A Study to Learn About the Study Medicine Called PF-08046032 in People With Advanced Cancers

Phase 1Active Not RecruitingNCT06870487

Pfizer6 enrolled

Overview

The purpose of this study is to learn about the effects of a new study medicine called PF-08046032, when taken alone and when taken with another medicine called sasanlimab, for the treatment of advanced cancers. The effects are studied in adult participants with certain types of lymphomas or solid tumors that are advanced or metastatic (spread to other parts of the body). The study has three parts: * Part A will test PF-08046032 alone at increasing dose levels in participants with certain lymphomas (cancer that begins in cells of the immune system) and in participants with certain solid tumors whose disease has worsened on or after standard treatments. * Part B will test PF-08046032 (at selected doses) and sasanlimab in participants with certain solid tumors, including those whose disease has worsened on or after standard treatments as well as participants before receiving standard treatments. * Part C will further test the combination of PF-08046032 and sasanlimab in participants with specific types of solid tumors based on the results from Part A and Part B of the study. All participants will receive the study drug PF-08046032. Only participants in Part B and Part C of the study will also receive sasanlimab. PF-08046032 will be given as an intravenous (IV) infusion, which means it will be injected directly into a vein. Sasanlimab will be given as a subcutaneous injection, which means it will be injected under the skin.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Peripheral T Cell Lymphoma

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

INCLUSION CRITERIA: 1. Histological or cytological diagnosis of metastatic or unresectable malignancy: * Part A1: Participants with lymphomas (cHL, PTCL, large B-cell lymphoma) who have progressed on/after standard therapies * Part A2: Participants with solid tumors (NSCLC, HNSCC, melanoma, or other limited tumor types) who have progressed on or following prior immune checkpoint inhibitor if indicated and available * Part B: Participants with solid tumors who have either progressed on/after prior immune checkpoint inhibitor, or who have not received prior immune checkpoint inhibitor therapy * Part C: Participants with selected tumor type who have not received systemic anticancer treatment for the tumor type (including prior immune checkpoint inhibitor 2. Measurable disease as defined by Lugano Classification for lymphomas or RECIST 1.1 for solid tumors 3. Able to provide tumor tissue(s) as defined by the protocol depending on the Part of the study at enrollment 4. ECOG Performance Status score 0 or 1 EXCLUSION CRITERIA: 1. Ongoing peripheral neuropathy 2. History of significant immune-mediated adverse event considered related to prior immune-modulatory therapy 3. Known or suspected active autoimmune disease

Locations (5)

NEXT Oncology

San Antonio, Texas, United States

Fred Hutchinson Cancer Center.

Seattle, Washington, United States

University of Washington Medical Center- Montlake

Seattle, Washington, United States

Hospital Universitari Vall d'Hebron

Barcelona, Barcelona [barcelona], Spain

Hospital Universitario Fundación Jiménez Díaz

Madrid, Spain

Outcomes

Primary Outcomes

Part A and Part B: Number of participants with dose limiting toxicities (DLTs) in dose escalation

DLT (any of the prespecified AEs that are attributable to study treatment(s), excluding toxicities clearly due to underlying disease or extraneous causes) rate estimated based on data from DLT-evaluable participants during the DLT evaluation period

Time frame: Day of first dose (Day 1) through the end of DLT Observation period (up to 28 days)

All Parts: Number of participants with adverse events (AEs)

AEs as characterized by type, frequency, severity (CTCAE v5), seriousness, and relationship to study drug(s)

Time frame: From first dose (Day 1) through up to 30 days after last dose of PF-08046032 or up to 90 days after last dose of sasanlimab

All Parts: Frequency of dose modifications due to AEs

Dose modifications such as dose delay, treatment interruptions, dose reducations, and treatment discontinuations due to AEs

Time frame: From first dose (Day 1) through up to 30 days after last dose of PF-08046032 or up to 90 days after last dose of sasanlimab

All Parts: Number of participants with clinically significant lab abnormalities

Lab abnormalities characterized by type, frequency, and severity (CTCAE v5)

Time frame: From first dose (Day 1) through up to 30 days after last dose of PF-08046032 or up to 90 days after last dose of sasanlimab

Secondary Outcomes

Objective Response Rate (ORR) in Participants with Solid Tumors

Based on investigator assessment, and defined as the proportion of participants who achieved best overall response of CR or PR according to RECIST 1.1

Time frame: Response assessments at baseline and every 8 to 12 weeks through time of disease progression, death, unacceptable toxicity, or through study completion (Approximately 3 Years)

Duration of Response (DoR) in Participants with Solid Tumors

Based on investigator assessment for participants with a confirmed objective response (CR or PR) only.

Time frame: Time from first documented objective response to the date of first documented radiographic progression or death (Approximately 3 Years)

Progression-free survival (PFS) in Participants with Solid Tumors

Based on investigator assessment for tumor response/progression according to RECIST v1.1

Time frame: Time from first dose (Day 1) to the date of first documented radiographic progression or death (Approximately 3 Years)

Objective Response Rate (ORR) in participants with lymphomas based on Lugano Criteria

Based on investigator assessment, and defined as the proportion of participants who achieved best overall response according to Lugano Criteria

Time frame: Response assessments at baseline and every 8 to 12 weeks through time of disease progression, death, unacceptable toxicity, or through study completion (Approximately 3 Years)

Progression-free survival (PFS) in participants with lymphomas based on Lugano Criteria

Based on investigator assessment for tumor response/progression according to Lugano Response Classification Criteria

Time frame: Time from first dose (Day 1) to the date of first documented radiographic progression or death (Approximately 3 Years)

Duration of Response (DoR) in participants with lymphomas based on Lugano Criteria

Based on investigator assessment for participants with a confirmed objective response only.

Time frame: Time from first documented objective response to the date of first documented radiographic progression or death (Approximately 3 Years)

Complete Response Rate (CRR) in participants with lymphomas

Based on investigator assessment, and defined as the proportion of participants who achieved best overall response of Complete Response (CR) according to Lugano Criteria

Time frame: Response assessments at baseline and every 8 to 12 weeks through time of disease progression, death, unacceptable toxicity, or through study completion (Approximately 3 Years)

Duration of Complete Response (DCR) in participants with lymphomas

Based on investigator assessment for participants with lymphoma with a confirmed objective response per Lugano Criteria only.

Time frame: Time from first documented CR to the date of the first radiographic progression or death (Approximately 3 Years)

Part C only: Overall survival (OS)

OS is defined as time from first dose of study treatment to death due to any cause.

Time frame: Baseline through date of death or study completion, whichever occurs first (up to approximately 3 Years)

Part A2 only: Change from baseline of the number of CD25+ cells in tumor in response to PF-08046032 treatment

Change is evaluated from paired biopsies

Time frame: Baseline through about 7 weeks after first dose

Pharmacokinetics (PK): Serum Area Under the Curve (AUC) from Time Zero to Last Quantifiable Concentration (AUClast)

AUClast of PF-08046032 as a monotherapy (Part A) and in combination with sasanlimab (Part B and Part C).

Time frame: Cycle 1 and Cycle 2, and pre-and post-dosing on Day 1 of Cycle 3, 4, 6, 8, and every 4th cycle thereafter; and within approximately 30 days after last dose of study drug (each cycle is 28 days)

PK: Maximum Observed Serum Concentration (Cmax)

Cmax of of PF-08046032 as a monotherapy (Part A) and in combination with sasanlimab (Part B and Part C).

PK: Half-life (t1/2)

Half life of PF-08046032 as a monotherapy (Part A) and in combination with sasanlimab (Part B and Part C)

PK: Minimum observed serum concentration (Ctrough)

Ctrough of PF-08046032 as a monotherapy (Part A) and in combination with sasanlimab (Part B and Part C)

PK: Time to Reach Maximum Observed Serum Concentration (Tmax)

Tmax of PF-08046032 as a monotherapy (Part A) and in combination with sasanlimab (Part B and Part C)

Incidence of Anti-Drug Antibody (ADA): Immunogenicity of PF-08046032 as a single agent (Part A) and in combination with sasanlimab (Part B and Part C)

Immunogenicity of PF-08046032 and in combination with sasanlimab

Time frame: Pre-dose on Day 1 of Cycles 1-4, then cycle 6, 8, and every 4th cycle thereafter, and within approximately 30 days after last dose of study drug (each cycle is 28 days)

A Study to Learn About the Study Medicine Called PF-08046032 in People With Advanced Cancers

Overview

Conditions

Interventions

Eligibility

Locations (5)

Outcomes

Primary Outcomes

Secondary Outcomes