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

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.

Study Overview

• Status: Terminated
• Conditions: Melanoma; Renal Cell Carcinoma; Head and Neck Cancer; Colorectal Cancer; Non Small Cell Lung Cancer; Bladder Cancer
• Intervention / Treatment: Biological: PF-07921585; Biological: Sasanlimab

Detailed Description

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
• Enrollment (Actual): 4
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group
    • Rogers, Arkansas, United States, 72758
      • Highlands Oncology Group
    • Springdale, Arkansas, United States, 72762
      • Highlands Oncology Group
  • Colorado
    • Denver, Colorado, United States, 80218
      • Sarah Cannon Research Institute at HealthONE
    • Denver, Colorado, United States, 80218
      • Presbyterian/St. Lukes Medical Center
  • Florida
    • Sarasota, Florida, United States, 34232
      • Florida Cancer Specialists Sarasota Drug Development Unit
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • START Midwest
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • SCRI Oncology Partners
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute- Pharmacy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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; Other Names: PF-06801591
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; Other Names: PF-06801591

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 <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.	Date of first dose up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 <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.	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

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2024
• Primary Completion (Actual): July 14, 2025
• Study Completion (Actual): July 14, 2025

Study Registration Dates

• First Submitted: August 5, 2024
• First Submitted That Met QC Criteria: August 28, 2024
• First Posted (Actual): August 30, 2024

Study Record Updates

• Last Update Posted (Actual): March 23, 2026
• Last Update Submitted That Met QC Criteria: March 19, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: lung cancer; anti-PD1 antibody; Sasanlimab; Interleukin-12 mutein
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Intestinal Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Lung Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Respiratory Tract Neoplasms; Thoracic Neoplasms; Colonic Diseases; Skin Diseases; Urologic Neoplasms; Carcinoma; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Kidney Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Urinary Bladder Diseases; Skin and Connective Tissue Diseases; Lung Neoplasms; Colorectal Neoplasms; Carcinoma, Renal Cell; Carcinoma, Non-Small-Cell Lung; Head and Neck Neoplasms; Melanoma; Urinary Bladder Neoplasms
• Other Study ID Numbers: C5461001; NCT06580938 (Registry Identifier: ClinicalTrials.gov)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No