Prostatic Neoplasms
Conditions
Brief summary
The study will evaluate the safety, pharmacokinetics and pharmacodynamics of increasing doses of a vaccine-based immunotherapy regimen for patients with prostate cancer.
Interventions
BIOLOGICALPF-06755992
PF-06755992 will be administered on Day 1 of Cycles 1 and 2.
BIOLOGICALPF-06755990
PF-06755990 will be administered using a device on Day 29, 57 and 85 of each cycle.
DEVICETDS-IM Electroporation Device
TDS-IM electroporation device and associated supplies will be used for PF-06755990 administration
BIOLOGICALTremelimumab
PF-06753388 will be administered every 28 days.
BIOLOGICALPF-06801591
PF-06801591 will be administered every 28 days.
BIOLOGICALPF-06753512
Combination of adenovirus (AdC68) + plasmid DNA (pDNA) + tremelimumab
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histological or cytological diagnosis of prostate cancer * Adequate bone marrow, kidney and liver function * Hormone sensitive relapsing prostate cancer after definitive local therapy (biochemical relapse) OR * Failed prior therapy with a novel hormone (e.g. enzalutamide, abiraterone) with documented progressive disease (post-novel hormone therapy CRPC)
Exclusion criteria
* ECOG performance status greater than or equal to 2 * Concurrent immunotherapy for prostate cancer * History of or active autoimmune disorders (including but not limited to: myasthenia gravis, thyroiditis, pneumonitis, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, scleroderma) and other conditions that disorganize or alter the immune system. * History of inflammatory bowel disease. * Current use of any implanted electronic stimulation device * For biochemically relapsed patients, no concurrent use of ADT or orchiectomy and no known prior or current evidence of any metastatic involvement of distant organs * For post-novel hormone patients, no concurrent treatment with a secondary hormone (e.g. enzalutamide, abiraterone), no metastasis to the liver or brain
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With AEs Leading to Discontinuation or Dose Reduction | Baseline up to 6 months after EOT (52 months in maximum) | An AE was any untoward medical occurrence in a clinical investigation where participant administered a product; the event did not need to have a causal relationship with the treatment. |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline up to 6 months after End of Treatment (EOT; 52 months in maximum) | An AE was any untoward medical occurrence in a clinical investigation where participant administered a product; the event did not need to have a causal relationship with the treatment. A SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and non-serious AEs. |
| Number of Participants With AEs as Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) (Grade >= 3) | Baseline up to 6 months after EOT (52 months in maximum) | An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. Grades of AEs were defined by NCI CTCAE v 4.03. Grade 1=asymptomatic/mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2=minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activity of daily living (ADL); Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4=events with life-threatening consequences, urgent intervention indicated; Grade 5= death related to AE. Treatment-emergent adverse events occurred between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. |
| Number of Participants With Dose-Limiting Toxicities (DLTs) | The first 28 days following the first AdC68 vaccination (on Cycle 1 Day 1) | The following AEs occurring in the first 28 days following the first AdC68 vaccination and not related to disease/progression were DLTs: (a) hematologic (Cohorts 1A to 3A and Cohorts 6A to 9A): Grade 3 neutropenia lasting \>7 days, febrile neutropenia, Grade \>=3 neutropenic infection, Grade \>=3 thrombocytopenia, Grade \>=3 anemia lasting \>7 days, Grade \>=3 lymphopenia lasting \>14 days; (b) non-hematologic (all cohorts): Grade \>=3 laboratory abnormalities either associated with symptoms or associated with worsening of an existing condition or that suggested a new disease process or that required additional active management, Grade \>=3 toxicities, Grade 3 flu like symptoms lasting \>3 days, fever of \>40.0 degree Celsius lasting \>3 days. Other clinically important or persistent toxicities at discretion of investigator and Pfizer. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in T Cell Response to Prostate Stem Cell Antigen (PSCA) in Part A | At screening; Cycle 1: at Day 1, Day 15, Day 29, Day 43, Day 71; Cycle 2: at Day 1, Day 29, and Day 99; at the EOT visit, and 2, 4 and 6 months after EOT. | T cell response to PSCA was determined by assaying PBMC samples for cellular immune responses against PSCA antigens and was determined as the frequency of IFN-γ SFC/million PBMCs. Change from baseline at Cycle 1 Day 71 and at Cycle 2 Day 99 are presented here. |
| Change From Baseline in T Cell Response to Prostate Specific Membrane Antigen (PSMA) in Part A | At screening; Cycle 1: at Day 1, Day 15, Day 29, Day 43, Day 71; Cycle 2: at Day 1, Day 29, and Day 99; at the EOT visit, and 2, 4 and 6 months after EOT. | T cell response to PSMA was determined by assaying PBMC samples for cellular immune responses against PSMA antigens and was determined as the frequency of IFN-γ SFC/million PBMCs. Change from baseline at Cycle 1 Day 71 and at Cycle 2 Day 99 are presented here. |
| Maximum Observed Plasma Concentration (Cmax) of Tremelimumab in Part A | Cycle 1: at Day 1 pre-dose, any time between 48 to 120 hr, approximately 168 hr, 336 hr, and 504 hr, at pre-dose on Day 29, Day 57, and Day 85; Cycle 2: at pre-dose on Day 1 and Day 29; at EOT visit, and 2, 4 and 6 months after EOT. | Cmax was defined as the maximum observed plasma concentration. Blood samples (approximately 3 mL whole blood) to provide at least 1 mL of serum for measurement of tremelimumab PK analysis were collected. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tremelimumab in Part A | Cycle 1: at Day 1 pre-dose, any time between 48 to 120 hr, approximately 168 hr, 336 hr, and 504 hr, at pre-dose on Day 29, Day 57, and Day 85; Cycle 2: at pre-dose on Day 1 and Day 29; at EOT visit, and 2, 4 and 6 months after EOT. | Tmax was defined as the time to reach maximum observed plasma concentration. Blood samples (approximately 3 mL whole blood) to provide at least 1 mL of serum for measurement of tremelimumab PK analysis were collected. |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Tremelimumab in Part A | Cycle 1: at Day 1 pre-dose, any time between 48 to 120 hr, approximately 168 hr, 336 hr, and 504 hr, at pre-dose on Day 29, Day 57, and Day 85; Cycle 2: at pre-dose on Day 1 and Day 29; at EOT visit, and 2, 4 and 6 months after EOT. | AUClast was defined as the area under the curve from time zero to last quantifiable concentration. Blood samples (approximately 3 mL whole blood) to provide at least 1 mL of serum for measurement of tremelimumab PK analysis were collected. |
| Trough Concentrations (Ctrough) After Multiple Dosing of Tremelimumab | Pre-dose on Cycle 2 Day 1 | Pre-dose tremelimumab concentration on Cycle 2 Day 1 is presented here as Ctrough. Blood samples (approximately 3 mL whole blood) to provide at least 1 mL of serum for measurement of tremelimumab PK analysis were collected. Summary statistics of Ctrough were not calculated if number of observations above lower lit of quantification (NALQ)=0 or \<=3 participants had non-missing data. |
| Cmax of PF-06801591 in Part A | Cycle 1: at Day 1 pre-dose, any time between 48 to 120 hr, approximately 168 hr, 336 hr, and 504 hr, at pre-dose on Day 29, Day 57, and Day 85; Cycle 2: at pre-dose on Day 1 and Day 29; at EOT visit, and 2, 4 and 6 months after EOT. | Cmax was defined as the maximum observed plasma concentration. Blood samples (approximately 5 mL) to provide serum for the analysis of PF-06801591 concentrations were collected. |
| Tmax of PF-06801591 in Part A | Cycle 1: at Day 1 pre-dose, any time between 48 to 120 hr, approximately 168 hr, 336 hr, and 504 hr, at pre-dose on Day 29, Day 57, and Day 85; Cycle 2: at pre-dose on Day 1 and Day 29; at EOT visit, and 2, 4 and 6 months after EOT. | Tmax was defined as the time at which Cmax occurred. Blood samples (approximately 5 mL) to provide serum for the analysis of PF- 06801591 concentrations were collected. |
| AUClast of PF-06801591 in Part A | Cycle 1: at Day 1 pre-dose, any time between 48 to 120 hr, approximately 168 hr, 336 hr, and 504 hr, at pre-dose on Day 29, Day 57, and Day 85; Cycle 2: at pre-dose on Day 1 and Day 29; at EOT visit, and 2, 4 and 6 months after EOT. | AUClast was defined as the area under the curve from time zero to last quantifiable concentration. Blood samples (approximately 5 mL) to provide serum for the analysis of PF-06801591 concentrations were collected. The geometric mean and geometric coefficient of variation of AUClast for Cohort 9A were not presented because fewer than 3 participants had reportable parameter values. |
| Ctrough of PF-06801591 | Pre-dose on Cycle 2 Day 1 | Pre-dose PF-06801591 concentration on Cycle 2 Day 1 is presented here as Ctrough. Blood samples (approximately 3 mL whole blood) to provide at least 1 mL of serum for measurement of PF-06801591 PK analysis were collected. |
| Number of Participants With Anti-Drug Antibody (ADA) Against Tremelimumab | Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to tremelimumab dosing. | Blood samples (approximately 5 mL) to provide at least 1 mL of serum to detect ADA were collected from participants enrolled in to Cohorts 3A to 9A and Cohorts 1B to 5B. Participants were considered ADA-positive if sample titer (log10) \>=1.48; participants were considered ADA-negative if sample titer (log10) \<1.48. |
| Titer of Treatment-Induced ADA Against Tremelimumab | Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to tremelimumab dosing. | Treatment-induced ADA was defined as baseline titer missing or negative and participant had \>=1 post-treatment positive titer. Blood samples (approximately 5 mL) to provide at least 1 mL of serum to detect ADA were collected from participants enrolled in to Cohorts 3A to 9A and Cohorts 1B to 5B. |
| Number of Participants With Neutralizing Antibody (NAb) Against Tremelimumab | Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to tremelimumab dosing. | Only those samples tested positive for ADA were to be further tested for Nab. Blood samples (approximately 5 mL) to provide at least 1 mL of serum to detect NAb were collected from participants enrolled in to Cohorts 3A to 9A and Cohorts 1B to 5B. Nab against tremelimumab was not examined due to business reason. |
| Titer of Treatment-Induced NAb Against Tremelimumab | Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to tremelimumab dosing. | Only those samples tested positive for ADA were to be further tested for Nab. Blood samples (approximately 5 mL) to provide at least 1 mL of serum to detect NAb were collected from participants enrolled in to Cohorts 3A to 9A and Cohorts 1B to 5B. Nab against tremelimumab was not examined due to business reason. |
| Number of Participants With ADA Against PF-06801591 | Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to PF-06801591 dosing. | Participants were considered ADA-positive if sample titer (log10) \>=99; Participants were considered ADA-negative if sample titer (log10) \<99. Blood samples (approximately 5 mL) to provide at least 1 mL of serum for detection of ADA against PF-06801591 were collected from participants enrolled in Cohorts 6A to 9A and Cohorts 3B and 5B. |
| Titer of Treatment-Induced ADA Against PF-06801591 | Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to PF-06801591 dosing. | Treatment-induced ADA was defined as baseline titer missing or negative and participant had \>=1 post-treatment positive titer. Blood samples (approximately 5 mL) to provide at least 1 mL of serum for detection of ADA against PF-06801591 were collected from participants enrolled in Cohorts 6A to 9A and Cohorts 3B and 5B. |
