Clinical trial NCT06974734: A Clinical Trial of PF-08046037 Alone or With Sasanlimab in Patients With Advanced or Metastatic Malignancies
Official title: AN OPEN-LABEL PHASE 1 STUDY TO EVALUATE PF-08046037 AS MONOTHERAPY AND PART OF COMBINATION THERAPY IN PARTICIPANTS WITH ADVANCED MALIGNANCIES
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Carcinoma, Non Small Cell Lung
Carcinoma, Pancreatic Ductal
Malignant Melanoma
Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Keywords: Advanced solid tumors
NSCLC
PDAC
HNSCC
ISAC
ADC
PD-L1 inhibitor
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2025-05-16
Enrollment: 399
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Dose escalation and expansion
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with adverse events (AEs)
timeFrame: Through 30-37 days after the last study treatment, up to approximately 2 years
measure: Number of participants with laboratory abnormalities
timeFrame: Through 30-37 days after the last study treatment, up to approximately 2 years
measure: Number of dose modifications due to AEs
timeFrame: Through end of treatment up to approximately 2 years
measure: Number of participants with dose-limiting toxicities (DLTs)
timeFrame: Up to 21 days
measure: Number of participants with DLTs by dose level
timeFrame: Up to 21 days
Secondary outcomes:
measure: Pharmacokinetic (PK) parameter - Area under the concentration-time curve (AUC)
timeFrame: Through 30-37 days after the last study treatment, up to approximately 2 years
measure: PK parameter - Maximum concentration (Cmax)
timeFrame: Through 30-37 days after the last study treatment, up to approximately 2 years
measure: PK parameter - Time to maximum concentration (Tmax)
timeFrame: Through 30-37 days after the last study treatment, up to approximately 2 years
measure: PK parameter - t1/2
timeFrame: Through 30-37 days after the last study treatment, up to approximately 2 years
measure: PK parameter - Trough concentration (Ctrough)
timeFrame: Through 30-37 days after the last study treatment, up to approximately 2 years
measure: Number of participants with antidrug antibodies (ADAs)
timeFrame: Through 30-37 days after the last study treatment, up to approximately 2 years
measure: Objective response rate (ORR)
timeFrame: Through end of study and up to approximately 2 years
measure: Best overall response
timeFrame: Through end of study and up to approximately 2 years
measure: Duration of response (DOR)
timeFrame: Through end of study and up to approximately 2 years
measure: Progression-free survival (PFS)
timeFrame: Through end of study and up to approximately 2 years
measure: Overall survival (OS)
timeFrame: Through end of study and up to approximately 2 years
measure: Percent change of cells within tumors based on multiplex immunofluorescence
timeFrame: Through end of study and up to approximately 2 years
Other outcomes:
Locations:
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: Rio Piedras
country: Puerto Rico
facility: Pan American Center for Oncology Trials, LLC
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: