Clinical trial NCT06870487: A Study to Learn About the Study Medicine Called PF-08046032 in People With Advanced Cancers.
Official title: An Open-Label Phase 1 Study to Evaluate PF-08046032 as Monotherapy and Part of Combination Therapy in Participants With Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
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
Keywords: Solid tumors
Advanced Malignancies
Malignancies
Lung cancer
Skin cancer
Non-Hodgkin lymphoma
Hodgkin lymphoma
Advanced Cancers
Head and Neck Cancer
Metastatic Cancer
Blood Cancer
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2025-03-11
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Part A and Part B: Number of participants with dose limiting toxicities (DLTs) in dose escalation
timeFrame: Day of first dose (Day 1) through the end of DLT Observation period (up to 28 days)
measure: All Parts: Number of participants with adverse events (AEs)
timeFrame: 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
measure: All Parts: Frequency of dose modifications due to AEs
timeFrame: 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
measure: All Parts: Number of participants with clinically significant lab abnormalities
timeFrame: 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:
measure: Objective Response Rate (ORR) in Participants with Solid Tumors
timeFrame: 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)
measure: Duration of Response (DoR) in Participants with Solid Tumors
timeFrame: Time from first documented objective response to the date of first documented radiographic progression or death (Approximately 3 Years)
measure: Progression-free survival (PFS) in Participants with Solid Tumors
timeFrame: Time from first dose (Day 1) to the date of first documented radiographic progression or death (Approximately 3 Years)
measure: Objective Response Rate (ORR) in participants with lymphomas based on Lugano Criteria
timeFrame: 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)
measure: Progression-free survival (PFS) in participants with lymphomas based on Lugano Criteria
timeFrame: Time from first dose (Day 1) to the date of first documented radiographic progression or death (Approximately 3 Years)
measure: Duration of Response (DoR) in participants with lymphomas based on Lugano Criteria
timeFrame: Time from first documented objective response to the date of first documented radiographic progression or death (Approximately 3 Years)
measure: Complete Response Rate (CRR) in participants with lymphomas
timeFrame: 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)
measure: Duration of Complete Response (DCR) in participants with lymphomas
timeFrame: Time from first documented CR to the date of the first radiographic progression or death (Approximately 3 Years)
measure: Part C only: Overall survival (OS)
timeFrame: Baseline through date of death or study completion, whichever occurs first (up to approximately 3 Years)
measure: Part A2 only: Change from baseline of the number of CD25+ cells in tumor in response to PF-08046032 treatment
timeFrame: Baseline through about 7 weeks after first dose
measure: Pharmacokinetics (PK): Serum Area Under the Curve (AUC) from Time Zero to Last Quantifiable Concentration (AUClast)
timeFrame: 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)
measure: PK: Maximum Observed Serum Concentration (Cmax)
timeFrame: 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)
measure: PK: Half-life (t1/2)
timeFrame: 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)
measure: PK: Minimum observed serum concentration (Ctrough)
timeFrame: 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)
measure: PK: Time to Reach Maximum Observed Serum Concentration (Tmax)
timeFrame: 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)
measure: 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)
timeFrame: 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)
Other outcomes:
Locations:
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center.
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center- Montlake
state: Washington
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
state: Barcelona [barcelona]
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: