Novel antibody shifts ‘eat me/don’t eat me’ balance in refractory NHL

 

CHICAGO – A first-in-class antibody targeting the macrophage checkpoint CD47 is a promising novel immunotherapy in non-Hodgkin lymphoma, according to Ranjana H. Advani, MD, of Stanford (Calif.) Cancer Institute.

Treatment with Hu5F9-G4 (5F9), an antibody designed to overcome the “don’t eat me” signal associated with CD47, produced “encouraging” antitumor activity in a phase 1b study of 22 patients, Dr. Advani said in an oral abstract presentation at the annual meeting of the American Society of Clinical Oncology.

“5F9 was well tolerated in combination with rituximab, with no maximum tolerated dose achieved,” said Dr. Advani, noting that there were complete remissions in 43% of the refractory follicular lymphoma patients and 33% of refractory diffuse large B-cell lymphoma patients in the phase 1b/2 study.

The antibody has an on-target anemia effect that occurs upon administration, but that was mitigated considerably by a priming and maintenance dosing approach, she added.

The study has demonstrated “excellent” response rates in a highly refractory patient population, said Caron A. Jacobson, MD, of Dana-Farber Cancer Institute and Harvard Medical School in Boston. “Targeting CD47 ... really helps to shift the balance from ‘don’t eat me’ to ‘eat me,’ ” Dr. Jacobson said at the meeting.

“Importantly, we saw very little toxicity in the study, with very few grade 4 adverse events and no immune-related adverse events,” she added.

Most adverse events were grade 1 or 2, with the most common being the expected on-target anemia associated with 5F9. Using an initial priming dose of 5F9 results in a “temporary and mild decline” in hemoglobin due to clearance of aged red blood cells, Dr. Advani said.

 

The objective response rate in the study was 50%, with efficacy observed in rituximab-refractory patients, Dr. Advani said. With a median follow-up of greater than 6 months, just 1 of 11 responders had progressed. The median duration of response was not reached, with the longest complete remission lasting more than 14 months.

5F9 is able to selectively eliminate cancer cells through blockade of CD47, while rituximab enhances 5F9’s activity via antibody-dependent cellular phagocytosis, according to Dr. Advani.

“CD47 blockade takes the foot off the brakes, while rituximab puts the foot on the accelerator, leading to maximal tumor phagocytosis,” she said.

The Food and Drug Administration recently granted 5F9 a fast track designation for both diffuse large B-cell lymphoma and follicular lymphoma. Phase 2 investigations of 5F9 in these lymphomas are ongoing, Dr. Advani said.

 

The trial is sponsored by Forty Seven. Dr. Advani reported research funding from Forty Seven, which is developing 5F9, as well as disclosures related to AstraZeneca, Bayer, Bristol-Myers Squibb, Cell Medica, Genentech/Roche, Gilead Sciences, Pharmacyclics, and Seattle Genetics, among others.

SOURCE: Advani RH et al. ASCO 2018, abstract 7504.

 

CHICAGO – A first-in-class antibody targeting the macrophage checkpoint CD47 is a promising novel immunotherapy in non-Hodgkin lymphoma, according to Ranjana H. Advani, MD, of Stanford (Calif.) Cancer Institute.

Treatment with Hu5F9-G4 (5F9), an antibody designed to overcome the “don’t eat me” signal associated with CD47, produced “encouraging” antitumor activity in a phase 1b study of 22 patients, Dr. Advani said in an oral abstract presentation at the annual meeting of the American Society of Clinical Oncology.

“5F9 was well tolerated in combination with rituximab, with no maximum tolerated dose achieved,” said Dr. Advani, noting that there were complete remissions in 43% of the refractory follicular lymphoma patients and 33% of refractory diffuse large B-cell lymphoma patients in the phase 1b/2 study.

The antibody has an on-target anemia effect that occurs upon administration, but that was mitigated considerably by a priming and maintenance dosing approach, she added.

The study has demonstrated “excellent” response rates in a highly refractory patient population, said Caron A. Jacobson, MD, of Dana-Farber Cancer Institute and Harvard Medical School in Boston. “Targeting CD47 ... really helps to shift the balance from ‘don’t eat me’ to ‘eat me,’ ” Dr. Jacobson said at the meeting.

“Importantly, we saw very little toxicity in the study, with very few grade 4 adverse events and no immune-related adverse events,” she added.

