A Study of PF-07820435 as a Single Agent and in Combination in Participants With Advanced Solid Tumors

A PHASE 1 DOSE ESCALATION AND EXPANSION STUDY TO EVALUATE SAFETY, TOLERABILITY, PHARMACOKINETIC, PHARMACODYNAMIC, AND ANTITUMOR ACTIVITY OF PF-07820435 AS MONOTHERAPY AND IN COMBINATION IN PARTICIPANTS WITH ADVANCED SOLID TUMORS

This study aims to evaluate the safety, and early signals of anti-tumor activity of PF-07820435 when administered alone (Part 1A) or in combination with sasanlimab (Part 1B; Part 2) in patients with selected advanced or metastatic solid tumors. Part 1 will be dose-finding and Part 2 of the study will further evaluate PF-07820435 at the recommended dose for combination expansion in patients with selected advanced solid tumors.

Study Overview

• Status: Recruiting
• Conditions: Melanoma; Neoplasms; Renal Cell Carcinoma; Non-small-cell Lung Cancer; Squamous Cell Carcinoma of the Head and Neck; Urothelial Carcinoma; Colorectal Carcinoma; Ovarian Carcinoma
• Intervention / Treatment: Drug: PF-07820435; Biological: Sasanlimab

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Pfizer CT.gov Call Center; Phone Number: 1-800-718-1021; Email: ClinicalTrials.gov_Inquiries@pfizer.com

Study Locations

• Japan
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • Not yet recruiting
      • National Cancer Center Hospital East
  • Tokyo
    • Koto, Tokyo, Japan, 135-8550
      • Not yet recruiting
      • The Cancer Institute Hospital of JFCR
• Puerto Rico
  • Rio Piedras, Puerto Rico, 00935
    • Recruiting
    • Pan American Center for Oncology Trials, LLC
  • Rio Piedras, Puerto Rico, 00935
    • Recruiting
    • Hospital Oncologico Dr. Isaac Gonzalez-Martinez
• United States
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Not yet recruiting
      • START Midwest
    • Grand Rapids, Michigan, United States, 49503
      • Not yet recruiting
      • Corewell Health (reference non-engagement letter)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histological or cytological diagnosis of advanced, unresectable, and/or metastatic or relapsed/refractory solid tumor
• Part 1A: Participants with solid tumors where anti-PD-(L)1 is an established treatment. Participants must have progressed on or following prior anti-PD-(L)1 therapy if approved, available, tolerable, and eligible
• Part 1B: Participants either meeting Part 1A criterion, or participants with "cold" solid tumors where anti-PD-(L)1 therapy is not an established treatment
• Part 2: Participants with NSCLC (Arm A) must have received platinum-based chemotherapy and anti-PD-(L)1 or have intolerability to or refusal of standard therapies. NSCLC participants with known activating mutation(s) must also have received prior approved and available targeted therapy(ies) for the associated mutation(s) or have intolerability or documented refusal of these therapies. Participants with UC (Arm B) must have received prior platinum-based chemotherapy, anti-PD-(L)1 therapy, or enfortumab vedotin, or have documented intolerability or refusal of the standard therapy(ies). Additional cohort indication(s) or dose regimens may be added and defined based on emerging data
• At least 1 measurable lesion based on RECIST 1.1 that has not been previously irradiated (Part 1 exceptions permitted after review and approval)
• Able to provide pre-treatment (and optional on-treatment) tumor tissue

Exclusion Criteria:

• Active or history of clinically significant gastrointestinal disease and other conditions that are unresolved or pose a risk to study treatment or procedures
• Active or history of pneumonitis/interstitial lung disease, pulmonary fibrosis requiring treatment with systemic steroid therapy
• Active or history of clinically significant autoimmune disease or other medical condition that required chronic systemic immunosuppressive therapy within recent 2 years
• History of severe immune-mediated adverse event or cytokine release syndrome that was considered related to prior immune modulatory therapy that required immunosuppressive therapy

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

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Monotherapy dose escalation (Part 1A); Participants will receive PF-07820435 orally at the prescribed dose and frequency in 28-day cycles	Drug: PF-07820435; immune agonist
Experimental: Combination dose escalation (Part 1B); Participants will receive PF-07820435 orally at the prescribed dose and frequency, in combination with sasanlimab (subcutaneous injection) at a fixed dose once every 4 weeks in 28-day cycles	Drug: PF-07820435; immune agonist; Biological: Sasanlimab; A monoclonal antibody that blocks the interaction between PD-1 and PD-L1/L2
Experimental: Expansion (Part 2) - Tumor specific Arm A; Participants will receive PF-07820435 orally at the prescribed dose and frequency in combination with sasanlimab SC once every 4 weeks in 28-day cycles	Drug: PF-07820435; immune agonist; Biological: Sasanlimab; A monoclonal antibody that blocks the interaction between PD-1 and PD-L1/L2
Experimental: Expansion (Part 2) - Tumor specific Arm B; Participants will receive PF-07820435 orally at the prescribed dose and frequency in combination with sasanlimab SC once every 4 weeks in 28-day cycles	Drug: PF-07820435; immune agonist; Biological: Sasanlimab; A monoclonal antibody that blocks the interaction between PD-1 and PD-L1/L2
Experimental: Expansion (Part 2) - Arm C; Participants will receive PF-07820435 orally at the prescribed dose and frequency in 28-day cycles	Drug: PF-07820435; immune agonist

