Dr. Cole noted.
Rationale and next steps
“There were three sets of studies that really provided the basis for [this trial],” Dr. Cole said, explaining that the first involves the “long-standing observation that ovarian cancer is really a peritoneal disease.”
“This has led to a lot of interest in directing therapies directly to the tumor in the peritoneum ... and many of these trials have shown some really impressive results in terms of [overall survival] advantage in long-term follow up,” he added.
The second set includes pioneering studies using interferons, which are capable of activating innate immune cells, intraperitoneally to treat ovarian cancer. Interferon-gamma and interferon-alfa showed particular promise.
The third set of studies, including extensive preclinical data, shows that autologous monocytes can be activated by interferon-gamma and interferon-alfa to become tumoricidal, Dr. Cole said.
The findings of the current study support further assessment of this approach, he said, adding that exploratory analyses are ongoing to measure plasma cytokines at baseline and after therapy, specifically looking for cytokines secreted by activated monocytes.
In addition to interferon-gamma, several cytokines were present at detectable levels in the blood, including interleukin-6 and tumor necrosis factor–alpha, Dr. Cole noted.
He and colleagues seek to understand changes in immune cell populations induced by the therapy. They have developed a comprehensive set of panels to look at ligands and markers reflective of immune system activation, and “markers which might be targets for future therapies, potentially allowing us to develop some rational combinations, such as [programmed death-1, programmed death-ligand 1, and cytotoxic T-lymphocyte-associated antigen 4],” he added.
“What we’d like to do next is enroll an expansion cohort at the MTD to learn more about efficacy and immunomodulatory effects of this regimen, particularly ... what’s happening with the immune system in the tumor microenvironment, so we’re going to perform tumor biopsies before and after therapy to learn a little more about that,” Dr. Cole said. “What we ultimately envision this regimen becoming is a platform to combine intraperitoneal cellular immune therapies in the innate immune system with other immunotherapies, such as systemic therapy targeting the adaptive immune system.”
The National Institutes of Health funded the study. Dr. Cole reported having no disclosures.
SOURCE: Cole C et al. ASCO-SITC: Abstract 1.
REPORTING FROM THE CLINICAL IMMUNO-ONCOLOGY SYMPOSIUM
Model reveals genes associated with prognosis in ER+, HER2– breast cancer
ORLANDO – , according to new research.
Yara Abdou, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., and colleagues presented this work in a poster at the ASCO-SITC Clinical Immuno-Oncology Symposium.
The model used 50 cycles of machine learning to cluster 98 patients from The Cancer Genome Atlas Program into high- and low-risk groups based on mRNA expression of 26 gene groups.
The gene groups consisted of 191 genes enriched in cellular and noncellular elements of the tumor microenvironment. Mutational burden and clinical outcomes data for the patients also were considered, Dr. Abdou explained in an interview.
Kaplan-Meier curves were created for each group by K-means clustering, survival differences between the two groups were assessed, and correlations among the various gene groups were analyzed.
Five identified genes were associated with poor prognosis: LOXL2, PHEX, ACTA2, MEGF9, and TNFSF4. Fifteen genes were associated with good prognosis: CD8A, CD8B, FCRL3, GZMK, CD3E, CCL5, TP53, ICAM3, CD247, IFNG, IFNGR1, ICAM4, SHH, HLA-DOB, and CXCR3.
The Kaplan-Meier curves showed a significant difference in survival between the two groups (hazard ratio, 2.878; P = .05), confirming the validity of the risk score modeling, Dr. Abdou said.
Immune profiling showed that expression of genes associated with desmoplastic reaction, neutrophils, and immunosuppressive cytokines were higher in the high-risk group, whereas expression of genes related to immune system activation were higher in the low-risk group (P less than .05).
Stroma in the tumor microenvironment is known to affect prognosis and response to therapy in patients with breast cancer, but few mathematical models exist to determine prognosis based on mRNA expressivity in the tumor microenvironment, Dr. Abdou said, explaining the rationale for the study.
The findings suggest that when genomic profile information is available for a given patient in the clinic, this machine learning–assisted risk scoring approach could have prognostic value, she said, noting that the model also will be assessed in patients with other types of breast cancer.
Dr. Abdou reported having no disclosures.
SOURCE: Abdou Y et al. ASCO-SITC. Poster A3.
ORLANDO – , according to new research.
Yara Abdou, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., and colleagues presented this work in a poster at the ASCO-SITC Clinical Immuno-Oncology Symposium.
The model used 50 cycles of machine learning to cluster 98 patients from The Cancer Genome Atlas Program into high- and low-risk groups based on mRNA expression of 26 gene groups.
The gene groups consisted of 191 genes enriched in cellular and noncellular elements of the tumor microenvironment. Mutational burden and clinical outcomes data for the patients also were considered, Dr. Abdou explained in an interview.
Kaplan-Meier curves were created for each group by K-means clustering, survival differences between the two groups were assessed, and correlations among the various gene groups were analyzed.
Five identified genes were associated with poor prognosis: LOXL2, PHEX, ACTA2, MEGF9, and TNFSF4. Fifteen genes were associated with good prognosis: CD8A, CD8B, FCRL3, GZMK, CD3E, CCL5, TP53, ICAM3, CD247, IFNG, IFNGR1, ICAM4, SHH, HLA-DOB, and CXCR3.
The Kaplan-Meier curves showed a significant difference in survival between the two groups (hazard ratio, 2.878; P = .05), confirming the validity of the risk score modeling, Dr. Abdou said.
Immune profiling showed that expression of genes associated with desmoplastic reaction, neutrophils, and immunosuppressive cytokines were higher in the high-risk group, whereas expression of genes related to immune system activation were higher in the low-risk group (P less than .05).
Stroma in the tumor microenvironment is known to affect prognosis and response to therapy in patients with breast cancer, but few mathematical models exist to determine prognosis based on mRNA expressivity in the tumor microenvironment, Dr. Abdou said, explaining the rationale for the study.
The findings suggest that when genomic profile information is available for a given patient in the clinic, this machine learning–assisted risk scoring approach could have prognostic value, she said, noting that the model also will be assessed in patients with other types of breast cancer.
Dr. Abdou reported having no disclosures.
SOURCE: Abdou Y et al. ASCO-SITC. Poster A3.
ORLANDO – , according to new research.
Yara Abdou, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., and colleagues presented this work in a poster at the ASCO-SITC Clinical Immuno-Oncology Symposium.
The model used 50 cycles of machine learning to cluster 98 patients from The Cancer Genome Atlas Program into high- and low-risk groups based on mRNA expression of 26 gene groups.
The gene groups consisted of 191 genes enriched in cellular and noncellular elements of the tumor microenvironment. Mutational burden and clinical outcomes data for the patients also were considered, Dr. Abdou explained in an interview.
Kaplan-Meier curves were created for each group by K-means clustering, survival differences between the two groups were assessed, and correlations among the various gene groups were analyzed.
Five identified genes were associated with poor prognosis: LOXL2, PHEX, ACTA2, MEGF9, and TNFSF4. Fifteen genes were associated with good prognosis: CD8A, CD8B, FCRL3, GZMK, CD3E, CCL5, TP53, ICAM3, CD247, IFNG, IFNGR1, ICAM4, SHH, HLA-DOB, and CXCR3.
The Kaplan-Meier curves showed a significant difference in survival between the two groups (hazard ratio, 2.878; P = .05), confirming the validity of the risk score modeling, Dr. Abdou said.
Immune profiling showed that expression of genes associated with desmoplastic reaction, neutrophils, and immunosuppressive cytokines were higher in the high-risk group, whereas expression of genes related to immune system activation were higher in the low-risk group (P less than .05).
Stroma in the tumor microenvironment is known to affect prognosis and response to therapy in patients with breast cancer, but few mathematical models exist to determine prognosis based on mRNA expressivity in the tumor microenvironment, Dr. Abdou said, explaining the rationale for the study.
The findings suggest that when genomic profile information is available for a given patient in the clinic, this machine learning–assisted risk scoring approach could have prognostic value, she said, noting that the model also will be assessed in patients with other types of breast cancer.
Dr. Abdou reported having no disclosures.
SOURCE: Abdou Y et al. ASCO-SITC. Poster A3.
REPORTING FROM THE CLINICAL IMMUNO-ONCOLOGY SYMPOSIUM
Adding ilixadencel improved outcomes in metastatic renal cell carcinoma
ORLANDO –
The confirmed overall response rate was 42.2% (19/45) in patients who received ilixadencel plus sunitinib and 24.0% (6/25) in patients who received sunitinib monotherapy. Magnus Lindskog, MD, PhD, of Uppsala (Sweden) University Hospital, reported these results at the ASCO-SITC Immuno-Oncology Symposium.
The complete response rate was 11.1% with ilixadencel plus sunitinib and 4% with sunitinib monotherapy. The confirmed complete response rates were 6.7% and 0%, respectively.
The median duration of response was 7.1 months with ilixadencel plus sunitinib and 2.9 months with sunitinib monotherapy. The median progression-free survival was 11.8 months and 11.0 months, respectively.
There was no difference in median overall survival – a coprimary endpoint – at 18 months, nor was there a difference in progression-free survival at that time. “We do find it interesting that there is a late separation of both [survival] curves like we see in many immunotherapy trials,” Dr. Lindskog said, noting that all five complete responders in the combination therapy arm were alive at 33 months, whereas the single patient with a complete response in the monotherapy group died after 41 months.
“So far, we have 54% versus 37% still alive in the ilixadencel versus sunitinib groups,” Dr. Lindskog said, adding that the observed activity of ilixadencel appears to be driven by responses in patients with intermediate risk.
The overall survival data in the intermediate-risk patients is not mature. The overall survival in poor-risk patients was 11.6 months in the combination group and 9.3 months in the monotherapy group.
MERECA study participants were adults with a mean age of 62-64 years who were considered surgical candidates. They were enrolled from eight centers in Europe and the United States between April 2014 and January 2017 and randomized 2:1 to the combination and monotherapy arms. In all, 45 patients received their assigned treatment in the combination arm, and 25 patients received their assigned treatment in the monotherapy arm.
Patients in the ilixadencel arm were injected twice, 2 weeks apart, at the primary tumor site using CT guidance. Patients in the monotherapy arm were observed until nephrectomy. Both groups received sunitinib after nephrectomy, which was performed within 6 weeks, and all were followed for 18 months.
Treatment was well tolerated. Ilixadencel did not add any clinically meaningful treatment-related grade 3-4 adverse events or serious adverse events, Dr. Lindskog said. He noted that the most common ilixadencel-related adverse event was uncomplicated pyrexia.
There were no signs of induced autoimmunity, and although 57% of patients in the combination therapy group developed ilixadencel-specific alloantibodies, this had no relationship to responses, Dr. Lindskog said.
“From this phase 2 study, we have confirmed the feasibility and safety of ilixadencel and sunitinib combined in newly diagnosed synchronous metastatic renal cell carcinoma patients,” he said.
He added that longer follow-up is needed to understand the late divergence in survival curves between the groups. Survival follow-up will continue for 5 years.
This study was funded by Immunicum. Dr. Lindskog disclosed relationships with Pfizer, Bristol-Myers Squibb, and Ipsen.
SOURCE: Lindskog M et al. ASCO-SITC 2020, Abstract 11.
ORLANDO –
The confirmed overall response rate was 42.2% (19/45) in patients who received ilixadencel plus sunitinib and 24.0% (6/25) in patients who received sunitinib monotherapy. Magnus Lindskog, MD, PhD, of Uppsala (Sweden) University Hospital, reported these results at the ASCO-SITC Immuno-Oncology Symposium.
The complete response rate was 11.1% with ilixadencel plus sunitinib and 4% with sunitinib monotherapy. The confirmed complete response rates were 6.7% and 0%, respectively.
The median duration of response was 7.1 months with ilixadencel plus sunitinib and 2.9 months with sunitinib monotherapy. The median progression-free survival was 11.8 months and 11.0 months, respectively.
There was no difference in median overall survival – a coprimary endpoint – at 18 months, nor was there a difference in progression-free survival at that time. “We do find it interesting that there is a late separation of both [survival] curves like we see in many immunotherapy trials,” Dr. Lindskog said, noting that all five complete responders in the combination therapy arm were alive at 33 months, whereas the single patient with a complete response in the monotherapy group died after 41 months.
“So far, we have 54% versus 37% still alive in the ilixadencel versus sunitinib groups,” Dr. Lindskog said, adding that the observed activity of ilixadencel appears to be driven by responses in patients with intermediate risk.
The overall survival data in the intermediate-risk patients is not mature. The overall survival in poor-risk patients was 11.6 months in the combination group and 9.3 months in the monotherapy group.
MERECA study participants were adults with a mean age of 62-64 years who were considered surgical candidates. They were enrolled from eight centers in Europe and the United States between April 2014 and January 2017 and randomized 2:1 to the combination and monotherapy arms. In all, 45 patients received their assigned treatment in the combination arm, and 25 patients received their assigned treatment in the monotherapy arm.
Patients in the ilixadencel arm were injected twice, 2 weeks apart, at the primary tumor site using CT guidance. Patients in the monotherapy arm were observed until nephrectomy. Both groups received sunitinib after nephrectomy, which was performed within 6 weeks, and all were followed for 18 months.
Treatment was well tolerated. Ilixadencel did not add any clinically meaningful treatment-related grade 3-4 adverse events or serious adverse events, Dr. Lindskog said. He noted that the most common ilixadencel-related adverse event was uncomplicated pyrexia.
There were no signs of induced autoimmunity, and although 57% of patients in the combination therapy group developed ilixadencel-specific alloantibodies, this had no relationship to responses, Dr. Lindskog said.
“From this phase 2 study, we have confirmed the feasibility and safety of ilixadencel and sunitinib combined in newly diagnosed synchronous metastatic renal cell carcinoma patients,” he said.
He added that longer follow-up is needed to understand the late divergence in survival curves between the groups. Survival follow-up will continue for 5 years.
This study was funded by Immunicum. Dr. Lindskog disclosed relationships with Pfizer, Bristol-Myers Squibb, and Ipsen.
SOURCE: Lindskog M et al. ASCO-SITC 2020, Abstract 11.
ORLANDO –
The confirmed overall response rate was 42.2% (19/45) in patients who received ilixadencel plus sunitinib and 24.0% (6/25) in patients who received sunitinib monotherapy. Magnus Lindskog, MD, PhD, of Uppsala (Sweden) University Hospital, reported these results at the ASCO-SITC Immuno-Oncology Symposium.
The complete response rate was 11.1% with ilixadencel plus sunitinib and 4% with sunitinib monotherapy. The confirmed complete response rates were 6.7% and 0%, respectively.
The median duration of response was 7.1 months with ilixadencel plus sunitinib and 2.9 months with sunitinib monotherapy. The median progression-free survival was 11.8 months and 11.0 months, respectively.
There was no difference in median overall survival – a coprimary endpoint – at 18 months, nor was there a difference in progression-free survival at that time. “We do find it interesting that there is a late separation of both [survival] curves like we see in many immunotherapy trials,” Dr. Lindskog said, noting that all five complete responders in the combination therapy arm were alive at 33 months, whereas the single patient with a complete response in the monotherapy group died after 41 months.
“So far, we have 54% versus 37% still alive in the ilixadencel versus sunitinib groups,” Dr. Lindskog said, adding that the observed activity of ilixadencel appears to be driven by responses in patients with intermediate risk.
The overall survival data in the intermediate-risk patients is not mature. The overall survival in poor-risk patients was 11.6 months in the combination group and 9.3 months in the monotherapy group.
MERECA study participants were adults with a mean age of 62-64 years who were considered surgical candidates. They were enrolled from eight centers in Europe and the United States between April 2014 and January 2017 and randomized 2:1 to the combination and monotherapy arms. In all, 45 patients received their assigned treatment in the combination arm, and 25 patients received their assigned treatment in the monotherapy arm.
Patients in the ilixadencel arm were injected twice, 2 weeks apart, at the primary tumor site using CT guidance. Patients in the monotherapy arm were observed until nephrectomy. Both groups received sunitinib after nephrectomy, which was performed within 6 weeks, and all were followed for 18 months.
Treatment was well tolerated. Ilixadencel did not add any clinically meaningful treatment-related grade 3-4 adverse events or serious adverse events, Dr. Lindskog said. He noted that the most common ilixadencel-related adverse event was uncomplicated pyrexia.
There were no signs of induced autoimmunity, and although 57% of patients in the combination therapy group developed ilixadencel-specific alloantibodies, this had no relationship to responses, Dr. Lindskog said.
“From this phase 2 study, we have confirmed the feasibility and safety of ilixadencel and sunitinib combined in newly diagnosed synchronous metastatic renal cell carcinoma patients,” he said.
He added that longer follow-up is needed to understand the late divergence in survival curves between the groups. Survival follow-up will continue for 5 years.
This study was funded by Immunicum. Dr. Lindskog disclosed relationships with Pfizer, Bristol-Myers Squibb, and Ipsen.
SOURCE: Lindskog M et al. ASCO-SITC 2020, Abstract 11.
REPORTING FROM THE CLINICAL IMMUNO-ONCOLOGY SYMPOSIUM