Prostate Cancer
Conditions
Brief summary
PSMA ADC 2301 is a Phase 2, open-label, study to assess the anti-tumor activity and tolerability of Prostate Specific Membrane Antigen Antibody Drug Conjugate (PSMA ADC) in two groups of subjects with metastatic castration-resistant prostate cancer (mCRPC). One group comprises subjects who must have received at least one taxane-containing chemotherapy regimen (e.g. docetaxel, cabazitaxel). The second group comprises subjects who are cytotoxic chemotherapy-naïve. Subjects who are cytotoxic chemotherapy-naïve must have received and progressed on-, be ineligible for, refused, have an intolerance to-, or not have access to Radium-223. Both groups of subjects must also have received and progressed on abiraterone acetate and/or enzalutamide. If a subject is unable to receive abiraterone acetate and/or enzalutamide, Sponsor approval is required for participation in the study. Subjects will receive up to eight doses of PSMA ADC approximately once every three weeks.
Interventions
DRUGPSMA ADC
PSMA ADC administered IV at 2.5 mg/kg Q3W for 8 cycles or 2.3 mg/kg Q3W for 8 cycles.
Sponsors
Progenics Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. A diagnosis of metastatic castration-resistant prostate cancer. 2. a) Prior history of treatment with at least one taxane-containing chemotherapy regimen (e.g. docetaxel, cabazitaxel). If a subject has received more than two cytotoxic chemotherapy regimens, Sponsor approval is required for study participation. OR b) No prior history of treatment with a cytotoxic chemotherapy regimen. 3. Must have received and progressed on abiraterone acetate and/or enzalutamide. If subject is unable to receive abiraterone acetate and/or enzalutamide, Sponsor approval is required for participation in the study. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. 5. Life expectancy ≥ six months. 6. Cytotoxic chemotherapy-naïve subjects ONLY must have received and progressed on-, be ineligible for, refused, have an intolerance to-, or not have access to Radium-223.
Exclusion criteria
1. Treatment within 30 days prior to first dose of study drug of the following: * External Radiation therapy * Radiopharmaceuticals * Cytotoxic chemotherapy * Treatment with an investigational agent 2. Clinically significant cardiac disease or severe debilitating pulmonary disease 3. An acute infection requiring ongoing antibiotic therapy 4. Any prior treatment with PSMA ADC or other therapies targeting PSMA, or other antibody drug conjugate (ADC) products that contain monomethyl auristatin E (MMAE) (e.g., brentuximab vedotin, glembatumumab vedotin, ASG-5ME, RG7450) unless approved by Sponsor. 5. History of drug and/or alcohol abuse 6. History of pancreatitis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Total Serum PSA Response | 24 Weeks | Total serum prostate-specific antigen (PSA) response was defined as any decrease from baseline of at least 30% or 50%. |
| CTC Response | 24 Weeks | Circulating tumor cells (CTC) response was examined at two levels: at least 30% decrease or at least 50% decrease in CTC levels. Response was defined as any decrease from baseline of at least 30% or 50%. |
| Overall Radiologic Response | 24 weeks | Overall radiologic response was measured prior to the first dose of study drug, at predose of cycle 5, and at the end of study. Imaging techniques used at screening were used throughout the study. The preferred imaging techniques include: bone scan, contrast enhanced CT of chest, contrast enhanced CT of pelvis, and contrast enhanced CT of upper & lower abdomen. Best overall radiologic response (confirmed), target and non-target lesions, was defined as responses in bone, visceral or nodal metastases according to the Modified Response Evaluation Criteria (RECIST 1.1). The best overall radiologic response is the best response recorded from the start of the treatment until disease progression/recurrence (taking, as reference for progressive disease, the smallest measurements recorded since the treatment started). The subject's best response assignment depended on the achievement of both measurement and confirmation criteria. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: PSMA ADC Chemotherapy-experienced PSMA ADC administered IV at 2.5 mg/kg Q3W for 8 cycles or 2.3 mg/kg Q3W for 8 cycles. | 84 |
| Arm 2: PSMA ADC Chemotherapy-naive PSMA ADC administered IV at 2.3 mg/kg Q3W for 8 cycles. | 35 |
| Total | 119 |
Baseline characteristics
| Characteristic | Arm 2: PSMA ADC Chemotherapy-naive | Total | Arm 1: PSMA ADC Chemotherapy-experienced |
|---|---|---|---|
| Age, Continuous | 73.1 years | 71.4 years | 70.7 years |
| Prostate specific antigen (PSA) | 220.9 ug/mL STANDARD_DEVIATION 438.35 | 633.1 ug/mL STANDARD_DEVIATION 1857.2 | 804.8 ug/mL STANDARD_DEVIATION 2173.38 |
| PSA | 94.1 ug/mL | 162.9 ug/mL | 188.9 ug/mL |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 35 Participants | 119 Participants | 84 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 84 / 84 | 35 / 35 |
| serious Total, serious adverse events | 43 / 84 | 18 / 35 |
Outcome results
Primary
CTC Response
Circulating tumor cells (CTC) response was examined at two levels: at least 30% decrease or at least 50% decrease in CTC levels. Response was defined as any decrease from baseline of at least 30% or 50%.
Time frame: 24 Weeks
Population: Both groups must also have received and progressed on abiraterone acetate and/or enzalutamide prior to the study (once these agents were commercially available for use). The population examined was those subjects with a CTC baseline value and at least one post-baseline value.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PSMA ADC Chemotherapy-experienced | CTC Response | >30% Decrease in CTC | 81 % of responders |
| PSMA ADC Chemotherapy-experienced | CTC Response | >50% Decrease in CTC | 74 % of responders |
| Chemotherapy-naive | CTC Response | >30% Decrease in CTC | 92 % of responders |
| Chemotherapy-naive | CTC Response | >50% Decrease in CTC | 85 % of responders |
Primary
Overall Radiologic Response
Overall radiologic response was measured prior to the first dose of study drug, at predose of cycle 5, and at the end of study. Imaging techniques used at screening were used throughout the study. The preferred imaging techniques include: bone scan, contrast enhanced CT of chest, contrast enhanced CT of pelvis, and contrast enhanced CT of upper & lower abdomen. Best overall radiologic response (confirmed), target and non-target lesions, was defined as responses in bone, visceral or nodal metastases according to the Modified Response Evaluation Criteria (RECIST 1.1). The best overall radiologic response is the best response recorded from the start of the treatment until disease progression/recurrence (taking, as reference for progressive disease, the smallest measurements recorded since the treatment started). The subject's best response assignment depended on the achievement of both measurement and confirmation criteria.
Time frame: 24 weeks
Population: Both groups must also have received and progressed on abiraterone acetate and/or enzalutamide prior to the study (once these agents were commercially available for use). The full modified Intention-to-Treat (mITT) population (n = 119) was examined.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PSMA ADC Chemotherapy-experienced | Overall Radiologic Response | Non-evaluable | 26 % of subjects |
| PSMA ADC Chemotherapy-experienced | Overall Radiologic Response | Partial response | 0 % of subjects |
| PSMA ADC Chemotherapy-experienced | Overall Radiologic Response | Progressive disease | 13 % of subjects |
| PSMA ADC Chemotherapy-experienced | Overall Radiologic Response | Stable disease | 61 % of subjects |
| Chemotherapy-naive | Overall Radiologic Response | Stable disease | 69 % of subjects |
| Chemotherapy-naive | Overall Radiologic Response | Non-evaluable | 17 % of subjects |
| Chemotherapy-naive | Overall Radiologic Response | Progressive disease | 9 % of subjects |
| Chemotherapy-naive | Overall Radiologic Response | Partial response | 6 % of subjects |
Primary
Percentage of Participants With Total Serum PSA Response
Total serum prostate-specific antigen (PSA) response was defined as any decrease from baseline of at least 30% or 50%.
Time frame: 24 Weeks
Population: Both groups must also have received and progressed on abiraterone acetate and/or enzalutamide prior to the study (once these agents were commercially available for use). The population examined was those subjects with a PSA baseline value and at least one post-baseline value.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PSMA ADC Chemotherapy-experienced | Percentage of Participants With Total Serum PSA Response | >30% Decrease in PSA | 29 % of responders |
| PSMA ADC Chemotherapy-experienced | Percentage of Participants With Total Serum PSA Response | >50% Decrease in PSA | 11 % of responders |
| Chemotherapy-naive | Percentage of Participants With Total Serum PSA Response | >30% Decrease in PSA | 32 % of responders |
| Chemotherapy-naive | Percentage of Participants With Total Serum PSA Response | >50% Decrease in PSA | 21 % of responders |