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with dose limiting toxicities (DLTs) in dose escalation (Part 1A and Part 1B)	DLT rate estimated based on data from DLT-evaluable participants during the DLT evaluation period	Baseline through 28 days after first dose
Number of patients with adverse events (AEs)	Characterized by type, frequency, severity (CTCAE v5; CRS by ASTCT), timing, seriousness, and relationship to study drug(s)	Baseline through up to 2 years
Number of patients with clinically significant lab abnormalities	Characterized by type, frequency, severity (CTCAE v5), and timing	Baseline through up to 2 years
Objective response rate (ORR) in Part 2 Expansion	Tumor response as assessed using RECIST 1.1	Baseline through 2 years or disease progression

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR) in dose escalation (Part 1A and Part 1B)	Tumor response as assessed by RECIST 1.1	Baseline through 2 years or disease progression
Duration of tumor response	Tumor response as assessed by RECIST 1.1	Baseline through 2 years or disease progression
Progression free survival (PFS)	Tumor response as assessed by RECIST 1.1	Baseline through 2 years or disease progression
Cmax (maximum concentration) of PF-07820435 and its active metabolite	Single and multiple dose PK parameters of PF-07820435 and its active metabolite	Serial timepoints following the first dose (Day 1), second dose (Day 8), and third dose (Day 15) of the first cycle (each cycle is 28 days); and Day 1 (dosing) of Cycle 2 and Day 1 (dosing) of Cycle 3.
Tmax (time to maximal plasma concentration) of PF-07820435 and its active metabolite	Single and multiple dose PK parameters of PF-07820435 and its active metabolite	Serial timepoints following the first dose (Day 1), second dose (Day 8), and third dose (Day 15) of the first cycle (each cycle is 28 days); and Day 1 (dosing) of Cycle 2 and Day 1 (dosing) of Cycle 3.
AUClast (area under the curve from time 0 to the last measurable timepoint) of PF-07820435 and its active metabolite	Single and multiple dose PK parameters of PF-07820435 and its active metabolite	Serial timepoints following the first dose (Day 1), second dose (Day 8), and third dose (Day 15) of the first cycle (each cycle is 28 days); and Day 1 (dosing) of Cycle 2 and Day 1 (dosing) of Cycle 3.
Cmin (minimum concentration) of PF-07820435 and its active metabolite after multiple dosing only	Multiple dose PK parameters of PF-07820435 and its active metabolite	Serial timepoints following the first dose (Day 1), second dose (Day 8), and third dose (Day 15) of the first cycle (each cycle is 28 days); and Day 1 (dosing) of Cycle 2 and Day 1 (dosing) of Cycle 3.
Change from baseline of immune markers within biopsied tumor tissue	Change in CD8 immune marker will be analyzed	Baseline through about 6 weeks after first dose
Pre-dose trough concentrations of sasanlimab (Part 1B and Part 2)	Single and multiple dose PK parameters of sasanlimab	Day 1 (pre-dose) of each cycle (28 days) for the first 3 cycles, then Day 1 on every 3rd cycle until 2 years or disease progression
Incidence and titers of ADA and NAb against sasanlimab (Part 1B and Part 2)	Immunogenicity assessment	Day 1 (pre-dose) of each cycle (28 days) for the first 3 cycles, then Day 1 on every 3rd cycle until 2 years or disease progression
Cmax of PF-07820435 and its active metabolite under fasted and fed conditions (Part 2 subset) subset of participants in Part 2	The analysis applies to Part 2 Food Effect Subset only	On Day 1 (first dose) and Day 15 (third dose): Pre-dose, 0.5 hour (h), 1h, 2h, 4h, 6h, and 24h post dose.
Tmax of PF-07820435 and its active metabolite under fasted and fed conditions (Part 2 subset) subset of participants in Part 2	The analysis applies to Part 2 Food Effect Subset only	On Day 1 (first dose) and Day 15 (third dose): Pre-dose, 0.5 hour (h), 1h, 2h, 4h, 6h, and 24h post dose.
AUC of PF-07820435 and its active metabolite under fasted and fed conditions (Part 2 subset) subset of participants in Part 2	The analysis applies to Part 2 Food Effect Subset only	On Day 1 (first dose) and Day 15 (third dose): Pre-dose, 0.5 hour (h), 1h, 2h, 4h, 6h, and 24h post dose.

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): February 8, 2024
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): January 31, 2028

Study Registration Dates

• First Submitted: January 23, 2024
• First Submitted That Met QC Criteria: February 26, 2024
• First Posted (Actual): February 29, 2024

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: immunotherapy; solid tumor; Sasanlimab; anti-Programmed death receptor-1 (PD-1)
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Kidney Neoplasms; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Carcinoma, Squamous Cell; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carcinoma, Renal Cell; Carcinoma; Colorectal Neoplasms; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: C5391001

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