A Study to Learn About PF-07921585 Alone or With Other Anti-cancer Medicines in People With Cancer
A PHASE 1, OPEN-LABEL, DOSE ESCALATION AND DOSE EXPANSION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND ANTI-TUMOR ACTIVITY OF PF-07921585 AS A SINGLE AGENT AND IN COMBINATION THERAPY IN PARTICIPANTS 18 YEARS OF AGE AND OLDER WITH ADVANCED SOLID TUMORS
Key
1. Participants aged ≥18 years or older at the time of informed consent.
2. Tumor types and prior treatment requirements: Participants entering Parts 2 and 3 must have at least 1 measurable lesion.
Part 1 and Part 2:
Eligible advanced/metastatic tumor types include NSCLC, urothelial carcinoma (UC), renal cell carcinoma (RCC), melanoma, head and neck squamous cell carcinoma (HNSCC), and microsatellite stable colorectal cancer (MSS-CRC). Participants must have demonstrated radiographic progression on standard treatment(s) for their cancer
Part 3:
* Cohort 1: Participants with metastatic melanoma with resistance to checkpoint inhibitor therapy and BRAF/MEKi.
* Cohort 2: Participants with metastatic MSS-CRC.
* Cohort 3: Participants with previously untreated metastatic NSCLC.
3. ECOG PS 0 or 1.
Key Exclusion Criteria:
1. Participants with any other active malignancy within 3 years prior to enrollment.
2. Known or suspected hypersensitivity to, or severe allergic history of, human albumin or anti-PD-(L)1 therapy.
3. History of Grade ≥3 immune-related AE (irAE) or unresolved irAEs prior to first dose of study intervention. Exception: vitiligo and endocrinopathy that is controlled with hormonal therapy.
4. History of venous thromboembolic event \<12 weeks prior to starting study treatment.
5. Active or history of clinically significant gastrointestinal (GI) disease.
6. Active or history of interstitial lung disease or Grade ≥2 pneumonitis.
7. Active or history of clinically significant autoimmune disease.
8. Active bleeding disorder.
9. Participants who have undergone treatment with any investigational IL-12 agent.
10. Active, uncontrolled infections
Key Exclusion Criteria: 1. Participants with any other active malignancy within 3 years prior to enrollment. 2. Known or suspected hypersensitivity to, or severe allergic history of, human albumin or anti-PD-(L)1 therapy. 3. History of Grade ≥3 immune-related AE (irAE) or unresolved irAEs prior to first dose of study intervention. Exception: vitiligo and endocrinopathy that is controlled with hormonal therapy. 4. History of venous thromboembolic event \<12 weeks prior to starting study treatment. 5. Active or history of clinically significant gastrointestinal (GI) disease. 6. Active or history of interstitial lung disease or Grade ≥2 pneumonitis. 7. Active or history of clinically significant autoimmune disease. 8. Active bleeding disorder. 9. Participants who have undergone treatment with any investigational IL-12 agent. 10. Active, uncontrolled infections
Participant Group/Arm
EXPERIMENTAL: Part 1
Dose escalation monotherapy
Intervention/Treatment
BIOLOGICAL: PF-07921585
IL-12 mutein, solution, administered once every 3 weeks intravenously or subcutaneouslyParticipant Group/Arm
EXPERIMENTAL: Part 2
Dose escalation (combination therapy)
Intervention/Treatment
BIOLOGICAL: PF-07921585
IL-12 mutein, solution, administered once every 3 weeks intravenously or subcutaneouslyBIOLOGICAL: Sasanlimab
Anti-PD1 antibody solution, administered once every 3 weeks subcutaneouslyParticipant Group/Arm
EXPERIMENTAL: Part 3
Dose optimization/ expansion (combination therapy)
Intervention/Treatment
BIOLOGICAL: PF-07921585
IL-12 mutein, solution, administered once every 3 weeks intravenously or subcutaneouslyBIOLOGICAL: Sasanlimab
Anti-PD1 antibody solution, administered once every 3 weeks subcutaneouslyOutcome Measure
Number of Participants With Dose-Limiting Toxicity (DLT) (Parts 1 and 2)
Measure Description
Specific adverse events occurring during the first 21 days of study medication and considered at least possibly-related to study medication
Time Frame
Baseline up to Cycle 2 (each cycle is 21 days)
Outcome Measure
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs (Parts 1 and 2)
Measure Description
AEs are any untoward medical occurrence in a participant who received study drug. Serious adverse event (SAE) are AEs resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 or 90 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Time Frame
Baseline up to 28 days after the last dose of PF-07921585 or after 90 days after the last dose of sasanlimab
Outcome Measure
Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities (Parts 1 and 2)
Measure Description
Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.
Time Frame
Baseline up to 28 days after the last dose of PF-07921585 or after 90 days after the last dose of sasanlimab
Outcome Measure
Objective Response Rate - Percentage of Participants With Objective Response (Part 3)
Measure Description
Percentage of participants with objective response based assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors 1. 1 (RECIST 1.1). 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 \=30% decrease under baseline of the sum of diameters of all target lesions. The short aixs 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. No new lesions.
