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

Phase 1TerminatedNCT06285097

Pfizer9 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Neoplasms Non-small-cell Lung Cancer Melanoma Squamous Cell Carcinoma of the Head and Neck Renal Cell Carcinoma

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (10)

Florida Cancer Specialists Sarasota Drug Development Unit

Sarasota, Florida, United States

Corewell Health (reference non-engagement letter)

Grand Rapids, Michigan, United States

START Midwest

Grand Rapids, Michigan, United States

Sarah Cannon Research Institute - Pharmacy

Nashville, Tennessee, United States

SCRI Oncology Partners

Nashville, Tennessee, United States

Tristar Centennial Medical Center

Nashville, Tennessee, United States

National Cancer Center Hospital East

Kashiwa, Chiba, Japan

The Cancer Institute Hospital of JFCR

Koto, Tokyo, Japan

Hospital Oncologico Dr. Isaac Gonzalez-Martinez

Rio Piedras, Puerto Rico

Pan American Center for Oncology Trials, LLC

Rio Piedras, Puerto Rico

Outcomes

Primary Outcomes

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

Time frame: 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)

Time frame: Baseline through up to 2 years

Number of patients with clinically significant lab abnormalities

Characterized by type, frequency, severity (CTCAE v5), and timing

Time frame: Baseline through up to 2 years

Objective response rate (ORR) in Part 2 Expansion

Tumor response as assessed using RECIST 1.1

Time frame: Baseline through 2 years or disease progression

Secondary Outcomes

Objective response rate (ORR) in dose escalation (Part 1A and Part 1B)

Tumor response as assessed by RECIST 1.1

Time frame: Baseline through 2 years or disease progression

Duration of tumor response

Tumor response as assessed by RECIST 1.1

Time frame: Baseline through 2 years or disease progression

Progression free survival (PFS)

Tumor response as assessed by RECIST 1.1

Time frame: 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

Time frame: 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

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

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

Change from baseline of immune markers within biopsied tumor tissue

Change in CD8 immune marker will be analyzed

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: On Day 1 (first dose) and Day 15 (third dose): Pre-dose, 0.5 hour (h), 1h, 2h, 4h, 6h, and 24h post dose.

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

Overview

Conditions

Interventions

Eligibility

Locations (10)

Outcomes

Primary Outcomes

Secondary Outcomes