| Number of Participants With NAb Against PF-06801591 | Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to PF-06801591 dosing. | Only those samples tested positive for ADA were to be further tested for Nab. Blood samples (approximately 5 mL) to provide at least 1 mL of serum for detection of NAb against PF-06801591 were collected from participants enrolled in Cohorts 6A to 9A and Cohorts 3B and 5B. Nab against PF-06801591 was not examined due to business reason. |
| Titer of Treatment-Induced NAb Against PF-06801591 | Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to PF-06801591 dosing. | Only those samples tested positive for ADA were to be further tested for Nab. Blood samples (approximately 5 mL) to provide at least 1 mL of serum for detection of NAb against PF-06801591 were collected from participants enrolled in Cohorts 6A to 9A and Cohorts 3B and 5B. Nab against PF-06801591 was not examined due to business reason. |
| Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Cohort 7A and 3B Combined and All mCRPC Patients | Baseline up to 6 months after EOT (52 months in maximum) | ORR was defined as the percentage of participants with best overall response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST v1.1. Per RECIST v1.1: CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm) and no new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease and no new lesions. |
| Duration of Response (DOR) by RECIST v1.1 in Cohort 7A and 3B Combined and All mCRPC Patients | Baseline up to 6 months after EOT (52 months in maximum) | DOR was defined as the time from first documentation of confirmed CR or PR to date of first documentation of progressive disease (PD) or death due to any cause according to RECIST v1.1. Per RECIST v1.1: CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm) and no new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all measurable target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease and no new lesions. PD was defined as \>=20% increase in the sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm. Unequivocal progression of pre existing lesions for non-target disease. |
| Immune-Related Confirmed ORR by Immune Related Response Evaluation Criteria in Solid Tumors Version 1.1 (irRECIST v1.1) in Cohort 7A and 3B Combined and All mCRPC Patients | Baseline up to 6 months after EOT (52 months in maximum) | Immune-related confirmed ORR was defined as the percentage of participants with objective response based assessment of confirmed immune related complete response (irCR) or confirmed immune related partial response (irPR) according to irRECIST v1.1. Per irRECIST v1.1: irCR was defined as complete disappearance of all lesions and no new lesions. All measurable lymph nodes also must have a reduction in short axis to \<10 mm. irPR was defined as sum of the diameters (longest for non nodal lesions, shortest for nodal lesions) of target and new measurable lesions must decrease \>=30%. |
| Immune-Related Confirmed DOR by irRECIST v1.1 in Cohort 7A and 3B Combined and All mCRPC Patients | Baseline up to 6 months after EOT (52 months in maximum) | Immune-related confirmed DOR was defined as the time from first documentation of confirmed irCR or confirmed irPR to date of first documentation of immune related progressive disease (irPD) or death due to any cause according to irRECIST. Per irRECIST v1.1: irCR was defined as complete disappearance of all lesions and no new lesions. All measurable lymph nodes also must have a reduction in short axis to \<10 mm. irPR was defined as sum of the diameters (longest for non nodal lesions, shortest for nodal lesions) of target and new measurable lesions must decrease \>=30%. irPD was defined as sum of the diameters of target and new measurable lesions must increase \>=20%, confirmed by a repeat, consecutive observation at least 4 weeks from the date first documented. |
| Number of Patients With Bone Progression Per Prostrate Cancer Working Group 3 (PCWG3) Criteria in Cohort 7A and 3B Combined | Baseline up to 6 months after EOT (52 months in maximum) | Number of participants with bone progression per Prostate Cancer Clinical Trials Working Group 3 (PCWG3). Per PCWG3, progressing disease on bone scan was considered when at least two new lesions relative to the first post treatment scan was confirmed on a subsequent scan (6 or more weeks later). |
| Radiographic Progression Free Survival (rPFS) Per RECIST v1.1 in Cohort 7A and 3B Combined , All mCRPC Patients, Cohort 1B, and Cohort 5B | Baseline up to 6 months after EOT (52 months in maximum) | Radiographic Progression Free Survival (rPFS) per RECIST v1.1. rPFS was defined as the time from first dose of study treatment to date of first documentation of radiographic PD or death due to any cause, whichever occurs first. Per RECIST v1.1, PD was defined as \>=20% increase in the sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm. Unequivocal progression of pre existing lesions for non-target disease. The Kaplan Meier estimate of median rPFS was presented here. |
| Number of Participants Achieving Central PSA Response >= 50% Decline From Baseline (PSA-50) in Part B | At screening; Cycle 1 and 2: at Day 1, Day 29, Day 57, and Day 85; at the EOT visit, and 1, 2, 4 and 6 months after EOT. | PSA-50 response rate was defined as the proportion of patients whose on-study PSA declined from baseline by at least 50% at two consecutive measurements at least 3 weeks apart, prior to other systematic anti-cancer therapy. |
| Duration of PSA-50 Response in Part B | Days 1, 29, 57 of Cycle 1 and Cycle 2. | Duration of PSA-50 response was defined as the period from the first measurement when PSA-50 response was achieved to the measurement when PSA-50 response no longer held. |
| Baseline for PSA in Part B | At screening and Cycle 1 Day 1. | PSA Baseline is defined as the most recent non-missing value prior to dosing. |
| Baseline for PSA Doubling Time (PSADT) in Part B | At screening and Cycle 1 Day 1. | PSADT was defined as the natural log of 2 divided by the slope of the linear regression line of the natural log of PSA against time in month. Baseline has been calculated from the PSA values at screening and C1D1. |
| Baseline for PSA Slope in Part B | At screening and Cycle 1 Day 1. | PSA slope was defined as the slope of the linear regression line of natural log of PSA against time in month. Baseline has been calculated from the PSA values at screening and C1D1. |
| Baseline for PSA Velocity in Part B | At screening and Cycle 1 Day 1. | PSA velocity was defined as the slope of the linear regression line of PSA against time in month. Baseline has been calculated from the PSA values at screening and C1D1. |
| Change in PSADT at Post-Treatment Visit From Baseline in Part B | At screening; Cycle 1 and 2: at Day 1, Day 29, Day 57, and Day 85; at the EOT visit, and 1, 2, 4 and 6 months after EOT. | PSADT was defined as the natural log of 2 divided by the slope of the linear regression line of the natural log of PSA against time in month. PSADT at the post-treatment visit was calculated from C1D1 and all post-treatment PSA values. |
| Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4) | Baseline up to 6 months after EOT (52 months in maximum) | Laboratory abnormalities were graded per NCI CTCAE version 4.03 (Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated) and those with at least 1 participant are presented here. Hematology parameters included hemoglobin, platelets, white blood cell count, neutrophils, eosinophils, monocytes, basophils and lymphocytes. |
| Change in PSA Velocity at Post-Treatment Visit From Baseline in Part B | At screening; Cycle 1 and 2: at Day 1, Day 29, Day 57, and Day 85; at the EOT visit, and 1, 2, 4 and 6 months after EOT. | PSA velocity was defined as the slope of the linear regression line of PSA against time in month. PSA velocity at the post-treatment visit was calculated from C1D1 and all post-treatment PSA values. |
| Change in PSA Slope at Post-Treatment Visit From Baseline in Part B | At screening; Cycle 1 and 2: at Day 1, Day 29, Day 57, and Day 85; at the EOT visit, and 1, 2, 4 and 6 months after EOT. | PSA slope was defined as the slope of the linear regression line of natural log of PSA against time in month. PSA slope at the post-treatment visit was calculated from C1D1 and all post-treatment PSA values. |
| Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Baseline up to 6 months after EOT (52 months in maximum) | Laboratory abnormalities were graded per NCI CTCAE version 4.03 (Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated) and those with at least 1 participant are presented here. Chemistry parameters included aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, sodium, potassium, magnesium, chloride, total calcium, total bilirubin, blood urea nitrogen (or urea), creatinine, uric acid, glucose, albumin, phosphorous or phosphate, lactate dehydrogenase, lipase, bicarbonate or carbon dioxide, total protein, TSH (if abnormal, reflex free T4 and free T3). |
| Number of Participants With Laboratory Abnormalities in Urinalysis (Grade 3 or 4) | Baseline up to 6 months after EOT (52 months in maximum) | Laboratory abnormalities were graded per NCI CTCAE version 4.03 (Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated) and those with at least 1 participant are presented here. Urine parameters included urine protein and urine blood. |
| Change From Baseline in T Cell Response to Prostate Specific Antigen (PSA) in Part A | At screening; Cycle 1: at Day 1, Day 15, Day 29, Day 43, Day 71; Cycle 2: at Day 1, Day 29, and Day 99; at the EOT visit, and 2, 4 and 6 months after EOT. | T cell response to PSA was determined by assaying peripheral blood mononuclear cell (PBMC) samples for cellular immune responses against PSA antigens and was determined as the frequency of interferon-gamma (IFN-γ) spot forming cells (SFC)/million PBMCs. Change from baseline at Cycle 1 Day 71 and at Cycle 2 Day 99 are presented here. |
Countries
United States
Participant flow
Pre-assignment details
A total of 123 participants were screened and 91 of them were assigned and treated in this study.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1A: AdC68 4x10^11 VP + pDNA 5 mg Participants with mCRPC in Cohort 1A received 2 repeated cycles (16 weeks each) of treatment, including AdC68 4x10\^11 VP IM on Day 1 of Cycle 1 and 2, and pDNA 5 mg IM on Day 29, 57, and 85 of Cycle 1 and 2. Following the 2 cycles, participants in Cohort 1A entered the maintenance phase and received pDNA 5 mg every 2 months starting from Month 10, as long as there was clinical benefit. | 3 |
| Cohort 2A: AdC68 6x10^11 VP + pDNA 5 mg Participants with mCRPC in Cohort 2A received 2 repeated cycles (16 weeks each) of treatment, including AdC68 6x10\^11 VP IM on Day 1 of Cycle 1 and 2, and pDNA 5 mg IM on Day 29, 57, and 85 of Cycle 1 and 2. Following the 2 cycles, participants in Cohort 2A entered the maintenance phase and received pDNA 5 mg every 2 months starting from Month 10, as long as there was clinical benefit. | 4 |
| Cohort 3A: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg Participants with mCRPC in Cohort 3A received 2 repeated cycles (16 weeks each) of treatment, including AdC68 6x10\^11 VP IM on Day 1 of Cycle 1 and 2, and pDNA 5 mg IM on Day 29, 57, and 85 of Cycle 1 and 2. On Day 1, 29, 57, and 85 of Cycle 1 and 2, tremelimumab 80 mg was also administered SC after the AdC68 or pDNA administration. Following the 2 cycles, participants in Cohort 3A entered the maintenance phase and received pDNA 5 mg and tremelimumab 80 mg every 2 months starting from Month 10, as long as there was clinical benefit. | 6 |
| Cohort 6A: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg Participants with mCRPC in Cohort 6A received 2 repeated cycles (16 weeks each) of treatment, including AdC68 6x10\^11 VP IM on Day 1 of Cycle 1 and 2, and pDNA 5 mg IM on Day 29, 57, and 85 of Cycle 1 and 2. On Day 1, 29, 57, and 85 of Cycle 1 and 2, tremelimumab 80 mg and PF-06801591 130 mg were also administered SC after the AdC68 or pDNA administration. Following the 2 cycles, participants in Cohort 6A entered the maintenance phase and received PF-06801591 130 mg every month starting from Month 9, as well as pDNA 5 mg and tremelimumab 80 mg every 2 months starting from Month 10, as long as there was clinical benefit. | 8 |
