Bladder Small Cell Neuroendocrine Carcinoma, Castration-Resistant Prostate Carcinoma, Metastatic Bladder Urothelial Carcinoma, Metastatic Urethral Urothelial Carcinoma, Prostate Carcinoma Metastatic in the Bone, Prostate Neuroendocrine Neoplasm, Prostate Small Cell Carcinoma, Stage III Bladder Cancer American Joint Committee on Cancer ( AJCC) v8, Stage III Prostate Cancer AJCC v8, Stage III Urethral Cancer AJCC v8, Stage IVA Bladder Cancer AJCC v8, Stage IVB Bladder Cancer AJCC v8, Stage IV Bladder Cancer AJCC v8, Stage IV Prostate Cancer AJCC v8, Stage IV Urethral Cancer AJCC v8, Ureter Small Cell Carcinoma, Urothelial Carcinoma
Conditions
Brief summary
This phase Ib trial studies how well pembrolizumab works with combination chemotherapy in treating participants with small cell/neuroendocrine cancers of the urothelium or prostate that has spread to nearby tissue or lymph nodes or that has spread to other places in the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as etoposide, docetaxel, cisplatin, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pembrolizumab with platinum-based chemotherapy may work better in treating participants with small cell/neuroendocrine cancers of the urothelium or prostate.
Detailed description
PRIMARY OBJECTIVES: I. To evaluate the preliminary efficacy of pembrolizumab (MK-3475) in combination with standard-of-care cisplatin-based chemotherapy by assessing the durable response rate (DRR), overall response rate (ORR), duration of response (DOR), and progression free survival (PFS) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and overall survival (OS) in Cohorts 1 and 2, and radiographic PFS (rPFS) by Prostate Cancer Working Group 3 (PCWG3) and prostate-specific antigen (PSA) response in Cohort 2. SECONDARY OBJECTIVES: I. To determine the safety and tolerability of pembrolizumab in combination with etoposide and cisplatin/carboplatin or docetaxel and carboplatin assessed by parameters of adverse events (AEs). EXPLORATORY OBJECTIVES: I. Determine correlation of biomarkers including PD-L1 expression (PD-L1 positive \>= 1% by immunohistochemistry \[IHC\] using 22C3 antibody), and serum and tissue molecular (including genomic, proteomic) biomarkers that may be indicative of clinic response or safety. OUTLINE: Participants receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Courses repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Participants also receive standard of care chemotherapy comprising either etoposide IV on days 1-3 and cisplatin IV or carboplatin IV on day 1 (Cohort 1), or etoposide IV on days 1-3, carboplatin IV on day 1, and docetaxel IV on day 1 (Cohort 2). Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants are followed up at 30 days, every 9-12 weeks for up to 2 years, and then every 12 weeks thereafter.
Interventions
DRUGCarboplatin
Given IV
DRUGCisplatin
Given IV
DRUGDocetaxel
Given IV
DRUGEtoposide
Given IV
BIOLOGICALPembrolizumab
Given IV
Sponsors
Merck Sharp & Dohme LLC
Jonsson Comprehensive Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed diagnosis of locally advanced or metastatic 1) naive small cell cancer of the bladder, urethra, or upper urinary tract, or 2) primary small cell or neuroendocrine prostate cancer will be enrolled in this study. * Histological diagnosis of pure or mixed small cell or neuroendocrine cancer by a genitourinary pathologist is sufficient and confirmatory immunohistochemistry is not required. * Cohort 1 will include subjects with no prior systemic chemotherapy for locally advanced or metastatic urothelial carcinoma, with the following exception(s): * Platinum-based chemotherapy with recurrence \> 12 months from completion of therapy is permitted. * Cohort 2 will include subjects with no prior systemic chemotherapy for primary small cell prostate cancer, with the following exception(s): * Platinum-based chemotherapy with recurrence \> 12 months from completion of therapy is permitted. * Cohort 2 will include subjects with prior treatments for metastatic castration-resistant prostate cancer (mCRPC) including: * Prior chemotherapy with 2 other agents is allowed if \> 6 months elapsed from last dose (if docetaxel chemotherapy is used more than once for hormone-sensitive and for mCRPC it will be considered 1 therapy). * Ongoing androgen deprivation therapy with up to 2 second-generation hormonal manipulations (e.g. including but not limited to abiraterone acetate and/or enzalutamide). * Ongoing treatment with for bone metastasis (e.g. denosumab or zoledronic acid) is permitted. * Prior immunotherapy with sipuleucel-T is allowed if completed \> 4 weeks prior to trial enrollment. * A male participant must agree to use contraception during the treatment period and for at least 120 days after the last dose of pembrolizumab or 180 days after chemotherapy and refrain from donating sperm during this period. * A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: * Not a woman of childbearing potential (WOCBP) or * A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of pembrolizumab or 180 days after chemotherapy. * The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. * Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. * Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated within 6 months of screening. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. In addition, the availability of fresh frozen tissue is encouraged. Newly obtained biopsies are preferred to archival tissue. * Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the date of allocation. * Absolute neutrophil count (ANC) \>= 1500/uL within 10 days prior to the start of study treatment. * Platelets \>= 100 000/uL (microliter) within 10 days prior to the start of study treatment. * Hemoglobin \>= 9.0 g/dL or \>= 5.6 mmol/L within 10 days prior to the start of study treatment. * Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks. * Creatinine =\< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) \>= 30 mL/min for participant with creatinine levels \>1.5 x institutional ULN within 10 days prior to the start of study treatment. * Creatinine clearance (CrCl) should be calculated per institutional standard. * Total bilirubin =\< 1.5 ?ULN or direct bilirubin =\< ULN for participants with total bilirubin levels \> 1.5 ? ULN within 10 days prior to the start of study treatment. * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 ? ULN (=\< 5 ? ULN for participants with liver metastases) within 10 days prior to the start of study treatment. * International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 ? ULN unless participant is receiving anticoagulant therapy as long as PT or activated partial thromboplastin time (aPTT) is within therapeutic range of intended use of anticoagulants within 10 days prior to the start of study treatment.
Exclusion criteria
* Has disease suitable for local treatment with curative intent. * A WOCBP who has a positive urine pregnancy test within 72 hours prior to receiving the first dose of trial medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. * Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137). * Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to first dose of trial treatment. * Note: Participants must have recovered from all AEs due to previous therapies to =\< grade 1 or baseline. Participants with =\< grade 2 neuropathy may be eligible. * Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment. * Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=\< 2 weeks of radiotherapy) to non-central nervous system (CNS) disease. * Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette?Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist) are live attenuated vaccines and are not allowed. * Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. * Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent. * Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. * Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. * For Cohort 1, a history of prostate cancer that was identified incidentally following cystoprostatectomy for bladder cancer is acceptable provided that the PSA is \< 0.2. * Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment. * Has severe hypersensitivity (\>= grade 3) to pembrolizumab and/or any of its excipients. * Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. * Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. * Has an active infection requiring systemic therapy. * Has a known history of human immunodeficiency virus (HIV). * Has a known history of hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or known active hepatitis C virus (defined as HCV ribonucleic acid \[RNA\] \[qualitative\] is detected) infection. Note: no testing for hepatitis B and hepatitis C is required unless mandated by local health authority. * Has a known history of active TB (bacillus tuberculosis). * Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject?s participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. * Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. * Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events Per Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (Cohorts 1 and 2) | Up to 3 years | — |
| Durable Response Rate (DRR) (Cohorts 1 and 2) | At 6 months | Durable Response Rate (DRR) defined as the proportion of patients who achieved a confirmed complete or partial response (CR or PR) and maintained that response for at least 6 months. |
| Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Cohorts 1 and 2) | Up to 3 years | Overall Response Rate (ORR) defined as patients by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 exhibited a complete or partial response (CR or PR). CR defined as disappearance of all target lesions. PR defined as \>= 30% decrease in sum of the longest diameter of target lesions. . |
| Duration of Response (DOR) Per RECIST 1.1 (Cohorts 1 and 2) | From the first documented CR or PR up to 3 years | Duration of Response (DOR) defined as the time from the first documented CR or PR until radiograph disease progression or Prostate-Specific Antigen (PSA) progression. |
| Proportion of Participants With Progression Free Survival at 12 and 24 Months | 12 months and 24 months. | Progression Free Survival (PFS) defined as the time from the first day of study treatment to first documented disease progression by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 as a 20% increase in the sum of the longest diameter of target lesions, a measurable increase in a non-target lesion, or the appearance of new lesion(s). |
| Proportion of Participants With Overall Survival of Cohort 1 and 2 at 12 and 24 Months | 12 months and 24 months. | Overall Survival (OS) defined as the time from the first day of study treatment to the time of death from any cause. |
| Portion of Participants With Radiographic Progression-free Survival (rPFS) by Prostate Cancer Working Group 3 (PCWG3) at 12 and 24 Months (Cohort 2) | 12 months and 24 months. | PCWG3 is specifically designed for prostate cancer and incorporates both soft tissue and bone response assessment. RECIST 1.1 is used for evaluating responses in solid tumors, while PCWG3 combines Response evaluation criteria in solid tumors (RECIST)1.1 for soft tissue assessment with specific criteria for bone scans. The PCWG3 response criteria was used to report the portion of participants with rPFS at their 12 and 24 month assessments. |
Other
| Measure | Time frame |
|---|---|
| Percentage of Participants With Programmed Death-ligand 1 (PD-L1) Combined Positive Score (CPS) Greater Than 10, at 12 Months | at 12 months |
Countries
United States
Participant flow
Recruitment details
This trial was opened for accrual with the first enrollment on January 11, 2019. The study closed to accrual on May 5, 2022.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Metastatic or Locally Advanced Naive Small Cell Bladder Cancer Participants receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Participants also receive standard of care chemotherapy comprising etoposide IV on days 1-3 and cisplatin IV or carboplatin IV on day 1 (Cohort 1). Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Carboplatin: Given IV
Cisplatin: Given IV
Docetaxel: Given IV
Etoposide: Given IV
Pembrolizumab: Given IV | 7 |
| Cohort 2: Small Cell or Neuroendocrine Prostate Cancer Participants receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Participants also receive standard of care chemotherapy comprising etoposide IV on days 1-3, carboplatin IV on day 1, and docetaxel IV on day 1 (Cohort 2). Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. | 8 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Follow-up Period | Withdrawal by Subject | 0 | 1 |
| Treatment Period | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort 1: Metastatic or Locally Advanced Naive Small Cell Bladder Cancer | Cohort 2: Small Cell or Neuroendocrine Prostate Cancer | Total |
|---|---|---|---|
| Age, Customized >50<=60 years | 1 Participants | 3 Participants | 4 Participants |
| Age, Customized >60<=70 years | 3 Participants | 4 Participants | 7 Participants |
| Age, Customized >70<=80 years | 2 Participants | 1 Participants | 3 Participants |
| Age, Customized >80 years | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 7 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 7 Participants | 14 Participants |
| Region of Enrollment United States | 7 participants | 8 participants | 15 participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 6 Participants | 8 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 7 | 3 / 8 |
| other Total, other adverse events | 7 / 7 | 6 / 8 |
| serious Total, serious adverse events | 7 / 7 | 7 / 8 |
Outcome results
Primary
Durable Response Rate (DRR) (Cohorts 1 and 2)
Durable Response Rate (DRR) defined as the proportion of patients who achieved a confirmed complete or partial response (CR or PR) and maintained that response for at least 6 months.