Most adverse events were grade 1 or 2, with the most common being the expected on-target anemia associated with 5F9. Using an initial priming dose of 5F9 results in a “temporary and mild decline” in hemoglobin due to clearance of aged red blood cells, Dr. Advani said.

 

The objective response rate in the study was 50%, with efficacy observed in rituximab-refractory patients, Dr. Advani said. With a median follow-up of greater than 6 months, just 1 of 11 responders had progressed. The median duration of response was not reached, with the longest complete remission lasting more than 14 months.

5F9 is able to selectively eliminate cancer cells through blockade of CD47, while rituximab enhances 5F9’s activity via antibody-dependent cellular phagocytosis, according to Dr. Advani.

“CD47 blockade takes the foot off the brakes, while rituximab puts the foot on the accelerator, leading to maximal tumor phagocytosis,” she said.

The Food and Drug Administration recently granted 5F9 a fast track designation for both diffuse large B-cell lymphoma and follicular lymphoma. Phase 2 investigations of 5F9 in these lymphomas are ongoing, Dr. Advani said.

 

The trial is sponsored by Forty Seven. Dr. Advani reported research funding from Forty Seven, which is developing 5F9, as well as disclosures related to AstraZeneca, Bayer, Bristol-Myers Squibb, Cell Medica, Genentech/Roche, Gilead Sciences, Pharmacyclics, and Seattle Genetics, among others.

SOURCE: Advani RH et al. ASCO 2018, abstract 7504.

 

CHICAGO – A first-in-class antibody targeting the macrophage checkpoint CD47 is a promising novel immunotherapy in non-Hodgkin lymphoma, according to Ranjana H. Advani, MD, of Stanford (Calif.) Cancer Institute.

Treatment with Hu5F9-G4 (5F9), an antibody designed to overcome the “don’t eat me” signal associated with CD47, produced “encouraging” antitumor activity in a phase 1b study of 22 patients, Dr. Advani said in an oral abstract presentation at the annual meeting of the American Society of Clinical Oncology.

“5F9 was well tolerated in combination with rituximab, with no maximum tolerated dose achieved,” said Dr. Advani, noting that there were complete remissions in 43% of the refractory follicular lymphoma patients and 33% of refractory diffuse large B-cell lymphoma patients in the phase 1b/2 study.

The antibody has an on-target anemia effect that occurs upon administration, but that was mitigated considerably by a priming and maintenance dosing approach, she added.

The study has demonstrated “excellent” response rates in a highly refractory patient population, said Caron A. Jacobson, MD, of Dana-Farber Cancer Institute and Harvard Medical School in Boston. “Targeting CD47 ... really helps to shift the balance from ‘don’t eat me’ to ‘eat me,’ ” Dr. Jacobson said at the meeting.

“Importantly, we saw very little toxicity in the study, with very few grade 4 adverse events and no immune-related adverse events,” she added.

Most adverse events were grade 1 or 2, with the most common being the expected on-target anemia associated with 5F9. Using an initial priming dose of 5F9 results in a “temporary and mild decline” in hemoglobin due to clearance of aged red blood cells, Dr. Advani said.

 

The objective response rate in the study was 50%, with efficacy observed in rituximab-refractory patients, Dr. Advani said. With a median follow-up of greater than 6 months, just 1 of 11 responders had progressed. The median duration of response was not reached, with the longest complete remission lasting more than 14 months.

5F9 is able to selectively eliminate cancer cells through blockade of CD47, while rituximab enhances 5F9’s activity via antibody-dependent cellular phagocytosis, according to Dr. Advani.

“CD47 blockade takes the foot off the brakes, while rituximab puts the foot on the accelerator, leading to maximal tumor phagocytosis,” she said.

The Food and Drug Administration recently granted 5F9 a fast track designation for both diffuse large B-cell lymphoma and follicular lymphoma. Phase 2 investigations of 5F9 in these lymphomas are ongoing, Dr. Advani said.

 

The trial is sponsored by Forty Seven. Dr. Advani reported research funding from Forty Seven, which is developing 5F9, as well as disclosures related to AstraZeneca, Bayer, Bristol-Myers Squibb, Cell Medica, Genentech/Roche, Gilead Sciences, Pharmacyclics, and Seattle Genetics, among others.

SOURCE: Advani RH et al. ASCO 2018, abstract 7504.