| Cohort 7A: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 300 mg Participants with mCRPC in Cohort 7A received 2 repeated cycles (16 weeks each) of treatment, including AdC68 6x10\^11 VP IM on Day 1 of Cycle 1 and 2, and pDNA 5 mg IM on Day 29, 57, and 85 of Cycle 1 and 2. On Day 1, 29, 57, and 85 of Cycle 1 and 2, tremelimumab 80 mg and PF-06801591 300 mg were also administered SC after the AdC68 or pDNA administration. Following the 2 cycles, participants in Cohort 7A entered the maintenance phase and received PF-06801591 300 mg every month starting from Month 9, as well as pDNA 5 mg and tremelimumab 80 mg every 2 months starting from Month 10, as long as there was clinical benefit. | 14 |
| Cohort 9A: AdC68 6x10^11 VP + pDNA 5 mg + Treme 40 mg + PF-06801591 130 mg Participants with mCRPC in Cohort 9A received 2 repeated cycles (16 weeks each) of treatment, including AdC68 6x10\^11 VP IM on Day 1 of Cycle 1 and 2, and pDNA 5 mg IM on Day 29, 57, and 85 of Cycle 1 and 2. On Day 1, 29, 57, and 85 of Cycle 1 and 2, tremelimumab 40 mg and PF-06801591 130 mg were also administered SC after the AdC68 or pDNA administration. Following the 2 cycles, participants in Cohort 9A entered the maintenance phase and received PF-06801591 130 mg every month starting from Month 9, as well as pDNA 5 mg and tremelimumab 40 mg every 2 months starting from Month 10, as long as there was clinical benefit. | 3 |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg Participants with BCR of prostate cancer in Cohort 1B received 2 repeated cycles (16 weeks each) of treatment, including AdC68 6x10\^11 VP IM on Day 1 of Cycle 1 and 2, and pDNA 5 mg IM on Day 29, 57, and 85 of Cycle 1 and 2. On Day 1, 29, 57, and 85 of Cycle 1 and 2, tremelimumab 80 mg was also administered SC after the AdC68 or pDNA administration. Following the 2 cycles, participants in Cohort 1B entered the maintenance phase and received pDNA 5 mg and tremelimumab 80 mg every 2 months starting from Month 10, as long as there was clinical benefit. | 20 |
| Cohort 3B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 300 mg Participants with mCRPC in Cohort 3B received 2 repeated cycles (16 weeks each) of treatment, including AdC68 6x10\^11 VP IM on Day 1 of Cycle 1 and 2, and pDNA 5 mg IM on Day 29, 57, and 85 of Cycle 1 and 2. On Day 1, 29, 57, and 85 of Cycle 1 and 2, tremelimumab 80 mg and PF-06801591 300 mg were also administered SC after the AdC68 or pDNA administration. Following the 2 cycles, participants in Cohort 3B entered the maintenance phase and received PF-06801591 300 mg every month starting from Month 9, as well as pDNA 5 mg and tremelimumab 80 mg every 2 months starting from Month 10, as long as there was clinical benefit. | 18 |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg Participants with BCR of prostate cancer in Cohort 5B received 2 repeated cycles (16 weeks each) of treatment, including AdC68 6x10\^11 VP IM on Day 1 of Cycle 1 and 2, and pDNA 5 mg IM on Day 29, 57, and 85 of Cycle 1 and 2. On Day 1, 29, 57, and 85 of Cycle 1 and 2, tremelimumab 80 mg and PF-06801591 130 mg were also administered SC after the AdC68 or pDNA administration. Following the 2 cycles, participants in Cohort 5B entered the maintenance phase and received PF-06801591 130 mg every month starting from Month 9, as well as pDNA 5 mg and tremelimumab 80 mg every 2 months starting from Month 10, as long as there was clinical benefit. | 15 |
| Total | 91 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 0 | 1 | 2 | 0 | 0 | 2 | 1 |
| Overall Study | Not reported | 0 | 0 | 0 | 1 | 3 | 1 | 0 | 5 | 2 |
| Overall Study | Participant refused further follow-up | 1 | 1 | 2 | 3 | 4 | 0 | 3 | 4 | 3 |
| Overall Study | Study terminated by sponsor | 0 | 0 | 1 | 0 | 0 | 0 | 5 | 2 | 0 |
Baseline characteristics
| Characteristic | Cohort 1A: AdC68 4x10^11 VP + pDNA 5 mg | Cohort 2A: AdC68 6x10^11 VP + pDNA 5 mg | Cohort 3A: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Cohort 6A: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Cohort 7A: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 300 mg | Cohort 9A: AdC68 6x10^11 VP + pDNA 5 mg + Treme 40 mg + PF-06801591 130 mg | Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Cohort 3B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 300 mg | Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 4 Participants | 4 Participants | 4 Participants | 11 Participants | 3 Participants | 14 Participants | 15 Participants | 11 Participants | 69 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 2 Participants | 4 Participants | 3 Participants | 0 Participants | 6 Participants | 3 Participants | 4 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 4 Participants | 6 Participants | 8 Participants | 14 Participants | 3 Participants | 18 Participants | 17 Participants | 15 Participants | 88 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 4 Participants | 2 Participants | 11 Participants |
| Race/Ethnicity, Customized White | 3 Participants | 4 Participants | 6 Participants | 7 Participants | 12 Participants | 2 Participants | 19 Participants | 13 Participants | 13 Participants | 79 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 6 Participants | 8 Participants | 14 Participants | 3 Participants | 20 Participants | 18 Participants | 15 Participants | 91 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 4 | 0 / 6 | 1 / 8 | 2 / 14 | 0 / 3 | 0 / 20 | 2 / 18 | 1 / 15 |
| other Total, other adverse events | 3 / 3 | 4 / 4 | 5 / 6 | 8 / 8 | 14 / 14 | 3 / 3 | 20 / 20 | 18 / 18 | 15 / 15 |
| serious Total, serious adverse events | 0 / 3 | 0 / 4 | 2 / 6 | 2 / 8 | 4 / 14 | 1 / 3 | 2 / 20 | 7 / 18 | 6 / 15 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a clinical investigation where participant administered a product; the event did not need to have a causal relationship with the treatment. A SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and non-serious AEs.
Time frame: Baseline up to 6 months after End of Treatment (EOT; 52 months in maximum)
Population: Safety analysis set: all enrolled participants who received at least one dose of one of the components of the regimen. For this outcome measure, participants are grouped by disease type and treatment, as follows: Cohort All mCRPC Patients (all mCRPC participants), Cohort 1B (BCR with 1 immune checkpoint inhibitor \[ICI\]), Cohort 5B (BCR with 2 ICIs), and Cohort 7A and 3B Combined (mCRPC at recommended Phase 2 dose \[RP2D\] dose).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort All mCRPC Patients | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with all-causality AEs | 55 Participants |
| Cohort All mCRPC Patients | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with treatment-related AEs | 51 Participants |
| Cohort All mCRPC Patients | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with all-causality SAEs | 16 Participants |
| Cohort All mCRPC Patients | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with treatment-related SAEs | 11 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with treatment-related AEs | 19 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with all-causality SAEs | 2 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with treatment-related SAEs | 0 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with all-causality AEs | 20 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with all-causality SAEs | 6 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with treatment-related AEs | 15 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with treatment-related SAEs | 6 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with all-causality AEs | 15 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with treatment-related SAEs | 9 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with treatment-related AEs | 31 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with all-causality AEs | 32 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with all-causality SAEs | 11 Participants |
Primary
Number of Participants With AEs as Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) (Grade >= 3)
An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. Grades of AEs were defined by NCI CTCAE v 4.03. Grade 1=asymptomatic/mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2=minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activity of daily living (ADL); Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4=events with life-threatening consequences, urgent intervention indicated; Grade 5= death related to AE. Treatment-emergent adverse events occurred between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Time frame: Baseline up to 6 months after EOT (52 months in maximum)
Population: Safety analysis set: all enrolled participants who received at least one dose of one of the components of the regimen. For this outcome measure, participants are grouped by disease type and treatment, as follows: Cohort All mCRPC Patients (all mCRPC participants), Cohort 1B (BCR with 1 immune checkpoint inhibitor \[ICI\]), Cohort 5B (BCR with 2 ICIs), and Cohort 7A and 3B Combined (mCRPC at recommended Phase 2 dose \[RP2D\] dose).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort All mCRPC Patients | Number of Participants With AEs as Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) (Grade >= 3) | Grade 3 or Grade 4 (all-causality) | 33 Participants |
| Cohort All mCRPC Patients | Number of Participants With AEs as Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) (Grade >= 3) | Grade 3 or Grade 4 (treatment-related) | 23 Participants |
| Cohort All mCRPC Patients | Number of Participants With AEs as Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) (Grade >= 3) | Grade 5 (all-causality) | 4 Participants |
| Cohort All mCRPC Patients | Number of Participants With AEs as Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) (Grade >= 3) | Grade 5 (treatment-related) | 1 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With AEs as Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) (Grade >= 3) | Grade 3 or Grade 4 (treatment-related) | 6 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With AEs as Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) (Grade >= 3) | Grade 5 (all-causality) | 0 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With AEs as Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) (Grade >= 3) | Grade 5 (treatment-related) | 0 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With AEs as Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) (Grade >= 3) | Grade 3 or Grade 4 (all-causality) | 10 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With AEs as Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) (Grade >= 3) | Grade 5 (all-causality) | 1 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With AEs as Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) (Grade >= 3) | Grade 3 or Grade 4 (treatment-related) | 10 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With AEs as Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) (Grade >= 3) | Grade 5 (treatment-related) | 1 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With AEs as Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) (Grade >= 3) | Grade 3 or Grade 4 (all-causality) | 11 Participants |
| Cohort 7A and 3B Combined | Number of Participants With AEs as Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) (Grade >= 3) | Grade 5 (treatment-related) | 0 Participants |
| Cohort 7A and 3B Combined | Number of Participants With AEs as Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) (Grade >= 3) | Grade 3 or Grade 4 (treatment-related) | 17 Participants |
| Cohort 7A and 3B Combined | Number of Participants With AEs as Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) (Grade >= 3) | Grade 3 or Grade 4 (all-causality) | 21 Participants |
| Cohort 7A and 3B Combined | Number of Participants With AEs as Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) (Grade >= 3) | Grade 5 (all-causality) | 3 Participants |
Primary
Number of Participants With AEs Leading to Discontinuation or Dose Reduction
An AE was any untoward medical occurrence in a clinical investigation where participant administered a product; the event did not need to have a causal relationship with the treatment.