Time frame: At 6 months
Population: one patient withdrew Cohort 2
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Metastatic or Locally Advanced Naive Small Cell Bladder Cancer | Durable Response Rate (DRR) (Cohorts 1 and 2) | 100 percentage of participants |
| Cohort 2: Small Cell or Neuroendocrine Prostate Cancer | Durable Response Rate (DRR) (Cohorts 1 and 2) | 66.7 percentage of participants |
Primary
Duration of Response (DOR) Per RECIST 1.1 (Cohorts 1 and 2)
Duration of Response (DOR) defined as the time from the first documented CR or PR until radiograph disease progression or Prostate-Specific Antigen (PSA) progression.
Time frame: From the first documented CR or PR up to 3 years
Population: one patient withdrew Cohort 2
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Metastatic or Locally Advanced Naive Small Cell Bladder Cancer | Duration of Response (DOR) Per RECIST 1.1 (Cohorts 1 and 2) | NA Months |
| Cohort 2: Small Cell or Neuroendocrine Prostate Cancer | Duration of Response (DOR) Per RECIST 1.1 (Cohorts 1 and 2) | 12.6 Months |
Primary
Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Cohorts 1 and 2)
Overall Response Rate (ORR) defined as patients by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 exhibited a complete or partial response (CR or PR). CR defined as disappearance of all target lesions. PR defined as \>= 30% decrease in sum of the longest diameter of target lesions. .
Time frame: Up to 3 years
Population: one patient withdrew Cohort 2
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Metastatic or Locally Advanced Naive Small Cell Bladder Cancer | Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Cohorts 1 and 2) | 0.43 proportion of participents |
| Cohort 2: Small Cell or Neuroendocrine Prostate Cancer | Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Cohorts 1 and 2) | 0.43 proportion of participents |
Primary
Percentage of Participants With Adverse Events Per Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (Cohorts 1 and 2)
Time frame: Up to 3 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Metastatic or Locally Advanced Naive Small Cell Bladder Cancer | Percentage of Participants With Adverse Events Per Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (Cohorts 1 and 2) | All Grades | 100 percentage of participants |
| Cohort 1: Metastatic or Locally Advanced Naive Small Cell Bladder Cancer | Percentage of Participants With Adverse Events Per Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (Cohorts 1 and 2) | Grade 3 or higher | 57 percentage of participants |
| Cohort 2: Small Cell or Neuroendocrine Prostate Cancer | Percentage of Participants With Adverse Events Per Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (Cohorts 1 and 2) | Grade 3 or higher | 25 percentage of participants |
| Cohort 2: Small Cell or Neuroendocrine Prostate Cancer | Percentage of Participants With Adverse Events Per Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (Cohorts 1 and 2) | All Grades | 75 percentage of participants |
Primary
Portion of Participants With Radiographic Progression-free Survival (rPFS) by Prostate Cancer Working Group 3 (PCWG3) at 12 and 24 Months (Cohort 2)
PCWG3 is specifically designed for prostate cancer and incorporates both soft tissue and bone response assessment. RECIST 1.1 is used for evaluating responses in solid tumors, while PCWG3 combines Response evaluation criteria in solid tumors (RECIST)1.1 for soft tissue assessment with specific criteria for bone scans. The PCWG3 response criteria was used to report the portion of participants with rPFS at their 12 and 24 month assessments.
Time frame: 12 months and 24 months.
Population: The Primary outcome of Radiographic PFS (rPFS) with response criteria based off Prostate Cancer Working Group 3 (PCWG3) only applies to Prostate cancer patients enrolled into cohort 2. This criteria does not apply to Bladder cancer patients that enrolled in Cohort 1.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 2: Small Cell or Neuroendocrine Prostate Cancer | Portion of Participants With Radiographic Progression-free Survival (rPFS) by Prostate Cancer Working Group 3 (PCWG3) at 12 and 24 Months (Cohort 2) | 12 Months | .43 proportion of participants |
| Cohort 2: Small Cell or Neuroendocrine Prostate Cancer | Portion of Participants With Radiographic Progression-free Survival (rPFS) by Prostate Cancer Working Group 3 (PCWG3) at 12 and 24 Months (Cohort 2) | 24 Months | 0.14 proportion of participants |
Primary
Proportion of Participants With Overall Survival of Cohort 1 and 2 at 12 and 24 Months
Overall Survival (OS) defined as the time from the first day of study treatment to the time of death from any cause.
Time frame: 12 months and 24 months.
Population: one patient withdrew Cohort 2
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Metastatic or Locally Advanced Naive Small Cell Bladder Cancer | Proportion of Participants With Overall Survival of Cohort 1 and 2 at 12 and 24 Months | 12 months | 0.86 Proportion of patients |
| Cohort 1: Metastatic or Locally Advanced Naive Small Cell Bladder Cancer | Proportion of Participants With Overall Survival of Cohort 1 and 2 at 12 and 24 Months | 24 months | 0.86 Proportion of patients |
| Cohort 2: Small Cell or Neuroendocrine Prostate Cancer | Proportion of Participants With Overall Survival of Cohort 1 and 2 at 12 and 24 Months | 12 months | 0.71 Proportion of patients |
| Cohort 2: Small Cell or Neuroendocrine Prostate Cancer | Proportion of Participants With Overall Survival of Cohort 1 and 2 at 12 and 24 Months | 24 months | 0.57 Proportion of patients |
Primary
Proportion of Participants With Progression Free Survival at 12 and 24 Months
Progression Free Survival (PFS) defined as the time from the first day of study treatment to first documented disease progression by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 as a 20% increase in the sum of the longest diameter of target lesions, a measurable increase in a non-target lesion, or the appearance of new lesion(s).
Time frame: 12 months and 24 months.
Population: Proportion of Participants with Progression Free Survival at 12 and 24 Months was measured using sample size of each cohort and incidence of events to provide confidence intervals.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Metastatic or Locally Advanced Naive Small Cell Bladder Cancer | Proportion of Participants With Progression Free Survival at 12 and 24 Months | 12 months | 0.86 Proportion of patients |
| Cohort 1: Metastatic or Locally Advanced Naive Small Cell Bladder Cancer | Proportion of Participants With Progression Free Survival at 12 and 24 Months | 24 months | 0.86 Proportion of patients |
| Cohort 2: Small Cell or Neuroendocrine Prostate Cancer | Proportion of Participants With Progression Free Survival at 12 and 24 Months | 12 months | .43 Proportion of patients |
| Cohort 2: Small Cell or Neuroendocrine Prostate Cancer | Proportion of Participants With Progression Free Survival at 12 and 24 Months | 24 months | 0.14 Proportion of patients |
Other Pre-specified
Percentage of Participants With Programmed Death-ligand 1 (PD-L1) Combined Positive Score (CPS) Greater Than 10, at 12 Months
Time frame: at 12 months
Population: PD-L1% (defined CPS\>10). combined positive score (CPS). CPS defined as number of PD-L1 staining cells in tumor, lymphocytes, and macrophages divided by total number viable tumor cells x 100.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Metastatic or Locally Advanced Naive Small Cell Bladder Cancer | Percentage of Participants With Programmed Death-ligand 1 (PD-L1) Combined Positive Score (CPS) Greater Than 10, at 12 Months | 42.8 Percentage of patients with (CPS) > 10 |
| Cohort 2: Small Cell or Neuroendocrine Prostate Cancer | Percentage of Participants With Programmed Death-ligand 1 (PD-L1) Combined Positive Score (CPS) Greater Than 10, at 12 Months | 37.5 Percentage of patients with (CPS) > 10 |