Prostate Cancer
Conditions
Brief summary
PSMA ADC 2301EXT is an open-label study to further assess the anti-tumor activity as measured by radiographic imaging and biomarkers, safety and tolerability of Prostate Specific Membrane Antigen Antibody Drug Conjugate (PSMA ADC) in subjects with mCRPC. Subjects who have participated in the PSMA ADC 2301 study and who, in the opinion of the Principal Investigator are likely to benefit from continued treatment with PSMA ADC are eligible for the PSMA ADC 2301 extension study. Subjects who are benefiting from treatment may be able to receive up to an additional eight to sixteen doses (every 3 weeks) of PSMA ADC.
Interventions
DRUGPSMA ADC
Upon recommendation from the PI and after Sponsor approval, a subject benefiting from treatment could have received up to eight additional doses Q3W. Subjects were weighed prior to each cycle and dosing was calculated on a mg/kg basis prior to each dose, with a maximum weight of 100 kg for dosing calculations.
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. Subjects who have completed the PSMA ADC 2301 study and who, in the opinion of the investigator, are likely to benefit from continued treatment with PSMA ADC 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 3. If chemically castrated, subjects must agree to stay on androgen-deprivation therapy for the duration of the study 4. If applicable, men must agree to commit to the use of a medically acceptable method of birth control (e.g., spermicide in conjunction with a barrier such as a condom) or sexual abstinence for the duration of the study, including 30 days after the last dose of study drug
Exclusion criteria
1. An acute infection requiring ongoing antibiotic therapy (e.g., UTI, indwelling catheter or other potential site(s) of infection) 2. History of significant hypersensitivity reactions to PSMA ADC or any of its components, or to any prior investigational or approved monoclonal antibodies (mAbs), immunoglobulin (Ig) fusion proteins (e.g., circulating neutralizing antibodies), or ADC 3. Clinically significant cardiac disease or severe debilitating pulmonary disease 4. Any recent or ongoing medical condition that may interfere with a subject's participation or compliance with the study or evaluation of PSMA ADC
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Total Serum PSA Response | 25 Weeks | Total serum PSA (prostate-specific antigen) was measured at baseline and had at least one post-baseline assessment. PSA response was examined at two levels: at least 30% decrease or at least 50% decrease in serum PSA. Response was assessed as the maximum decrease over the extension study. Response was defined as any decrease from baseline of at least 30% or 50%. |
| CTC Response | 25 weeks | Circulating tumor cells (CTC) response was measured at baseline and had at least one post-baseline assessment. Response was assessed as the maximum decrease over the extension study. Response was defined as any decrease from baseline of at least 50%. |
| Overall Radiologic Response | 25 weeks | Overall radiologic response was measured at baseline and post-baseline. 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 |
|---|---|
| PSMA ADC Chemotherapy-experienced Subjects started the extension study at the same dose received upon completion of the core PSMA ADC 2301 study. Each Prostate Specific Membrane Antigen Antibody Drug Conjugate (PSMA ADC) dose was administered as an IV infusion over approximately 60 minutes once every three weeks (Q3W) for up to eight doses, unless a dose delay or dose reduction was required.
PSMA ADC: Upon recommendation from the PI and after Sponsor approval, a subject benefitting from treatment could have received up to eight additional doses Q3W. Subjects were weighed prior to each cycle and dosing was calculated on a mg/kg basis prior to each dose, with a maximum weight of 100 kg for dosing calculations. | 6 |
| PSMA ADC Chemotherapy-naive Subjects started the extension study at the same dose received upon completion of the core PSMA ADC 2301 study. Each Prostate Specific Membrane Antigen Antibody Drug Conjugate (PSMA ADC) dose was administered as an IV infusion over approximately 60 minutes once every three weeks (Q3W) for up to eight doses, unless a dose delay or dose reduction was required.
PSMA ADC: Upon recommendation from the PI and after Sponsor approval, a subject benefitting from treatment could have received up to eight additional doses Q3W. Subjects were weighed prior to each cycle and dosing was calculated on a mg/kg basis prior to each dose, with a maximum weight of 100 kg for dosing calculations. | 3 |
| Total | 9 |
Baseline characteristics
| Characteristic | PSMA ADC Chemotherapy-naive | Total | PSMA ADC Chemotherapy-experienced |
|---|---|---|---|
| Age, Continuous | 77.3 years | 74.6 years | 73.2 years |
| Prostate specific antigen (PSA) | 91.3 ug/mL STANDARD_DEVIATION 125.8 | 994.6 ug/mL STANDARD_DEVIATION 1874.9 | 1446.3 ug/mL STANDARD_DEVIATION 2209.9 |
| PSA | 32.1 ug/mL | 221.2 ug/mL | 442.2 ug/mL |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 3 Participants | 9 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 6 | 3 / 3 |
| serious Total, serious adverse events | 1 / 6 | 0 / 3 |
Outcome results
Primary
CTC Response
Circulating tumor cells (CTC) response was measured at baseline and had at least one post-baseline assessment. Response was assessed as the maximum decrease over the extension study. Response was defined as any decrease from baseline of at least 50%.
Time frame: 25 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 | Value (NUMBER) |
|---|---|---|
| PSMA ADC Chemotherapy-experienced | CTC Response | 100 % of responders |
| PSMA ADC Chemotherapy-naive | CTC Response | 50 % of responders |
Primary
Overall Radiologic Response
Overall radiologic response was measured at baseline and post-baseline. 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: 25 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). All subjects (n=9) enrolled in 2301EXT were evaluated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PSMA ADC Chemotherapy-experienced | Overall Radiologic Response | Partial response | 17 % of subjects |
| PSMA ADC Chemotherapy-experienced | Overall Radiologic Response | Stable disease | 83 % of subjects |
| PSMA ADC Chemotherapy-naive | Overall Radiologic Response | Partial response | 0 % of subjects |
| PSMA ADC Chemotherapy-naive | Overall Radiologic Response | Stable disease | 100 % of subjects |
Primary
Percentage of Participants With Total Serum PSA Response
Total serum PSA (prostate-specific antigen) was measured at baseline and had at least one post-baseline assessment. PSA response was examined at two levels: at least 30% decrease or at least 50% decrease in serum PSA. Response was assessed as the maximum decrease over the extension study. Response was defined as any decrease from baseline of at least 30% or 50%.
Time frame: 25 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 | 67 % of responders |
| PSMA ADC Chemotherapy-experienced | Percentage of Participants With Total Serum PSA Response | >50% Decrease in PSA | 33 % of responders |
| PSMA ADC Chemotherapy-naive | Percentage of Participants With Total Serum PSA Response | >30% Decrease in PSA | 33 % of responders |
| PSMA ADC Chemotherapy-naive | Percentage of Participants With Total Serum PSA Response | >50% Decrease in PSA | 0 % of responders |