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

Phase 1
Recruiting
Conditions
Peripheral T Cell Lymphoma
Diffuse Large B-cell Lymphoma
Classical Hodgkin Lymphoma
Head and Neck Squamous Cell Carcinoma
Melanoma
Non-Small Cell Lung Cancer
Interventions
Registration Number
NCT06870487
Lead Sponsor
Pfizer
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
220
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
PF-08046032 Monotherapy Dose EscalationPF-08046032PF-08046032 will be given as an intravenous (IV) infusion.
PF-08046032 + Sasanlimab Combination Safety EvaluationPF-08046032PF-08046032 will be given as an intravenous (IV) infusion and sasanlimab will be administered as a subcutaneous injection.
PF-08046032 + Sasanlimab Combination Safety EvaluationSasanlimabPF-08046032 will be given as an intravenous (IV) infusion and sasanlimab will be administered as a subcutaneous injection.
PF-08046032 + Sasanlimab Combination Expansion CohortPF-08046032PF-08046032 will be given as an intravenous (IV) infusion and sasanlimab will be administered as a subcutaneous injection.
PF-08046032 + Sasanlimab Combination Expansion CohortSasanlimabPF-08046032 will be given as an intravenous (IV) infusion and sasanlimab will be administered as a subcutaneous injection.
Primary Outcome Measures
NameTimeMethod
Part A and Part B: Number of participants with dose limiting toxicities (DLTs) in dose escalationDay of first dose (Day 1) through the end of DLT Observation period (up to 28 days)

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

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

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

All Parts: Frequency of dose modifications due to AEsFrom 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

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

All Parts: Number of participants with clinically significant lab abnormalitiesFrom 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

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

Secondary Outcome Measures
NameTimeMethod
Objective Response Rate (ORR) in Participants with Solid TumorsResponse assessments at baseline and every 8 to 12 weeks through time of disease progression, death, unacceptable toxicity, or through study completion (Approximately 3 Years)

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

Duration of Response (DoR) in Participants with Solid TumorsTime from first documented objective response to the date of first documented radiographic progression or death (Approximately 3 Years)

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

Progression-free survival (PFS) in Participants with Solid TumorsTime from first dose (Day 1) to the date of first documented radiographic progression or death (Approximately 3 Years)

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

Objective Response Rate (ORR) in participants with lymphomas based on Lugano CriteriaResponse assessments at baseline and every 8 to 12 weeks through time of disease progression, death, unacceptable toxicity, or through study completion (Approximately 3 Years)

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

Progression-free survival (PFS) in participants with lymphomas based on Lugano CriteriaTime from first dose (Day 1) to the date of first documented radiographic progression or death (Approximately 3 Years)

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

Duration of Response (DoR) in participants with lymphomas based on Lugano CriteriaTime from first documented objective response to the date of first documented radiographic progression or death (Approximately 3 Years)

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

Complete Response Rate (CRR) in participants with lymphomasResponse assessments at baseline and every 8 to 12 weeks through time of disease progression, death, unacceptable toxicity, or through study completion (Approximately 3 Years)

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

Duration of Complete Response (DCR) in participants with lymphomasTime from first documented CR to the date of the first radiographic progression or death (Approximately 3 Years)

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

Part C only: Overall survival (OS)Baseline through date of death or study completion, whichever occurs first (up to approximately 3 Years)

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

Part A2 only: Change from baseline of the number of CD25+ cells in tumor in response to PF-08046032 treatmentBaseline through about 7 weeks after first dose

Change is evaluated from paired biopsies

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

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

PK: Maximum Observed Serum Concentration (Cmax)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)

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)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)

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)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)

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)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)

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)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)

Immunogenicity of PF-08046032 and in combination with sasanlimab

Trial Locations

Locations (3)

Fred Hutchinson Cancer Center.

🇺🇸

Seattle, Washington, United States

University of Washington Medical Center- Montlake

🇺🇸

Seattle, Washington, United States

NEXT Oncology

🇺🇸

San Antonio, Texas, United States

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