A Clinical Trial of PF-08046037 Alone or With Sasanlimab in Patients With Advanced or Metastatic Malignancies

Phase 1Active Not RecruitingNCT06974734

Pfizer9 enrolled

Overview

The purpose of this study is to learn about the safety and the effects of PF-08046037 alone or with sasanlimab for the treatment of certain advanced or metastatic malignancies. This study is seeking participants who: * have advanced or metastatic non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), melanoma, or pancreatic ductal adenocarcinoma (PDAC); * are able to provide tumor tissue samples; * have measurable disease. All participants will receive while at the clinic PF-08046037 alone as an intravenous (IV) infusion (given directly into a vein) or with sasanlimab as a subcutaneous (SQ) injection (given under the skin) once every 3 weeks. Participants will continue to take the study drug(s) until their cancer is no longer responding or if the patient cannot safely take them. The study team will monitor how each participant is doing with the study treatment during regular visits at the study clinic.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Carcinoma, Non Small Cell Lung Carcinoma, Pancreatic Ductal Malignant Melanoma

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

This study is seeking participants who have the following tumor types and can provide tumor tissue samples as per below. 1. Tumor types * Monotherapy Dose Escalation (Part 1a) and Optimization (Part 2a) cohorts * Advanced or metastatic NSCLC, HNSCC, melanoma, or PDAC * Must have progressive disease following at least 1 prior approved systemic therapy * Monotherapy Dose Expansion (Part 3a) • Advanced or metastatic NSCLC or PDAC * Combination Safety Evaluation (Part 1b) and Dose Optimization (Part 2b) * Advanced or metastatic NSCLC or HNSCC * May be either a) not received prior immunotherapy for the tumor type OR b) relapse/ refractory after prior immunotherapy * Combination Dose Expansion (Part 3b) * Unresectable locally advanced or metastatic HNSCC or NSCLC * Must not have received prior systemic cytotoxic therapy in the locally advanced or metastatic setting (first-line setting) * Must be treatment naïve to any immunotherapy * NSCLC must have PD-L1 expression TPS \>=50% * HNSCC must have PD-L1 expression CPS \>=1 2. Tissue requirement * Part 1 at lower doses: sufficient archival tissue collected within 12 months of enrollment for submission to central laboratory * Part 1 at higher doses: de novo baseline tumor biopsy or archival tissue within 12 months of enrollment * Part 1 backfill: de novo baseline and on-treatment tumor biopsies are required * Part 2 and 3: de novo baseline or archival tissue within 6 months of enrollment * Part 2 and 3: mandatory on-treatment tumor biopsy, if required by sponsor 3. Measurable disease per RECIST v1.1 Participants who meet the following might not be able to participate. 1. History of Grade \>=3 immune mediated AE related to prior immune modulatory therapy and required immunosuppressive therapy 2. Active or prior autoimmune disease that might deteriorate when receiving an immunostimulatory agent 3. History of uveitis within the preceding 6 months 4. Clinically significant Grade \>=3 neurodegenerative disease 5. Grade 3 or higher pulmonary disease unrelated to underlying malignancy 6. Previous exposure to an investigational immunostimulatory antibody conjugate or systemic TLR agonist

Locations (15)

Presbyterian/ St. Lukes Medical Center

Denver, Colorado, United States

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, United States

Smilow Cancer Hospital - Yale New Haven Health

New Haven, Connecticut, United States

Yale - New Haven Hospital - Yale Cancer Center

New Haven, Connecticut, United States

Smilow Cancer Hospital Phase 1 Unit

New Haven, Connecticut, United States

Smilow Cancer Hospital - Trumbull

Trumbull, Connecticut, United States

Community Health Network, Inc

Indianapolis, Indiana, United States

Community Health Network, Inc.

Indianapolis, Indiana, United States

Community Health Network, Inc.

Indianapolis, Indiana, United States

Community Health Network, Inc.

Indianapolis, Indiana, United States

...and 5 more locations

Outcomes

Primary Outcomes

Number of participants with adverse events (AEs)

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention

Time frame: Through 30-37 days after the last study treatment, up to approximately 2 years

Number of participants with laboratory abnormalities

Time frame: Through 30-37 days after the last study treatment, up to approximately 2 years

Number of dose modifications due to AEs

Time frame: Through end of treatment up to approximately 2 years

Number of participants with dose-limiting toxicities (DLTs)

Time frame: Up to 21 days

Number of participants with DLTs by dose level

Time frame: Up to 21 days

Secondary Outcomes

Pharmacokinetic (PK) parameter - Area under the concentration-time curve (AUC)

PK endpoint

Time frame: Through 30-37 days after the last study treatment, up to approximately 2 years

PK parameter - Maximum concentration (Cmax)

PK endpoint

Time frame: Through 30-37 days after the last study treatment, up to approximately 2 years

PK parameter - Time to maximum concentration (Tmax)

PK endpoint

Time frame: Through 30-37 days after the last study treatment, up to approximately 2 years

PK parameter - t1/2

PK endpoint

Time frame: Through 30-37 days after the last study treatment, up to approximately 2 years

PK parameter - Trough concentration (Ctrough)

PK endpoint

Time frame: Through 30-37 days after the last study treatment, up to approximately 2 years

Number of participants with antidrug antibodies (ADAs)

Time frame: Through 30-37 days after the last study treatment, up to approximately 2 years

Objective response rate (ORR)

The objective response rate (ORR) is defined as the percentage of participants with complete response (CR) or partial response (PR) which is subsequently confirmed as assessed according to Response Evaluation in Solid Tumors (RECIST) v1.1.

Time frame: Through end of study and up to approximately 2 years

Best overall response

The best overall response for a participant will be determined by the order of confirmed CR, confirmed PR, stable disease (SD), progressive disease (PD), not evaluable (NE) or not applicable (NA) per RECIST v1.1.

Time frame: Through end of study and up to approximately 2 years

Duration of response (DOR)

DOR is defined as the time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of tumor progression per RECIST v1.1 or to death due to any cause

Time frame: Through end of study and up to approximately 2 years

Progression-free survival (PFS)

PFS is defined as the time from start of PF-08046037 to first documentation of disease progression (based on radiographic assessments per RECIST v1.1) or death due to any cause, whichever comes first

Time frame: Through end of study and up to approximately 2 years

Overall survival (OS)

OS is defined as the time from start of PF-08046037 to date of death due to any cause

Time frame: Through end of study and up to approximately 2 years

Percent change of cells within tumors based on multiplex immunofluorescence

This measure will assess the number of immune cells, PD-1, PD-L1, and TLR7 expression within the tumor microenvironment.

Time frame: Through end of study and up to approximately 2 years

A Clinical Trial of PF-08046037 Alone or With Sasanlimab in Patients With Advanced or Metastatic Malignancies

Overview

Conditions

Interventions

Eligibility

Locations (15)

Outcomes

Primary Outcomes

Secondary Outcomes