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SAN FRANCISCO – (LuPSMA), finds a single-center phase 2 trial to be reported at the 2019 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.
“Whilst there have been major advances in the last few years with several drugs that prolong survival in these men, the disease remains fatal in a relatively short period of time, and there is an urgent need for new effective therapies,” said lead study author Michael Hofman, MBBS, professor of nuclear medicine at the Peter MacCallum Cancer Centre, Melbourne.
LuPSMA is a radiolabeled small molecule that binds with high affinity to PSMA (prostate-specific membrane antigen), enabling targeted delivery of beta radiation to lesions throughout the body. To be eligible for the trial, patients had to have PSMA-positive disease. Results among the first 30 patients treated showed good activity and acceptable toxicity (Lancet Oncol. 2018;19:825-33), leading to enrollment of an expansion cohort of 20 patients.
With a median follow-up of 23.5 months among all 50 patients, nearly two-thirds achieved a 50% or greater reduction in their PSA level, Dr. Hofman reported in a presscast held before the symposium. Median overall survival exceeded 12 months for the whole cohort and was especially good for the subset achieving that level of PSA reduction, at 18 months.
“This is a single-arm study with no control arm. So whilst my impression is that this is a life-prolonging therapy, this is not a claim that we can make yet because there is no comparator arm with an existing treatment or therapy,” he acknowledged. However, data from the literature suggest that in the absence of this novel radioligand, the patients would likely have survived only about 6-9 months.
“These results in 50 men provide further confidence to our previously published 30-patient cohort, demonstrating high response rates and low toxicity in men with mCRPC who have progressed after multiple conventional therapies,” Dr. Hofman said. The findings also “support a novel mechanism of action for this therapy compared to existing therapies.”
The favorable data have led to initiation of two randomized controlled trials: the phase 2 TheraP trial (NCT03392428) comparing LuPSMA with cabazitaxel (Jevtana), and the phase 3 VISION trial (NCT03511664), comparing LuPSMA with best standard of care. “We really need the larger trials ... to get a confident assessment on whether it improves survival and by how much,” he maintained. “But my impression, seeing these patients come into the clinic very sick and seeing them improve on the therapy, and knowing those averages [for survival without this therapy], is that these trials are likely to be positive.”
“As a clinician, I will tell you that this is a very intriguing agent, and the VISION study, which is a registration trial, is open in the U.S.,” said ASCO expert and presscast moderator Robert Dreicer, MD, MS, MACP, FASCO, deputy director and associate director of clinical research at the University of Virginia Cancer Center and professor of medicine and urology at the University of Virginia, Charlottesville.
Study details
Of the 76 patients screened for the LuPSMA trial, 16 (21%) were ineligible because of insufficient PSMA uptake on a PSMA–FDG PET scan. “The majority of patients with this disease are suitable. Probably somewhere in the range of 20% to 30%, depending on how you measure it, may not be suitable,” Dr. Hofman said.
The 50 patients ultimately enrolled had aggressive disease, as indicated by a median PSA doubling time of 2.6 months. Most had previously received abiraterone (Zytiga), enzalutamide (Xtandi), or both (90%), as well as docetaxel (84%) or cabazitaxel (48%). “Many of these men had no further treatment options, and without this study open, they probably would have received end-of-life palliative care,” he said.
The median number of LuPSMA cycles administered was four, according to data reported in the presscast leading up to the symposium. Eight patients received fewer than four cycles because they had an exceptional response, while 10 patients did not complete all planned cycles because of disease progression.
Main results showed that PSA levels fell by at least 30% in 74% of patients, at least 50% in 64% of patients, and at least 80% in 44% of patients. Only two patients did not see any reduction. “We think this is probably a feature of our careful selection of patients with the PET scanning up front to really enrich the study for patients who are likely to benefit from the treatment,” Dr. Hofman said. The reductions in PSA were accompanied by reductions in positive lesions on PSMA–FDG PET.
For the entire cohort, median overall survival was 13.3 months. But it was significantly longer for those with versus without at least a 50% PSA decline (18.0 vs. 8.7 months; P = .001).
Fourteen patients who experienced progression on LuPSMA were given additional doses after the trial ended, as part of an off-trial expanded-access program. Fully 64% of these patients achieved a PSA reduction of at least 50%, and median overall survival in all of the retreated patients was 33 months.
Dr. Hofman disclosed that he has a consulting or advisory role with Endocyte; receives research funding (institutional) from Endocyte; and receives travel, accommodations, and/or expenses from Ipsen and Sanofi. The trial received research funding from the Peter MacCallum Cancer Centre.
SOURCE: Hofman M et al. GUCS 2019, Abstract 228.
SAN FRANCISCO – (LuPSMA), finds a single-center phase 2 trial to be reported at the 2019 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.