Time Frame
Date of first dose up to 2 years
Outcome Measure
Number of Participants with Treatment emergent Adverse Events (AEs) and Serious AEs (Part 3)
Measure Description
AEs are any untoward medical occurrence in a participant who received study drug. Serious adverse event (SAE) are AEs resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 or 90 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Time Frame
Baseline up to 28 days after the last dose of PF-07921585 and 90 days after the last dose of sasanlimab
Outcome Measure
Objective Response Rate-Percentage of Participants with objective response (Parts 1 and 2)
Measure Description
Percentage of participants with objective response based assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors 1. 1 (RECIST 1.1). 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 \=30% decrease under baseline of the sum of diameters of all target lesions. The short aixs 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. No new lesions.
Time Frame
Date of first dose up to 2 years
Outcome Measure
Duration of response (DOR)-Parts 1-3
Measure Description
Time in weeks or months from the first documentation of objective tumor response that is subsequently confirmed to objective tumor progression or death due to any cause.
Time Frame
Date of first dose up to 2 years
Outcome Measure
Disease control rate (DCR)-Parts 1-3
Measure Description
DCR is defined as the percent of participants with a confirmed complete response (CR), partial response (PR) or stable disease (SD) according to RECIST 1.1, at 6 weeks.
Time Frame
Date of first dose up to 2 years
Outcome Measure
Progression Free survival (PFS)-Parts 1-3
Measure Description
Time in weeks or months from first dose to first documentation of objective tumor progression per RECIST 1.1 or death due to any cause.
Time Frame
Date of first dose until disease progression or death, up to a maximum of 4 years
Outcome Measure
Overall Survival (OS)-Part 3
Measure Description
Time in weeks or months from the start of study treatment to date of death due to any cause.
Time Frame
Date of first dose until death, up to a maximum of 4 years
Outcome Measure
Pharmacokinetic Parameters: Time to Reach Maximum Observed Plasma Concentration (Tmax)-PF-07921585
Measure Description
Single dose PK of PF-07921585 as monotherapy (Part 1) and in combination with sansalimab (Parts 2-3) will be calculated. Additional parameters may be calculated if data permits
Time Frame
At specific timepoints from Cycle 1 day 1 up to 2 years
Outcome Measure
Pharmacokinetic Parameters: Time to Reach Maximum Observed Plasma Concentration (Tmax ss)-PF-07921585
Measure Description
Multiple dose PK of PF-07921585 as monotherapy (Part 1) and in combination with sasanlimab (Parts 2-3) will be calculated. Additional parameters may be calculated if data permits
Time Frame
At specific timepoints from Cycle 1 day 1 up to 2 years
Outcome Measure
Pharmacokinetic Parameters: Area under the curve (AUCt)-PF-07921585
Measure Description
Single dose PK of PF-07921585 as monotherapy (Part 1) and in combination with sasanlimab (Parts 2-3) will be calculated. Additional parameters may be calculated if data permits
Time Frame
At specific timepoints from Cycle 1 day 1 up to 2 years
Outcome Measure
Pharmacokinetic Parameters: Area under the curve (AUCt ss)-PF-07921585
Measure Description
Multiple dose PK of PF-07921585 as monotherapy (Part 1) and in combination with sasanlimab (Parts 2-3) will be calculated. Additional parameters may be calculated if data permits
Time Frame
At specific timepoints from Cycle 1 day 1 up to 2 years
Outcome Measure
Pharmacokinetic Parameters: Cmax (maximum drug concentration in the body)-PF-07921585
Measure Description
Single dose PK of PF-07921585 as monotherapy will be calculated. Additional parameters may be calculated if data permits
Time Frame
At specific timepoints from Cycle 1 day 1 up to 2 years
Outcome Measure
Pharmacokinetic Parameters: Cmax ss (maximum drug concentration in the body)-PF-07921585
Measure Description
Multiple dose PK of PF-07921585 as monotherapy (Part 1) and in combination with sasanlimab (Parts 2-3) will be calculated. Additional parameters may be calculated if data permits
Time Frame
At specific timepoints from Cycle 1 day 1 up to 2 years
Outcome Measure
Percentage of Participants With Positive PF-07921585 Anti-Drug Antibody (ADA)
Measure Description
Percentage of ADA positive participants by dose level (Parts 1-3)
Time Frame
At specific timepoints from Cycle 1 day 1 up to 2 years
Outcome Measure
Percentage of Participants With Positive PF-07921585 neutralizing antibodies (Nab)
Measure Description
Percentage of Nab positive participants by dose level (Parts 1-3)
Time Frame
At specific timepoints from Cycle 1 Day 1 up to 2 years
Outcome Measure
Incidence and titer of PF-07921585 ADA and Nab
Measure Description
Parts 1-3
Time Frame
At specific timepoints from Cycle 1 Day 1 up to 2 years
Outcome Measure
Pharmacokinetic Parameters: C through-Sasanlimab
Measure Description
PK of sasanlimab (Parts 2 and 3)
Time Frame
At specific timepoints, predose, from Cycle 1 day 1 up to 2 years
Outcome Measure
Percentage of Participants With Positive sasanlimab Anti-Drug Antibody (ADA)
Measure Description
Percentage of ADA positive participants by dose level (Parts 2-3)
Time Frame
At specific timepoints from Cycle 1 day 1 up to 2 years
Outcome Measure
Percentage of Participants With Positive sasanlimab neutralizing antibodies (Nab)
Measure Description
Percentage of Nab positive participants by dose level (Parts 2-3)
Time Frame
At specific timepoints from Cycle 1 Day 1 up to 2 years
Outcome Measure
Incidence and titer of sasanlimab ADA and Nab
Measure Description
Parts 2-3
Time Frame
At specific timepoints from Cycle 1 Day 1 up to 2 years
Pfizer