Time frame: Baseline up to 6 months after EOT (52 months in maximum)
Population: Safety analysis set: all enrolled participants who received at least one dose of one of the components of the regimen. or this outcome measure, participants are grouped by disease type and treatment, as follows: Cohort All mCRPC Patients (all mCRPC participants), Cohort 1B (BCR with 1 immune checkpoint inhibitor \[ICI\]), Cohort 5B (BCR with 2 ICIs), and Cohort 7A and 3B Combined (mCRPC at recommended Phase 2 dose \[RP2D\] dose).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort All mCRPC Patients | Number of Participants With AEs Leading to Discontinuation or Dose Reduction | Number of participants with permanent discontinuations | 16 Participants |
| Cohort All mCRPC Patients | Number of Participants With AEs Leading to Discontinuation or Dose Reduction | Number of participants with dose reductions | 0 Participants |
| Cohort All mCRPC Patients | Number of Participants With AEs Leading to Discontinuation or Dose Reduction | Number of participants with temporary discontinuations | 17 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With AEs Leading to Discontinuation or Dose Reduction | Number of participants with permanent discontinuations | 1 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With AEs Leading to Discontinuation or Dose Reduction | Number of participants with dose reductions | 1 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With AEs Leading to Discontinuation or Dose Reduction | Number of participants with temporary discontinuations | 5 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With AEs Leading to Discontinuation or Dose Reduction | Number of participants with permanent discontinuations | 10 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With AEs Leading to Discontinuation or Dose Reduction | Number of participants with temporary discontinuations | 5 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With AEs Leading to Discontinuation or Dose Reduction | Number of participants with dose reductions | 0 Participants |
| Cohort 7A and 3B Combined | Number of Participants With AEs Leading to Discontinuation or Dose Reduction | Number of participants with permanent discontinuations | 11 Participants |
| Cohort 7A and 3B Combined | Number of Participants With AEs Leading to Discontinuation or Dose Reduction | Number of participants with dose reductions | 0 Participants |
| Cohort 7A and 3B Combined | Number of Participants With AEs Leading to Discontinuation or Dose Reduction | Number of participants with temporary discontinuations | 9 Participants |
Primary
Number of Participants With Dose-Limiting Toxicities (DLTs)
The following AEs occurring in the first 28 days following the first AdC68 vaccination and not related to disease/progression were DLTs: (a) hematologic (Cohorts 1A to 3A and Cohorts 6A to 9A): Grade 3 neutropenia lasting \>7 days, febrile neutropenia, Grade \>=3 neutropenic infection, Grade \>=3 thrombocytopenia, Grade \>=3 anemia lasting \>7 days, Grade \>=3 lymphopenia lasting \>14 days; (b) non-hematologic (all cohorts): Grade \>=3 laboratory abnormalities either associated with symptoms or associated with worsening of an existing condition or that suggested a new disease process or that required additional active management, Grade \>=3 toxicities, Grade 3 flu like symptoms lasting \>3 days, fever of \>40.0 degree Celsius lasting \>3 days. Other clinically important or persistent toxicities at discretion of investigator and Pfizer.
Time frame: The first 28 days following the first AdC68 vaccination (on Cycle 1 Day 1)
Population: Per protocol analysis set: all enrolled participants who received at least one dose of all assigned regimen components administered on Cycle 1 Day 1 and did not have major protocol deviations during the 28 days after the first vaccination. For this outcome measure, participants are grouped by disease type and treatment, as follows: Cohort All mCRPC Patients (all mCRPC participants), Cohort 1B (BCR with 1 ICI), Cohort 5B (BCR with 2 ICIs), and Cohort 7A and 3B Combined (mCRPC at RP2D dose).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort All mCRPC Patients | Number of Participants With Dose-Limiting Toxicities (DLTs) | 1 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Tremelimumab in Part A
AUClast was defined as the area under the curve from time zero to last quantifiable concentration. Blood samples (approximately 3 mL whole blood) to provide at least 1 mL of serum for measurement of tremelimumab PK analysis were collected.
Time frame: Cycle 1: at Day 1 pre-dose, any time between 48 to 120 hr, approximately 168 hr, 336 hr, and 504 hr, at pre-dose on Day 29, Day 57, and Day 85; Cycle 2: at pre-dose on Day 1 and Day 29; at EOT visit, and 2, 4 and 6 months after EOT.
Population: All enrolled participants treated in Part A who had sufficient information to estimate at least 1 of the PK parameters of interest and who had no major protocol deviations influencing the PK assessment. Participants in Part 1 Cohort 3A, 6A, 7A, and 9A were treated with tremelimumab, thus included in this outcome measure. Summary statistics for Cohort 6A, 7A, and 9A are not presented since no participants had reportable parameter values.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort All mCRPC Patients | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Tremelimumab in Part A | 2423000 ng*hr/mL | Geometric Coefficient of Variation 34 |
Secondary
AUClast of PF-06801591 in Part A
AUClast was defined as the area under the curve from time zero to last quantifiable concentration. Blood samples (approximately 5 mL) to provide serum for the analysis of PF-06801591 concentrations were collected. The geometric mean and geometric coefficient of variation of AUClast for Cohort 9A were not presented because fewer than 3 participants had reportable parameter values.
Time frame: Cycle 1: at Day 1 pre-dose, any time between 48 to 120 hr, approximately 168 hr, 336 hr, and 504 hr, at pre-dose on Day 29, Day 57, and Day 85; Cycle 2: at pre-dose on Day 1 and Day 29; at EOT visit, and 2, 4 and 6 months after EOT.
Population: All enrolled participants treated in Part A who had sufficient information to estimate at least 1 of the PK parameters of interest and who had no major protocol deviations influencing the PK assessment. Participants in Part 1 Cohort 6A, 7A, and 9A were treated with PF-06801591, thus included in this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort All mCRPC Patients | AUClast of PF-06801591 in Part A | 4095000 ng*hr/mL | Geometric Coefficient of Variation 43 |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | AUClast of PF-06801591 in Part A | 10370000 ng*hr/mL | Geometric Coefficient of Variation 42 |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | AUClast of PF-06801591 in Part A | NA ng*hr/mL | — |
Secondary
Baseline for PSA Doubling Time (PSADT) in Part B
PSADT was defined as the natural log of 2 divided by the slope of the linear regression line of the natural log of PSA against time in month. Baseline has been calculated from the PSA values at screening and C1D1.
Time frame: At screening and Cycle 1 Day 1.
Population: All enrolled participants in Part B who received at least one dose of all assigned regimen components administered on Cycle 1 Day 1 of treatment and must have at least 1 valid and determinate assay result related to the proposed analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort All mCRPC Patients | Baseline for PSA Doubling Time (PSADT) in Part B | 1.768 Months |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Baseline for PSA Doubling Time (PSADT) in Part B | 1.169 Months |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Baseline for PSA Doubling Time (PSADT) in Part B | 1.615 Months |
Secondary
Baseline for PSA in Part B
PSA Baseline is defined as the most recent non-missing value prior to dosing.
Time frame: At screening and Cycle 1 Day 1.
Population: All enrolled participants in Part B who received at least one dose of one of the components of the regimen.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort All mCRPC Patients | Baseline for PSA in Part B | Central PSA | 3.05 ng/ml |
| Cohort All mCRPC Patients | Baseline for PSA in Part B | Local PSA | 3.050 ng/ml |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Baseline for PSA in Part B | Central PSA | 33.45 ng/ml |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Baseline for PSA in Part B | Local PSA | 37.150 ng/ml |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Baseline for PSA in Part B | Central PSA | 2.10 ng/ml |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Baseline for PSA in Part B | Local PSA | 2.080 ng/ml |
Secondary
Baseline for PSA Slope in Part B
PSA slope was defined as the slope of the linear regression line of natural log of PSA against time in month. Baseline has been calculated from the PSA values at screening and C1D1.
Time frame: At screening and Cycle 1 Day 1.
Population: All enrolled participants in Part B who received at least one dose of all assigned regimen components administered on Cycle 1 Day 1 of treatment and must have at least 1 valid and determinate assay result related to the proposed analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort All mCRPC Patients | Baseline for PSA Slope in Part B | 0.178 Ratio |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Baseline for PSA Slope in Part B | 0.205 Ratio |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Baseline for PSA Slope in Part B | 0.138 Ratio |
Secondary
Baseline for PSA Velocity in Part B
PSA velocity was defined as the slope of the linear regression line of PSA against time in month. Baseline has been calculated from the PSA values at screening and C1D1.
Time frame: At screening and Cycle 1 Day 1.
Population: All enrolled participants in Part B who received at least one dose of all assigned regimen components administered on Cycle 1 Day 1 of treatment and must have at least 1 valid and determinate assay result related to the proposed analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort All mCRPC Patients | Baseline for PSA Velocity in Part B | 0.558 ng/ml/month |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Baseline for PSA Velocity in Part B | 3.629 ng/ml/month |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Baseline for PSA Velocity in Part B | 0.109 ng/ml/month |
Secondary
Change From Baseline in T Cell Response to Prostate Specific Antigen (PSA) in Part A
T cell response to PSA was determined by assaying peripheral blood mononuclear cell (PBMC) samples for cellular immune responses against PSA antigens and was determined as the frequency of interferon-gamma (IFN-γ) spot forming cells (SFC)/million PBMCs. Change from baseline at Cycle 1 Day 71 and at Cycle 2 Day 99 are presented here.
Time frame: At screening; Cycle 1: at Day 1, Day 15, Day 29, Day 43, Day 71; Cycle 2: at Day 1, Day 29, and Day 99; at the EOT visit, and 2, 4 and 6 months after EOT.
Population: All enrolled participants in Part A who received at least one dose of all assigned regimen components administered on Cycle 1 Day 1 of treatment and must have at least 1 valid and determinate assay result related to the proposed analysis. Number of Participants Analyzed = number of participants evaluable for this OM; Number Analyzed = number of participants evaluable for this OM at the time point specified.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort All mCRPC Patients | Change From Baseline in T Cell Response to Prostate Specific Antigen (PSA) in Part A | Cycle 2 Day 1 Compared With Cycle 2 Day 99 | NA SFC/10^6 PBMCS | — |
| Cohort All mCRPC Patients | Change From Baseline in T Cell Response to Prostate Specific Antigen (PSA) in Part A | Cycle 1 Day 1 Compared With Cycle 1 Day 71 | 2.83 SFC/10^6 PBMCS | Standard Deviation 4.907 |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Change From Baseline in T Cell Response to Prostate Specific Antigen (PSA) in Part A | Cycle 2 Day 1 Compared With Cycle 2 Day 99 | 5.50 SFC/10^6 PBMCS | Standard Deviation 9.526 |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Change From Baseline in T Cell Response to Prostate Specific Antigen (PSA) in Part A | Cycle 1 Day 1 Compared With Cycle 1 Day 71 | 4.17 SFC/10^6 PBMCS | Standard Deviation 7.217 |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Change From Baseline in T Cell Response to Prostate Specific Antigen (PSA) in Part A | Cycle 2 Day 1 Compared With Cycle 2 Day 99 | NA SFC/10^6 PBMCS | — |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Change From Baseline in T Cell Response to Prostate Specific Antigen (PSA) in Part A | Cycle 1 Day 1 Compared With Cycle 1 Day 71 | 1.70 SFC/10^6 PBMCS | Standard Deviation 3.801 |
| Cohort 7A and 3B Combined | Change From Baseline in T Cell Response to Prostate Specific Antigen (PSA) in Part A | Cycle 1 Day 1 Compared With Cycle 1 Day 71 | NA SFC/10^6 PBMCS | — |
| Cohort 7A: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 300 mg | Change From Baseline in T Cell Response to Prostate Specific Antigen (PSA) in Part A | Cycle 1 Day 1 Compared With Cycle 1 Day 71 | 24.25 SFC/10^6 PBMCS | Standard Deviation 34.295 |
| Cohort 9A: AdC68 6x10^11 VP + pDNA 5 mg + Treme 40 mg + PF-06801591 130 mg | Change From Baseline in T Cell Response to Prostate Specific Antigen (PSA) in Part A | Cycle 1 Day 1 Compared With Cycle 1 Day 71 | NA SFC/10^6 PBMCS | — |
Secondary
Change From Baseline in T Cell Response to Prostate Specific Membrane Antigen (PSMA) in Part A
T cell response to PSMA was determined by assaying PBMC samples for cellular immune responses against PSMA antigens and was determined as the frequency of IFN-γ SFC/million PBMCs. Change from baseline at Cycle 1 Day 71 and at Cycle 2 Day 99 are presented here.
Time frame: At screening; Cycle 1: at Day 1, Day 15, Day 29, Day 43, Day 71; Cycle 2: at Day 1, Day 29, and Day 99; at the EOT visit, and 2, 4 and 6 months after EOT.
Population: All enrolled participants in Part A who received at least one dose of all assigned regimen components administered on Cycle 1 Day 1 of treatment and must have at least 1 valid and determinate assay result related to the proposed analysis. Number of Participants Analyzed = number of participants evaluable for this OM; Number Analyzed = number of participants evaluable for this OM at the time point specified.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort All mCRPC Patients | Change From Baseline in T Cell Response to Prostate Specific Membrane Antigen (PSMA) in Part A | Cycle 2 Day 1 Compared With Cycle 2 Day 99 | NA SFC/10^6 PBMCS | — |
| Cohort All mCRPC Patients | Change From Baseline in T Cell Response to Prostate Specific Membrane Antigen (PSMA) in Part A | Cycle 1 Day 1 Compared With Cycle 1 Day 71 | 5.50 SFC/10^6 PBMCS | Standard Deviation 9.526 |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Change From Baseline in T Cell Response to Prostate Specific Membrane Antigen (PSMA) in Part A | Cycle 2 Day 1 Compared With Cycle 2 Day 99 | 36.00 SFC/10^6 PBMCS | Standard Deviation 62.354 |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Change From Baseline in T Cell Response to Prostate Specific Membrane Antigen (PSMA) in Part A | Cycle 1 Day 1 Compared With Cycle 1 Day 71 | 28.00 SFC/10^6 PBMCS | Standard Deviation 48.497 |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Change From Baseline in T Cell Response to Prostate Specific Membrane Antigen (PSMA) in Part A | Cycle 2 Day 1 Compared With Cycle 2 Day 99 | NA SFC/10^6 PBMCS | — |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Change From Baseline in T Cell Response to Prostate Specific Membrane Antigen (PSMA) in Part A | Cycle 1 Day 1 Compared With Cycle 1 Day 71 | 4.30 SFC/10^6 PBMCS | Standard Deviation 12.736 |
| Cohort 7A and 3B Combined | Change From Baseline in T Cell Response to Prostate Specific Membrane Antigen (PSMA) in Part A | Cycle 1 Day 1 Compared With Cycle 1 Day 71 | NA SFC/10^6 PBMCS | — |
| Cohort 7A: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 300 mg | Change From Baseline in T Cell Response to Prostate Specific Membrane Antigen (PSMA) in Part A | Cycle 1 Day 1 Compared With Cycle 1 Day 71 | NA SFC/10^6 PBMCS | — |
| Cohort 9A: AdC68 6x10^11 VP + pDNA 5 mg + Treme 40 mg + PF-06801591 130 mg | Change From Baseline in T Cell Response to Prostate Specific Membrane Antigen (PSMA) in Part A | Cycle 1 Day 1 Compared With Cycle 1 Day 71 | NA SFC/10^6 PBMCS | — |
Secondary
Change From Baseline in T Cell Response to Prostate Stem Cell Antigen (PSCA) in Part A
T cell response to PSCA was determined by assaying PBMC samples for cellular immune responses against PSCA antigens and was determined as the frequency of IFN-γ SFC/million PBMCs. Change from baseline at Cycle 1 Day 71 and at Cycle 2 Day 99 are presented here.
Time frame: At screening; Cycle 1: at Day 1, Day 15, Day 29, Day 43, Day 71; Cycle 2: at Day 1, Day 29, and Day 99; at the EOT visit, and 2, 4 and 6 months after EOT.
Population: All enrolled participants in Part A who received at least one dose of all assigned regimen components administered on Cycle 1 Day 1 of treatment and must have at least 1 valid and determinate assay result related to the proposed analysis. Number of Participants Analyzed = number of participants evaluable for this OM; Number Analyzed = number of participants evaluable for this OM at the time point specified.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort All mCRPC Patients | Change From Baseline in T Cell Response to Prostate Stem Cell Antigen (PSCA) in Part A | Cycle 2 Day 1 Compared With Cycle 2 Day 99 | NA SFC/10^6 PBMCS | — |
| Cohort All mCRPC Patients | Change From Baseline in T Cell Response to Prostate Stem Cell Antigen (PSCA) in Part A | Cycle 1 Day 1 Compared With Cycle 1 Day 71 | NA SFC/10^6 PBMCS | — |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Change From Baseline in T Cell Response to Prostate Stem Cell Antigen (PSCA) in Part A | Cycle 2 Day 1 Compared With Cycle 2 Day 99 | NA SFC/10^6 PBMCS | — |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Change From Baseline in T Cell Response to Prostate Stem Cell Antigen (PSCA) in Part A | Cycle 1 Day 1 Compared With Cycle 1 Day 71 | NA SFC/10^6 PBMCS | — |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Change From Baseline in T Cell Response to Prostate Stem Cell Antigen (PSCA) in Part A | Cycle 2 Day 1 Compared With Cycle 2 Day 99 | NA SFC/10^6 PBMCS | — |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Change From Baseline in T Cell Response to Prostate Stem Cell Antigen (PSCA) in Part A | Cycle 1 Day 1 Compared With Cycle 1 Day 71 | 1.70 SFC/10^6 PBMCS | Standard Deviation 3.801 |
| Cohort 7A and 3B Combined | Change From Baseline in T Cell Response to Prostate Stem Cell Antigen (PSCA) in Part A | Cycle 1 Day 1 Compared With Cycle 1 Day 71 | NA SFC/10^6 PBMCS | — |
| Cohort 7A: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 300 mg | Change From Baseline in T Cell Response to Prostate Stem Cell Antigen (PSCA) in Part A | Cycle 1 Day 1 Compared With Cycle 1 Day 71 | NA SFC/10^6 PBMCS | — |
| Cohort 9A: AdC68 6x10^11 VP + pDNA 5 mg + Treme 40 mg + PF-06801591 130 mg | Change From Baseline in T Cell Response to Prostate Stem Cell Antigen (PSCA) in Part A | Cycle 1 Day 1 Compared With Cycle 1 Day 71 | NA SFC/10^6 PBMCS | — |
Secondary
Change in PSADT at Post-Treatment Visit From Baseline in Part B
PSADT was defined as the natural log of 2 divided by the slope of the linear regression line of the natural log of PSA against time in month. PSADT at the post-treatment visit was calculated from C1D1 and all post-treatment PSA values.
Time frame: At screening; Cycle 1 and 2: at Day 1, Day 29, Day 57, and Day 85; at the EOT visit, and 1, 2, 4 and 6 months after EOT.
Population: All enrolled participants in Part B who received at least one dose of all assigned regimen components administered on Cycle 1 Day 1 of treatment and must have at least 1 valid and determinate assay result related to the proposed analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort All mCRPC Patients | Change in PSADT at Post-Treatment Visit From Baseline in Part B | 4.800 Months |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Change in PSADT at Post-Treatment Visit From Baseline in Part B | 4.243 Months |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Change in PSADT at Post-Treatment Visit From Baseline in Part B | 8.078 Months |
Secondary
Change in PSA Slope at Post-Treatment Visit From Baseline in Part B
PSA slope was defined as the slope of the linear regression line of natural log of PSA against time in month. PSA slope at the post-treatment visit was calculated from C1D1 and all post-treatment PSA values.
Time frame: At screening; Cycle 1 and 2: at Day 1, Day 29, Day 57, and Day 85; at the EOT visit, and 1, 2, 4 and 6 months after EOT.
Population: All enrolled participants in Part B who received at least one dose of all assigned regimen components administered on Cycle 1 Day 1 of treatment and must have at least 1 valid and determinate assay result related to the proposed analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort All mCRPC Patients | Change in PSA Slope at Post-Treatment Visit From Baseline in Part B | -0.084 Ratio |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Change in PSA Slope at Post-Treatment Visit From Baseline in Part B | -0.067 Ratio |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Change in PSA Slope at Post-Treatment Visit From Baseline in Part B | 0.076 Ratio |
Secondary
Change in PSA Velocity at Post-Treatment Visit From Baseline in Part B
PSA velocity was defined as the slope of the linear regression line of PSA against time in month. PSA velocity at the post-treatment visit was calculated from C1D1 and all post-treatment PSA values.
Time frame: At screening; Cycle 1 and 2: at Day 1, Day 29, Day 57, and Day 85; at the EOT visit, and 1, 2, 4 and 6 months after EOT.