“Whilst there have been major advances in the last few years with several drugs that prolong survival in these men, the disease remains fatal in a relatively short period of time, and there is an urgent need for new effective therapies,” said lead study author Michael Hofman, MBBS, professor of nuclear medicine at the Peter MacCallum Cancer Centre, Melbourne.
LuPSMA is a radiolabeled small molecule that binds with high affinity to PSMA (prostate-specific membrane antigen), enabling targeted delivery of beta radiation to lesions throughout the body. To be eligible for the trial, patients had to have PSMA-positive disease. Results among the first 30 patients treated showed good activity and acceptable toxicity (Lancet Oncol. 2018;19:825-33), leading to enrollment of an expansion cohort of 20 patients.
With a median follow-up of 23.5 months among all 50 patients, nearly two-thirds achieved a 50% or greater reduction in their PSA level, Dr. Hofman reported in a presscast held before the symposium. Median overall survival exceeded 12 months for the whole cohort and was especially good for the subset achieving that level of PSA reduction, at 18 months.
“This is a single-arm study with no control arm. So whilst my impression is that this is a life-prolonging therapy, this is not a claim that we can make yet because there is no comparator arm with an existing treatment or therapy,” he acknowledged. However, data from the literature suggest that in the absence of this novel radioligand, the patients would likely have survived only about 6-9 months.
“These results in 50 men provide further confidence to our previously published 30-patient cohort, demonstrating high response rates and low toxicity in men with mCRPC who have progressed after multiple conventional therapies,” Dr. Hofman said. The findings also “support a novel mechanism of action for this therapy compared to existing therapies.”
The favorable data have led to initiation of two randomized controlled trials: the phase 2 TheraP trial (NCT03392428) comparing LuPSMA with cabazitaxel (Jevtana), and the phase 3 VISION trial (NCT03511664), comparing LuPSMA with best standard of care. “We really need the larger trials ... to get a confident assessment on whether it improves survival and by how much,” he maintained. “But my impression, seeing these patients come into the clinic very sick and seeing them improve on the therapy, and knowing those averages [for survival without this therapy], is that these trials are likely to be positive.”
“As a clinician, I will tell you that this is a very intriguing agent, and the VISION study, which is a registration trial, is open in the U.S.,” said ASCO expert and presscast moderator Robert Dreicer, MD, MS, MACP, FASCO, deputy director and associate director of clinical research at the University of Virginia Cancer Center and professor of medicine and urology at the University of Virginia, Charlottesville.
Study details
Of the 76 patients screened for the LuPSMA trial, 16 (21%) were ineligible because of insufficient PSMA uptake on a PSMA–FDG PET scan. “The majority of patients with this disease are suitable. Probably somewhere in the range of 20% to 30%, depending on how you measure it, may not be suitable,” Dr. Hofman said.
The 50 patients ultimately enrolled had aggressive disease, as indicated by a median PSA doubling time of 2.6 months. Most had previously received abiraterone (Zytiga), enzalutamide (Xtandi), or both (90%), as well as docetaxel (84%) or cabazitaxel (48%). “Many of these men had no further treatment options, and without this study open, they probably would have received end-of-life palliative care,” he said.
The median number of LuPSMA cycles administered was four, according to data reported in the presscast leading up to the symposium. Eight patients received fewer than four cycles because they had an exceptional response, while 10 patients did not complete all planned cycles because of disease progression.
Main results showed that PSA levels fell by at least 30% in 74% of patients, at least 50% in 64% of patients, and at least 80% in 44% of patients. Only two patients did not see any reduction. “We think this is probably a feature of our careful selection of patients with the PET scanning up front to really enrich the study for patients who are likely to benefit from the treatment,” Dr. Hofman said. The reductions in PSA were accompanied by reductions in positive lesions on PSMA–FDG PET.
For the entire cohort, median overall survival was 13.3 months. But it was significantly longer for those with versus without at least a 50% PSA decline (18.0 vs. 8.7 months; P = .001).
Fourteen patients who experienced progression on LuPSMA were given additional doses after the trial ended, as part of an off-trial expanded-access program. Fully 64% of these patients achieved a PSA reduction of at least 50%, and median overall survival in all of the retreated patients was 33 months.
Dr. Hofman disclosed that he has a consulting or advisory role with Endocyte; receives research funding (institutional) from Endocyte; and receives travel, accommodations, and/or expenses from Ipsen and Sanofi. The trial received research funding from the Peter MacCallum Cancer Centre.
SOURCE: Hofman M et al. GUCS 2019, Abstract 228.
SAN FRANCISCO – (LuPSMA), finds a single-center phase 2 trial to be reported at the 2019 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.
“Whilst there have been major advances in the last few years with several drugs that prolong survival in these men, the disease remains fatal in a relatively short period of time, and there is an urgent need for new effective therapies,” said lead study author Michael Hofman, MBBS, professor of nuclear medicine at the Peter MacCallum Cancer Centre, Melbourne.
