The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.
PF-07921585 is an investigational compound. Its safety and efficacy have not been established.
Active enrolling
United States
for more information at clinicaltrials.gov
EXPERIMENTAL: Part 1
Dose escalation monotherapy
BIOLOGICAL: PF-07921585
IL-12 mutein, solution, administered once every 3 weeks intravenously or subcutaneously
EXPERIMENTAL: Part 2
Dose escalation (combination therapy)
BIOLOGICAL: PF-07921585
IL-12 mutein, solution, administered once every 3 weeks intravenously or subcutaneously
BIOLOGICAL: Sasanlimab
Anti-PD1 antibody solution, administered once every 3 weeks subcutaneously
EXPERIMENTAL: Part 3
Dose optimization/ expansion (combination therapy)
BIOLOGICAL: PF-07921585
IL-12 mutein, solution, administered once every 3 weeks intravenously or subcutaneously
BIOLOGICAL: Sasanlimab
Anti-PD1 antibody solution, administered once every 3 weeks subcutaneously
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
Number of Participants With Dose-Limiting Toxicity (DLT) (Parts 1 and 2)
Specific adverse events occurring during the first 21 days of study medication and considered at least possibly-related to study medication
Baseline up to Cycle 2 (each cycle is 21 days)
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs (Parts 1 and 2)
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.
Baseline up to 28 days after the last dose of PF-07921585 or after 90 days after the last dose of sasanlimab
Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities (Parts 1 and 2)
Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.
Baseline up to 28 days after the last dose of PF-07921585 or after 90 days after the last dose of sasanlimab
Objective Response Rate - Percentage of Participants With Objective Response (Part 3)
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.
Date of first dose up to 2 years
Number of Participants with Treatment emergent Adverse Events (AEs) and Serious AEs (Part 3)
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.
Baseline up to 28 days after the last dose of PF-07921585 and 90 days after the last dose of sasanlimab
Objective Response Rate-Percentage of Participants with objective response (Parts 1 and 2)
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.
Date of first dose up to 2 years
Duration of response (DOR)-Parts 1-3
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.
Date of first dose up to 2 years
Disease control rate (DCR)-Parts 1-3
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.
Date of first dose up to 2 years
Progression Free survival (PFS)-Parts 1-3
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.
Date of first dose until disease progression or death, up to a maximum of 4 years
Overall Survival (OS)-Part 3
Time in weeks or months from the start of study treatment to date of death due to any cause.
Date of first dose until death, up to a maximum of 4 years
Pharmacokinetic Parameters: Time to Reach Maximum Observed Plasma Concentration (Tmax)-PF-07921585
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
At specific timepoints from Cycle 1 day 1 up to 2 years
Pharmacokinetic Parameters: Time to Reach Maximum Observed Plasma Concentration (Tmax ss)-PF-07921585
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
At specific timepoints from Cycle 1 day 1 up to 2 years
Pharmacokinetic Parameters: Area under the curve (AUCt)-PF-07921585
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
At specific timepoints from Cycle 1 day 1 up to 2 years
Pharmacokinetic Parameters: Area under the curve (AUCt ss)-PF-07921585
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
At specific timepoints from Cycle 1 day 1 up to 2 years
Pharmacokinetic Parameters: Cmax (maximum drug concentration in the body)-PF-07921585
Single dose PK of PF-07921585 as monotherapy will be calculated. Additional parameters may be calculated if data permits
At specific timepoints from Cycle 1 day 1 up to 2 years
Pharmacokinetic Parameters: Cmax ss (maximum drug concentration in the body)-PF-07921585
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
At specific timepoints from Cycle 1 day 1 up to 2 years
Percentage of Participants With Positive PF-07921585 Anti-Drug Antibody (ADA)
Percentage of ADA positive participants by dose level (Parts 1-3)
At specific timepoints from Cycle 1 day 1 up to 2 years
Percentage of Participants With Positive PF-07921585 neutralizing antibodies (Nab)
Percentage of Nab positive participants by dose level (Parts 1-3)
At specific timepoints from Cycle 1 Day 1 up to 2 years
Incidence and titer of PF-07921585 ADA and Nab
Parts 1-3
At specific timepoints from Cycle 1 Day 1 up to 2 years
Pharmacokinetic Parameters: C through-Sasanlimab
PK of sasanlimab (Parts 2 and 3)
At specific timepoints, predose, from Cycle 1 day 1 up to 2 years
Percentage of Participants With Positive sasanlimab Anti-Drug Antibody (ADA)
Percentage of ADA positive participants by dose level (Parts 2-3)
At specific timepoints from Cycle 1 day 1 up to 2 years
Percentage of Participants With Positive sasanlimab neutralizing antibodies (Nab)
Percentage of Nab positive participants by dose level (Parts 2-3)
At specific timepoints from Cycle 1 Day 1 up to 2 years
Incidence and titer of sasanlimab ADA and Nab
Parts 2-3
At specific timepoints from Cycle 1 Day 1 up to 2 years
190
Sponsor: Pfizer
Collaborator: None
For more information, call or email the Pfizer Clinical Trial Contact Center:
When calling, please reference this study number:
NCT# stands for National Clinical Trial number. This is a unique identification code given to each clinical trial registered on ClinicalTrials.gov. The format is "NCT" followed by an 8-digit number (for example, NCT00000419). Also called the ClinicalTrials.gov identifier.
NCT06580938
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