Population: All enrolled participants in Part B who received at least one dose of all assigned regimen components administered on Cycle 1 Day 1 of treatment and must have at least 1 valid and determinate assay result related to the proposed analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort All mCRPC Patients | Change in PSA Velocity at Post-Treatment Visit From Baseline in Part B | -0.008 ng/ml/month |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Change in PSA Velocity at Post-Treatment Visit From Baseline in Part B | 8.641 ng/ml/month |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Change in PSA Velocity at Post-Treatment Visit From Baseline in Part B | 0.185 ng/ml/month |
Secondary
Cmax of PF-06801591 in Part A
Cmax was defined as the maximum observed plasma concentration. Blood samples (approximately 5 mL) to provide serum for the analysis of PF-06801591 concentrations were collected.
Time frame: Cycle 1: at Day 1 pre-dose, any time between 48 to 120 hr, approximately 168 hr, 336 hr, and 504 hr, at pre-dose on Day 29, Day 57, and Day 85; Cycle 2: at pre-dose on Day 1 and Day 29; at EOT visit, and 2, 4 and 6 months after EOT.
Population: All enrolled participants treated in Part A who had sufficient information to estimate at least 1 of the PK parameters of interest and who had no major protocol deviations influencing the PK assessment. Participants in Part 1 Cohort 6A, 7A, and 9A were treated with PF-06801591, thus included in this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort All mCRPC Patients | Cmax of PF-06801591 in Part A | 8507 ng/mL | Geometric Coefficient of Variation 48 |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Cmax of PF-06801591 in Part A | 19960 ng/mL | Geometric Coefficient of Variation 40 |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Cmax of PF-06801591 in Part A | 8899 ng/mL | Geometric Coefficient of Variation 41 |
Secondary
Ctrough of PF-06801591
Pre-dose PF-06801591 concentration on Cycle 2 Day 1 is presented here as Ctrough. Blood samples (approximately 3 mL whole blood) to provide at least 1 mL of serum for measurement of PF-06801591 PK analysis were collected.
Time frame: Pre-dose on Cycle 2 Day 1
Population: PK parameter analysis population: all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest and who had no major protocol deviations influencing the PK assessment. Participants in Cohort 6A, 7A, 9A, 3B, and 5B were treated with PF-06801591, thus included in this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort All mCRPC Patients | Ctrough of PF-06801591 | NA ng/mL | — |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Ctrough of PF-06801591 | 6873 ng/mL | Standard Deviation 9097.8 |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Ctrough of PF-06801591 | NA ng/mL | — |
| Cohort 7A and 3B Combined | Ctrough of PF-06801591 | 20880 ng/mL | Standard Deviation 12114 |
| Cohort 7A: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 300 mg | Ctrough of PF-06801591 | 3472 ng/mL | Standard Deviation 5085.7 |
Secondary
Duration of PSA-50 Response in Part B
Duration of PSA-50 response was defined as the period from the first measurement when PSA-50 response was achieved to the measurement when PSA-50 response no longer held.
Time frame: Days 1, 29, 57 of Cycle 1 and Cycle 2.
Population: All enrolled participants in Part B who received at least one dose of all assigned regimen components administered on Cycle 1 Day 1 of treatment and must have at least 1 valid and determinate assay result related to the proposed analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort All mCRPC Patients | Duration of PSA-50 Response in Part B | 6.9 Months |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Duration of PSA-50 Response in Part B | 5.6 Months |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Duration of PSA-50 Response in Part B | 4.1 Months |
Secondary
Duration of Response (DOR) by RECIST v1.1 in Cohort 7A and 3B Combined and All mCRPC Patients
DOR was defined as the time from first documentation of confirmed CR or PR to date of first documentation of progressive disease (PD) or death due to any cause according to RECIST v1.1. Per RECIST v1.1: CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm) and no new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all measurable target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease and no new lesions. PD was defined as \>=20% increase in the sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm. Unequivocal progression of pre existing lesions for non-target disease.
Time frame: Baseline up to 6 months after EOT (52 months in maximum)
Population: All enrolled participants in Cohort 1A, 2A, 3A, 6A, 7A, 9A, and 3B who received at least one dose of all assigned regimen components administered on Cycle 1 Day 1 of treatment and must have at least 1 valid and determinate assay result related to the proposed analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort All mCRPC Patients | Duration of Response (DOR) by RECIST v1.1 in Cohort 7A and 3B Combined and All mCRPC Patients | 169 Days |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Duration of Response (DOR) by RECIST v1.1 in Cohort 7A and 3B Combined and All mCRPC Patients | 169 Days |
Secondary
Immune-Related Confirmed DOR by irRECIST v1.1 in Cohort 7A and 3B Combined and All mCRPC Patients
Immune-related confirmed DOR was defined as the time from first documentation of confirmed irCR or confirmed irPR to date of first documentation of immune related progressive disease (irPD) or death due to any cause according to irRECIST. Per irRECIST v1.1: irCR was defined as complete disappearance of all lesions and no new lesions. All measurable lymph nodes also must have a reduction in short axis to \<10 mm. irPR was defined as sum of the diameters (longest for non nodal lesions, shortest for nodal lesions) of target and new measurable lesions must decrease \>=30%. irPD was defined as sum of the diameters of target and new measurable lesions must increase \>=20%, confirmed by a repeat, consecutive observation at least 4 weeks from the date first documented.
Time frame: Baseline up to 6 months after EOT (52 months in maximum)
Population: All enrolled participants in Cohort 1A, 2A, 3A, 6A, 7A, 9A, and 3B who received at least one dose of all assigned regimen components administered on Cycle 1 Day 1 of treatment and must have at least 1 valid and determinate assay result related to the proposed analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort All mCRPC Patients | Immune-Related Confirmed DOR by irRECIST v1.1 in Cohort 7A and 3B Combined and All mCRPC Patients | 169 Days |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Immune-Related Confirmed DOR by irRECIST v1.1 in Cohort 7A and 3B Combined and All mCRPC Patients | 169 Days |
Secondary
Immune-Related Confirmed ORR by Immune Related Response Evaluation Criteria in Solid Tumors Version 1.1 (irRECIST v1.1) in Cohort 7A and 3B Combined and All mCRPC Patients
Immune-related confirmed ORR was defined as the percentage of participants with objective response based assessment of confirmed immune related complete response (irCR) or confirmed immune related partial response (irPR) according to irRECIST v1.1. Per irRECIST v1.1: irCR was defined as complete disappearance of all lesions and no new lesions. All measurable lymph nodes also must have a reduction in short axis to \<10 mm. irPR was defined as sum of the diameters (longest for non nodal lesions, shortest for nodal lesions) of target and new measurable lesions must decrease \>=30%.
Time frame: Baseline up to 6 months after EOT (52 months in maximum)
Population: All enrolled participants in Cohort 1A, 2A, 3A, 6A, 7A, 9A, and 3B who received at least one dose of all assigned regimen components administered on Cycle 1 Day 1 of treatment and must have at least 1 valid and determinate assay result related to the proposed analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort All mCRPC Patients | Immune-Related Confirmed ORR by Immune Related Response Evaluation Criteria in Solid Tumors Version 1.1 (irRECIST v1.1) in Cohort 7A and 3B Combined and All mCRPC Patients | 9.4 Percentage of participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Immune-Related Confirmed ORR by Immune Related Response Evaluation Criteria in Solid Tumors Version 1.1 (irRECIST v1.1) in Cohort 7A and 3B Combined and All mCRPC Patients | 5.6 Percentage of participants |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Tremelimumab in Part A
Cmax was defined as the maximum observed plasma concentration. Blood samples (approximately 3 mL whole blood) to provide at least 1 mL of serum for measurement of tremelimumab PK analysis were collected.
Time frame: Cycle 1: at Day 1 pre-dose, any time between 48 to 120 hr, approximately 168 hr, 336 hr, and 504 hr, at pre-dose on Day 29, Day 57, and Day 85; Cycle 2: at pre-dose on Day 1 and Day 29; at EOT visit, and 2, 4 and 6 months after EOT.
Population: All enrolled participants treated in Part A who had sufficient information to estimate at least 1 of the PK parameters of interest and who had no major protocol deviations influencing the PK assessment. Participants in Part 1 Cohort 3A, 6A, 7A, and 9A were treated with tremelimumab, thus included in this outcome measure. Summary statistics for Cohort 6A, 7A, and 9A are not presented since no participants had reportable parameter values.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort All mCRPC Patients | Maximum Observed Plasma Concentration (Cmax) of Tremelimumab in Part A | 4360 ng/mL | Geometric Coefficient of Variation 31 |
Secondary
Number of Participants Achieving Central PSA Response >= 50% Decline From Baseline (PSA-50) in Part B
PSA-50 response rate was defined as the proportion of patients whose on-study PSA declined from baseline by at least 50% at two consecutive measurements at least 3 weeks apart, prior to other systematic anti-cancer therapy.
Time frame: At screening; Cycle 1 and 2: at Day 1, Day 29, Day 57, and Day 85; at the EOT visit, and 1, 2, 4 and 6 months after EOT.
Population: All enrolled participants in Part B who received at least one dose of all assigned regimen components administered on Cycle 1 Day 1 of treatment and must have at least 1 valid and determinate assay result related to the proposed analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort All mCRPC Patients | Number of Participants Achieving Central PSA Response >= 50% Decline From Baseline (PSA-50) in Part B | 5 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants Achieving Central PSA Response >= 50% Decline From Baseline (PSA-50) in Part B | 1 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants Achieving Central PSA Response >= 50% Decline From Baseline (PSA-50) in Part B | 3 Participants |
Secondary
Number of Participants With ADA Against PF-06801591
Participants were considered ADA-positive if sample titer (log10) \>=99; Participants were considered ADA-negative if sample titer (log10) \<99. Blood samples (approximately 5 mL) to provide at least 1 mL of serum for detection of ADA against PF-06801591 were collected from participants enrolled in Cohorts 6A to 9A and Cohorts 3B and 5B.
Time frame: Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to PF-06801591 dosing.
Population: All enrolled participants who received at least one dose of all assigned regimen components administered on Cycle 1 Day 1 of treatment and must have at least 1 valid and determinate assay result related to the proposed analysis. For this outcome measure, participants are grouped by disease type and PF-06801591 dose as follows: All mCRPC Patients, All BCR Patients, Cohort 7A and 3B Combined (PF-06801591 300 mg), and Cohort 6A, 9A, and 5B Combined (PF-06801591 130 mg).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort All mCRPC Patients | Number of Participants With ADA Against PF-06801591 | 5 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With ADA Against PF-06801591 | 8 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With ADA Against PF-06801591 | 3 Participants |
| Cohort 7A and 3B Combined | Number of Participants With ADA Against PF-06801591 | 10 Participants |
Secondary
Number of Participants With Anti-Drug Antibody (ADA) Against Tremelimumab
Blood samples (approximately 5 mL) to provide at least 1 mL of serum to detect ADA were collected from participants enrolled in to Cohorts 3A to 9A and Cohorts 1B to 5B. Participants were considered ADA-positive if sample titer (log10) \>=1.48; participants were considered ADA-negative if sample titer (log10) \<1.48.
Time frame: Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to tremelimumab dosing.
