A Study to Learn About PF-07921585 Alone or With Other Anti-cancer Medicines in People With Cancer

Phase 1TerminatedNCT06580938

Pfizer4 enrolled

Overview

The purpose of this study is to learn about the safety and effects of the study medicine (called PF-07921585) in people with cancer that has advanced or spread to other parts of the body. This study is seeking participants who have any of the following cancer types: * non-small cell lung cancer * colorectal cancer * bladder cancer * melanoma (a type of skin cancer) * kidney cancer * head and neck cancer Participants will receive the study medicine PF-07921585 alone or in combination with another study medicine called sasanlimab at the study clinic. PF-07921585 will be given as an infusion into a vein or as shots under the skin, once every 3 weeks. Sasanlimab will be given as shots under the skin, also once every 3 weeks. The experiences of participants receiving the study medicine will be studied to help see if the study medicine is safe and effective. Participants may receive study medicine for up to 2 years, depending on how the cancer responds to the study treatment. Participants may continue receiving study medicine after 2 years if there are any benefits from the study treatment. Participants will attend visits once every 3 weeks with the first 9 weeks having more frequent visits, to check the safety of the study treatment.

The study contains 3 parts: Part 1: dose escalation of PF-07921585 as single agent to determine the monotherapy recommended dose for further study. Part 2: dose escalation of PF-07921585 in combination with the anti-PD 1 inhibitor sasanlimab and potentially other anti-cancer agents, in order to determine the recommended dose for expansion of the combination. Part 3: dose optimization/ expansion will evaluate PF-07921585 in combination with sasanlimab, and potentially other anti-cancer agents. After identification of the recommended dose for expansion in Part 2, participants with select solid tumors will be enrolled into 3-4 cohorts as follows: * Cohort 1: Melanoma * Cohort 2: Microsatellite stable (MSS) metastatic colorectal cancer * Cohort 3: Non-small cell lung cancer (NSCLC) * Cohort 4: Solid tumor, tumor types and clinical setting to be determined based on emerging data.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Interventions

PF-07921585BIOLOGICAL

IL-12 mutein, solution, administered once every 3 weeks intravenously or subcutaneously

SasanlimabBIOLOGICAL

Anti-PD1 antibody solution, administered once every 3 weeks subcutaneously

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: 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

Locations (8)

Highlands Oncology Group

Fayetteville, Arkansas, United States

Highlands Oncology Group

Rogers, Arkansas, United States

Highlands Oncology Group

Springdale, Arkansas, United States

Presbyterian/St. Lukes Medical Center

Denver, Colorado, United States

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, United States

Florida Cancer Specialists Sarasota Drug Development Unit

Sarasota, Florida, United States

START Midwest

Grand Rapids, Michigan, United States

SCRI Oncology Partners

Nashville, Tennessee, United States

Outcomes

Primary Outcomes

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

Time frame: 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.

Time frame: 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.

Time frame: 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 \<10 mm). No new lesions. PR was defined as \>=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

Secondary Outcomes

Number of Participants with Treatment emergent Adverse Events (AEs) and Serious AEs (Part 3)

Time frame: 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)

Time frame: 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.

Time frame: 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.

Time frame: Date of first dose up to 2 years

Progression Free survival (PFS)-Parts 1-3

Data from ClinicalTrials.gov

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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

Overall Survival (OS)-Part 3

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

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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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)

Time frame: 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)

Time frame: At specific timepoints from Cycle 1 Day 1 up to 2 years

Incidence and titer of PF-07921585 ADA and Nab

Parts 1-3

Time frame: At specific timepoints from Cycle 1 Day 1 up to 2 years

Pharmacokinetic Parameters: C through-Sasanlimab

PK of sasanlimab (Parts 2 and 3)

Time frame: 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)

Time frame: 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)

Time frame: At specific timepoints from Cycle 1 Day 1 up to 2 years

Incidence and titer of sasanlimab ADA and Nab

Parts 2-3

Time frame: At specific timepoints from Cycle 1 Day 1 up to 2 years

A Study to Learn About PF-07921585 Alone or With Other Anti-cancer Medicines in People With Cancer

Overview

Conditions

Interventions

Eligibility

Locations (8)

Outcomes

Primary Outcomes

Secondary Outcomes