LuPSMA is a radiolabeled small molecule that binds with high affinity to PSMA (prostate-specific membrane antigen), enabling targeted delivery of beta radiation to lesions throughout the body. To be eligible for the trial, patients had to have PSMA-positive disease. Results among the first 30 patients treated showed good activity and acceptable toxicity (Lancet Oncol. 2018;19:825-33), leading to enrollment of an expansion cohort of 20 patients.
With a median follow-up of 23.5 months among all 50 patients, nearly two-thirds achieved a 50% or greater reduction in their PSA level, Dr. Hofman reported in a presscast held before the symposium. Median overall survival exceeded 12 months for the whole cohort and was especially good for the subset achieving that level of PSA reduction, at 18 months.
“This is a single-arm study with no control arm. So whilst my impression is that this is a life-prolonging therapy, this is not a claim that we can make yet because there is no comparator arm with an existing treatment or therapy,” he acknowledged. However, data from the literature suggest that in the absence of this novel radioligand, the patients would likely have survived only about 6-9 months.
“These results in 50 men provide further confidence to our previously published 30-patient cohort, demonstrating high response rates and low toxicity in men with mCRPC who have progressed after multiple conventional therapies,” Dr. Hofman said. The findings also “support a novel mechanism of action for this therapy compared to existing therapies.”
The favorable data have led to initiation of two randomized controlled trials: the phase 2 TheraP trial (NCT03392428) comparing LuPSMA with cabazitaxel (Jevtana), and the phase 3 VISION trial (NCT03511664), comparing LuPSMA with best standard of care. “We really need the larger trials ... to get a confident assessment on whether it improves survival and by how much,” he maintained. “But my impression, seeing these patients come into the clinic very sick and seeing them improve on the therapy, and knowing those averages [for survival without this therapy], is that these trials are likely to be positive.”
“As a clinician, I will tell you that this is a very intriguing agent, and the VISION study, which is a registration trial, is open in the U.S.,” said ASCO expert and presscast moderator Robert Dreicer, MD, MS, MACP, FASCO, deputy director and associate director of clinical research at the University of Virginia Cancer Center and professor of medicine and urology at the University of Virginia, Charlottesville.
Study details
Of the 76 patients screened for the LuPSMA trial, 16 (21%) were ineligible because of insufficient PSMA uptake on a PSMA–FDG PET scan. “The majority of patients with this disease are suitable. Probably somewhere in the range of 20% to 30%, depending on how you measure it, may not be suitable,” Dr. Hofman said.
The 50 patients ultimately enrolled had aggressive disease, as indicated by a median PSA doubling time of 2.6 months. Most had previously received abiraterone (Zytiga), enzalutamide (Xtandi), or both (90%), as well as docetaxel (84%) or cabazitaxel (48%). “Many of these men had no further treatment options, and without this study open, they probably would have received end-of-life palliative care,” he said.
The median number of LuPSMA cycles administered was four, according to data reported in the presscast leading up to the symposium. Eight patients received fewer than four cycles because they had an exceptional response, while 10 patients did not complete all planned cycles because of disease progression.
Main results showed that PSA levels fell by at least 30% in 74% of patients, at least 50% in 64% of patients, and at least 80% in 44% of patients. Only two patients did not see any reduction. “We think this is probably a feature of our careful selection of patients with the PET scanning up front to really enrich the study for patients who are likely to benefit from the treatment,” Dr. Hofman said. The reductions in PSA were accompanied by reductions in positive lesions on PSMA–FDG PET.
For the entire cohort, median overall survival was 13.3 months. But it was significantly longer for those with versus without at least a 50% PSA decline (18.0 vs. 8.7 months; P = .001).
Fourteen patients who experienced progression on LuPSMA were given additional doses after the trial ended, as part of an off-trial expanded-access program. Fully 64% of these patients achieved a PSA reduction of at least 50%, and median overall survival in all of the retreated patients was 33 months.
Dr. Hofman disclosed that he has a consulting or advisory role with Endocyte; receives research funding (institutional) from Endocyte; and receives travel, accommodations, and/or expenses from Ipsen and Sanofi. The trial received research funding from the Peter MacCallum Cancer Centre.
SOURCE: Hofman M et al. GUCS 2019, Abstract 228.
REPORTING FROM GUCS 2019
Key clinical point: Lutetium-177 PSMA-617 (LuPSMA) is highly active in PSMA-positive metastatic castrate-resistant prostate cancer.
Major finding: PSA level fell by at least 50% in 64% of men, and median overall survival was 13.3 months.
Study details: A single-center, single-arm phase 2 trial among 50 men with PSMA-positive metastatic castrate-resistant prostate cancer (LuPSMA trial).
Disclosures: Dr. Hofman disclosed that he has a consulting or advisory role with Endocyte; receives research funding (institutional) from Endocyte; and receives travel, accommodations, and/or expenses from Ipsen and Sanofi. The trial received research funding from the Peter MacCallum Cancer Centre.
Source: Hofman M et al. GUCS 2019, Abstract 228.