Population: All enrolled participants who received at least one dose of all assigned regimen components administered on Cycle 1 Day 1 of treatment and must have at least 1 valid and determinate assay result related to the proposed analysis. For this outcome measure, participants are grouped by disease type and tremelimumab dose, as follows: All mCRPC Patients, All BCR Patients, Cohort 9A (tremelimumab 40 mg), and Cohort 3A, 6A, 7A, 1B, 3B, and 5B Combined (tremelimumab 80 mg).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort All mCRPC Patients | Number of Participants With Anti-Drug Antibody (ADA) Against Tremelimumab | 6 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Anti-Drug Antibody (ADA) Against Tremelimumab | 11 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Anti-Drug Antibody (ADA) Against Tremelimumab | 1 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Anti-Drug Antibody (ADA) Against Tremelimumab | 16 Participants |
Secondary
Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4)
Laboratory abnormalities were graded per NCI CTCAE version 4.03 (Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated) and those with at least 1 participant are presented here. Chemistry parameters included aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, sodium, potassium, magnesium, chloride, total calcium, total bilirubin, blood urea nitrogen (or urea), creatinine, uric acid, glucose, albumin, phosphorous or phosphate, lactate dehydrogenase, lipase, bicarbonate or carbon dioxide, total protein, TSH (if abnormal, reflex free T4 and free T3).
Time frame: Baseline up to 6 months after EOT (52 months in maximum)
Population: Safety analysis set: all enrolled participants who received at least one dose of one of the components of the regimen. For this outcome measure, participants are grouped by disease type and treatment, as follows: Cohort All mCRPC Patients (all mCRPC participants), Cohort 1B (BCR with 1 ICI), Cohort 5B (BCR with 2 ICIs), and Cohort 7A and 3B Combined (mCRPC at RP2D dose).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort All mCRPC Patients | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Alanine aminotransferase | 1 Participants |
| Cohort All mCRPC Patients | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Creatinine | 1 Participants |
| Cohort All mCRPC Patients | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypocalcemia | 0 Participants |
| Cohort All mCRPC Patients | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypoalbuminemia | 0 Participants |
| Cohort All mCRPC Patients | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypernatremia | 0 Participants |
| Cohort All mCRPC Patients | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypercalcemia | 0 Participants |
| Cohort All mCRPC Patients | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypoglycemia | 0 Participants |
| Cohort All mCRPC Patients | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Lipase | 9 Participants |
| Cohort All mCRPC Patients | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hyponatremia | 0 Participants |
| Cohort All mCRPC Patients | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hyperglycemia | 4 Participants |
| Cohort All mCRPC Patients | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Alkaline phosphatase | 0 Participants |
| Cohort All mCRPC Patients | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Amylase | 2 Participants |
| Cohort All mCRPC Patients | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypophosphatemia | 2 Participants |
| Cohort All mCRPC Patients | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hyperkalemia | 1 Participants |
| Cohort All mCRPC Patients | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Bilirubin (total) | 0 Participants |
| Cohort All mCRPC Patients | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Aspartate aminotransferase | 1 Participants |
| Cohort All mCRPC Patients | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypomagnesemia | 0 Participants |
| Cohort All mCRPC Patients | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypermagnesemia | 7 Participants |
| Cohort All mCRPC Patients | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypokalemia | 3 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypermagnesemia | 8 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypokalemia | 0 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypernatremia | 0 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypophosphatemia | 5 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypoalbuminemia | 0 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypoglycemia | 0 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypocalcemia | 0 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Aspartate aminotransferase | 0 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Bilirubin (total) | 1 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Alkaline phosphatase | 0 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Creatinine | 0 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Alanine aminotransferase | 0 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hyponatremia | 1 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypercalcemia | 0 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hyperglycemia | 0 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypomagnesemia | 0 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hyperkalemia | 0 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Amylase | 0 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Lipase | 3 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hyponatremia | 2 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Alanine aminotransferase | 1 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Alkaline phosphatase | 0 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Amylase | 0 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Aspartate aminotransferase | 1 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Bilirubin (total) | 0 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Creatinine | 0 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypercalcemia | 0 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hyperglycemia | 0 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hyperkalemia | 0 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypermagnesemia | 6 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypernatremia | 0 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypoalbuminemia | 0 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypocalcemia | 0 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypoglycemia | 0 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypokalemia | 0 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypomagnesemia | 0 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypophosphatemia | 4 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Lipase | 2 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypermagnesemia | 1 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Alkaline phosphatase | 0 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypokalemia | 2 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hyperkalemia | 0 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hyperglycemia | 2 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Alanine aminotransferase | 0 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypomagnesemia | 0 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypercalcemia | 0 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Creatinine | 0 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Bilirubin (total) | 0 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hyponatremia | 0 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Aspartate aminotransferase | 0 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Amylase | 0 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Lipase | 6 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypocalcemia | 0 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypoalbuminemia | 0 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypophosphatemia | 1 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypoglycemia | 0 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypernatremia | 0 Participants |
Secondary
Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4)
Laboratory abnormalities were graded per NCI CTCAE version 4.03 (Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated) and those with at least 1 participant are presented here. Hematology parameters included hemoglobin, platelets, white blood cell count, neutrophils, eosinophils, monocytes, basophils and lymphocytes.
Time frame: Baseline up to 6 months after EOT (52 months in maximum)
Population: Safety analysis set: all enrolled participants who received at least one dose of one of the components of the regimen. For this outcome measure, participants are grouped by disease type and treatment, as follows: Cohort All mCRPC Patients (all mCRPC participants), Cohort 1B (BCR with 1 ICI), Cohort 5B (BCR with 2 ICIs), and Cohort 7A and 3B Combined (mCRPC at RP2D dose).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort All mCRPC Patients | Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4) | Anemia | 2 Participants |
| Cohort All mCRPC Patients | Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4) | Platelets | 0 Participants |
| Cohort All mCRPC Patients | Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4) | Neutrophils (absolute) | 1 Participants |
| Cohort All mCRPC Patients | Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4) | Hemoglobin increased | 0 Participants |
| Cohort All mCRPC Patients | Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4) | White blood cells | 1 Participants |
| Cohort All mCRPC Patients | Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4) | Lymphocyte count increased | 0 Participants |
| Cohort All mCRPC Patients | Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4) | Lymphopenia | 7 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4) | Platelets | 0 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4) | Lymphopenia | 2 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4) | Lymphocyte count increased | 0 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4) | Neutrophils (absolute) | 0 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4) | White blood cells | 0 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4) | Hemoglobin increased | 0 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4) | Anemia | 0 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4) | Lymphopenia | 2 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4) | Anemia | 0 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4) | Hemoglobin increased | 0 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4) | Lymphocyte count increased | 0 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4) | Neutrophils (absolute) | 0 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4) | Platelets | 0 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4) | White blood cells | 0 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4) | Lymphocyte count increased | 0 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4) | White blood cells | 1 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4) | Platelets | 0 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4) | Hemoglobin increased | 0 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4) | Anemia | 2 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4) | Neutrophils (absolute) | 1 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4) | Lymphopenia | 4 Participants |
Secondary
Number of Participants With Laboratory Abnormalities in Urinalysis (Grade 3 or 4)
Laboratory abnormalities were graded per NCI CTCAE version 4.03 (Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated) and those with at least 1 participant are presented here. Urine parameters included urine protein and urine blood.
Time frame: Baseline up to 6 months after EOT (52 months in maximum)
Population: Safety analysis set: all enrolled participants who received at least one dose of one of the components of the regimen. For this outcome measure, participants are grouped by disease type and treatment, as follows: Cohort All mCRPC Patients (all mCRPC participants), Cohort 1B (BCR with 1 ICI), Cohort 5B (BCR with 2 ICIs), and Cohort 7A and 3B Combined (mCRPC at RP2D dose).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort All mCRPC Patients | Number of Participants With Laboratory Abnormalities in Urinalysis (Grade 3 or 4) | 0 Participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Number of Participants With Laboratory Abnormalities in Urinalysis (Grade 3 or 4) | 0 Participants |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Number of Participants With Laboratory Abnormalities in Urinalysis (Grade 3 or 4) | 0 Participants |
| Cohort 7A and 3B Combined | Number of Participants With Laboratory Abnormalities in Urinalysis (Grade 3 or 4) | 0 Participants |
Secondary
Number of Participants With NAb Against PF-06801591
Only those samples tested positive for ADA were to be further tested for Nab. Blood samples (approximately 5 mL) to provide at least 1 mL of serum for detection of NAb against PF-06801591 were collected from participants enrolled in Cohorts 6A to 9A and Cohorts 3B and 5B. Nab against PF-06801591 was not examined due to business reason.
Time frame: Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to PF-06801591 dosing.
Population: All enrolled participants who received at least one dose of all assigned regimen components administered on Cycle 1 Day 1 of treatment and must have at least 1 valid and determinate assay result related to the proposed analysis. For this outcome measure, participants are grouped by disease type and PF-06801591 dose, as follows: All mCRPC Patients, All BCR Patients, Cohort 7A and 3B Combined (PF-06801591 300 mg), and Cohort 6A, 9A, and 5B Combined (PF-06801591 130 mg).
Secondary
Number of Participants With Neutralizing Antibody (NAb) Against Tremelimumab
Only those samples tested positive for ADA were to be further tested for Nab. Blood samples (approximately 5 mL) to provide at least 1 mL of serum to detect NAb were collected from participants enrolled in to Cohorts 3A to 9A and Cohorts 1B to 5B. Nab against tremelimumab was not examined due to business reason.
Time frame: Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to tremelimumab dosing.
Population: All enrolled participants who received at least one dose of all assigned regimen components administered on Cycle 1 Day 1 of treatment and must have at least 1 valid and determinate assay result related to the proposed analysis. For this outcome measure, participants are grouped by disease type and tremelimumab dose as follows: All mCRPC Patients, All BCR Patients, Cohort 9A (tremelimumab 40 mg), and Cohort 3A, 6A, 7A, 1B, 3B, and 5B Combined (tremelimumab 80 mg).
Secondary
Number of Patients With Bone Progression Per Prostrate Cancer Working Group 3 (PCWG3) Criteria in Cohort 7A and 3B Combined
Number of participants with bone progression per Prostate Cancer Clinical Trials Working Group 3 (PCWG3). Per PCWG3, progressing disease on bone scan was considered when at least two new lesions relative to the first post treatment scan was confirmed on a subsequent scan (6 or more weeks later).
Time frame: Baseline up to 6 months after EOT (52 months in maximum)
Population: All enrolled participants in Cohort 7A and 3B who received at least one dose of all assigned regimen components administered on Cycle 1 Day 1 of treatment and must have at least 1 valid and determinate assay result related to the proposed analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort All mCRPC Patients | Number of Patients With Bone Progression Per Prostrate Cancer Working Group 3 (PCWG3) Criteria in Cohort 7A and 3B Combined | 2 Participants |
Secondary
Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Cohort 7A and 3B Combined and All mCRPC Patients
ORR was defined as the percentage of participants with best overall response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST v1.1. Per RECIST v1.1: CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm) and no new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease and no new lesions.
Time frame: Baseline up to 6 months after EOT (52 months in maximum)
Population: All enrolled participants in Cohort 1A, 2A, 3A, 6A, 7A, 9A, and 3B who received at least one dose of all assigned regimen components administered on Cycle 1 Day 1 of treatment and must have at least 1 valid and determinate assay result related to the proposed analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort All mCRPC Patients | Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Cohort 7A and 3B Combined and All mCRPC Patients | 9.4 Percentage of participants |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Cohort 7A and 3B Combined and All mCRPC Patients | 5.6 Percentage of participants |
Secondary
Radiographic Progression Free Survival (rPFS) Per RECIST v1.1 in Cohort 7A and 3B Combined , All mCRPC Patients, Cohort 1B, and Cohort 5B
Radiographic Progression Free Survival (rPFS) per RECIST v1.1. rPFS was defined as the time from first dose of study treatment to date of first documentation of radiographic PD or death due to any cause, whichever occurs first. Per RECIST v1.1, PD was defined as \>=20% increase in the sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm. Unequivocal progression of pre existing lesions for non-target disease. The Kaplan Meier estimate of median rPFS was presented here.
Time frame: Baseline up to 6 months after EOT (52 months in maximum)
Population: All enrolled participants who received at least one dose of all assigned regimen components administered on Cycle 1 Day 1 of treatment and must have at least 1 valid and determinate assay result related to the proposed analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort All mCRPC Patients | Radiographic Progression Free Survival (rPFS) Per RECIST v1.1 in Cohort 7A and 3B Combined , All mCRPC Patients, Cohort 1B, and Cohort 5B | 5.6 Months |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Radiographic Progression Free Survival (rPFS) Per RECIST v1.1 in Cohort 7A and 3B Combined , All mCRPC Patients, Cohort 1B, and Cohort 5B | 5.6 Months |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Radiographic Progression Free Survival (rPFS) Per RECIST v1.1 in Cohort 7A and 3B Combined , All mCRPC Patients, Cohort 1B, and Cohort 5B | NA Months |
| Cohort 7A and 3B Combined | Radiographic Progression Free Survival (rPFS) Per RECIST v1.1 in Cohort 7A and 3B Combined , All mCRPC Patients, Cohort 1B, and Cohort 5B | NA Months |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tremelimumab in Part A
Tmax was defined as the time to reach maximum observed plasma concentration. Blood samples (approximately 3 mL whole blood) to provide at least 1 mL of serum for measurement of tremelimumab PK analysis were collected.
Time frame: Cycle 1: at Day 1 pre-dose, any time between 48 to 120 hr, approximately 168 hr, 336 hr, and 504 hr, at pre-dose on Day 29, Day 57, and Day 85; Cycle 2: at pre-dose on Day 1 and Day 29; at EOT visit, and 2, 4 and 6 months after EOT.
Population: All enrolled participants treated in Part A who had sufficient information to estimate at least 1 of the PK parameters of interest and who had no major protocol deviations influencing the PK assessment. Participants in Part 1 Cohort 3, 6, 7, and 9 were treated with tremelimumab, thus included in this outcome measure. Summary statistics for Cohort 6A, 7A, and 9A are not presented since no participants had reportable parameter values.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort All mCRPC Patients | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tremelimumab in Part A | 307 Hour |
Secondary
Titer of Treatment-Induced ADA Against PF-06801591
Treatment-induced ADA was defined as baseline titer missing or negative and participant had \>=1 post-treatment positive titer. Blood samples (approximately 5 mL) to provide at least 1 mL of serum for detection of ADA against PF-06801591 were collected from participants enrolled in Cohorts 6A to 9A and Cohorts 3B and 5B.
Time frame: Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to PF-06801591 dosing.
Population: All enrolled participants who received at least one dose of all assigned regimen components administered on Cycle 1 Day 1 of treatment and must have at least 1 valid and determinate assay result related to the proposed analysis. For this outcome measure, participants are grouped by disease type and PF-06801591 dose, as follows: All mCRPC Patients, All BCR Patients, Cohort 7A and 3B Combined (PF-06801591 300 mg), and Cohort 6A, 9A, and 5B Combined (PF-06801591 130 mg).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort All mCRPC Patients | Titer of Treatment-Induced ADA Against PF-06801591 | 880 1/dilution |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Titer of Treatment-Induced ADA Against PF-06801591 | 2010 1/dilution |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Titer of Treatment-Induced ADA Against PF-06801591 | 790 1/dilution |
| Cohort 7A and 3B Combined | Titer of Treatment-Induced ADA Against PF-06801591 | 2010 1/dilution |
Secondary
Titer of Treatment-Induced ADA Against Tremelimumab
Treatment-induced ADA was defined as baseline titer missing or negative and participant had \>=1 post-treatment positive titer. Blood samples (approximately 5 mL) to provide at least 1 mL of serum to detect ADA were collected from participants enrolled in to Cohorts 3A to 9A and Cohorts 1B to 5B.
Time frame: Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to tremelimumab dosing.
Population: All enrolled participants who received at least one dose of all assigned regimen components administered on Cycle 1 Day 1 of treatment and must have at least 1 valid and determinate assay result related to the proposed analysis. For this outcome measure, participants are grouped by disease type and tremelimumab dose as follows: All mCRPC Patients, All BCR Patients, Cohort 9A (tremelimumab 40 mg), and Cohort 3A, 6A, 7A, 1B, 3B, and 5B Combined (tremelimumab 80 mg).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort All mCRPC Patients | Titer of Treatment-Induced ADA Against Tremelimumab | 2.81 1/dilution |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Titer of Treatment-Induced ADA Against Tremelimumab | 2.34 1/dilution |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Titer of Treatment-Induced ADA Against Tremelimumab | 2.68 1/dilution |
| Cohort 7A and 3B Combined | Titer of Treatment-Induced ADA Against Tremelimumab | 2.70 1/dilution |
Secondary
Titer of Treatment-Induced NAb Against PF-06801591
Only those samples tested positive for ADA were to be further tested for Nab. Blood samples (approximately 5 mL) to provide at least 1 mL of serum for detection of NAb against PF-06801591 were collected from participants enrolled in Cohorts 6A to 9A and Cohorts 3B and 5B. Nab against PF-06801591 was not examined due to business reason.
Time frame: Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to PF-06801591 dosing.
Population: All enrolled participants who received at least one dose of all assigned regimen components administered on Cycle 1 Day 1 of treatment and must have at least 1 valid and determinate assay result related to the proposed analysis. For this outcome measure, participants are grouped by disease type and PF-06801591 dose, as follows: All mCRPC Patients, All BCR Patients, Cohort 7A and 3B Combined (PF-06801591 300 mg), and Cohort 6A, 9A, and 5B Combined (PF-06801591 130 mg).
Secondary
Titer of Treatment-Induced NAb Against Tremelimumab
Only those samples tested positive for ADA were to be further tested for Nab. Blood samples (approximately 5 mL) to provide at least 1 mL of serum to detect NAb were collected from participants enrolled in to Cohorts 3A to 9A and Cohorts 1B to 5B. Nab against tremelimumab was not examined due to business reason.
Time frame: Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to tremelimumab dosing.
Population: All enrolled participants who received at least one dose of all assigned regimen components administered on Cycle 1 Day 1 of treatment and must have at least 1 valid and determinate assay result related to the proposed analysis. For this outcome measure, participants are grouped by disease type and tremelimumab dose as follows: All mCRPC Patients, All BCR Patients, Cohort 9A (tremelimumab 40 mg), and Cohort 3A, 6A, 7A, 1B, 3B, and 5B Combined (tremelimumab 80 mg).
Secondary
Tmax of PF-06801591 in Part A
Tmax was defined as the time at which Cmax occurred. Blood samples (approximately 5 mL) to provide serum for the analysis of PF- 06801591 concentrations were collected.
Time frame: Cycle 1: at Day 1 pre-dose, any time between 48 to 120 hr, approximately 168 hr, 336 hr, and 504 hr, at pre-dose on Day 29, Day 57, and Day 85; Cycle 2: at pre-dose on Day 1 and Day 29; at EOT visit, and 2, 4 and 6 months after EOT.
Population: All enrolled participants treated in Part A who had sufficient information to estimate at least 1 of the PK parameters of interest and who had no major protocol deviations influencing the PK assessment. Participants in Part 1 Cohort 6A, 7A, and 9A were treated with PF-06801591, thus included in this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort All mCRPC Patients | Tmax of PF-06801591 in Part A | 164 Hour |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Tmax of PF-06801591 in Part A | 188 Hour |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Tmax of PF-06801591 in Part A | 166 Hour |
Secondary
Trough Concentrations (Ctrough) After Multiple Dosing of Tremelimumab
Pre-dose tremelimumab concentration on Cycle 2 Day 1 is presented here as Ctrough. Blood samples (approximately 3 mL whole blood) to provide at least 1 mL of serum for measurement of tremelimumab PK analysis were collected. Summary statistics of Ctrough were not calculated if number of observations above lower lit of quantification (NALQ)=0 or \<=3 participants had non-missing data.
Time frame: Pre-dose on Cycle 2 Day 1
Population: PK parameter analysis population: all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest and who had no major protocol deviations influencing the PK assessment. Participants in Cohort 3A, 6A, 7A, 9A, 1B, 3B, and 5B were treated with tremelimumab, thus included in this outcome measure. Number of Participants Analyzed = Number of participants who had non-missing data and were evaluable for this OM.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort All mCRPC Patients | Trough Concentrations (Ctrough) After Multiple Dosing of Tremelimumab | NA ng/mL | — |
| Cohort 1B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg | Trough Concentrations (Ctrough) After Multiple Dosing of Tremelimumab | NA ng/mL | — |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Trough Concentrations (Ctrough) After Multiple Dosing of Tremelimumab | 5130 ng/mL | Standard Deviation 1844.4 |
| Cohort 7A and 3B Combined | Trough Concentrations (Ctrough) After Multiple Dosing of Tremelimumab | NA ng/mL | — |
| Cohort 7A: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 300 mg | Trough Concentrations (Ctrough) After Multiple Dosing of Tremelimumab | 4750 ng/mL | Standard Deviation 2573.5 |
| Cohort 9A: AdC68 6x10^11 VP + pDNA 5 mg + Treme 40 mg + PF-06801591 130 mg | Trough Concentrations (Ctrough) After Multiple Dosing of Tremelimumab | 4849 ng/mL | Standard Deviation 2726.7 |
| Cohort 5B: AdC68 6x10^11 VP + pDNA 5 mg + Treme 80 mg + PF-06801591 130 mg | Trough Concentrations (Ctrough) After Multiple Dosing of Tremelimumab | 5320 ng/mL | Standard Deviation 1114.5 |