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

Pfizer

Status and phase: Not yet enrolling; Phase 1

Conditions: Carcinoma, Non Small Cell Lung; Malignant Melanoma; Carcinoma, Pancreatic Ductal; Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Treatments: Drug: PF-08046037; Drug: sasanlimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06974734

2025-521499-69-00 (EU Trial (CTIS) Number)

C5941001

Details and patient eligibility

About

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.

Enrollment: 399 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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399 participants in 6 patient groups

Part 1a

Experimental group

Description:

PF-08046037 monotherapy dose escalation

Treatment:

Drug: PF-08046037

Part 2a

Experimental group

Description:

PF-08046037 monotherapy dose optimization

Treatment:

Drug: PF-08046037

Part 3a

Experimental group

Description:

PF-08046037 monotherapy dose expansion

Treatment:

Drug: PF-08046037

Part 1b

Experimental group

Description:

PF-08046037 +sasanlimab dose escalation

Treatment:

Drug: sasanlimab

Drug: PF-08046037

Part 2b

Experimental group

Description:

PF-08046037 + sasanlimab dose optimization

Treatment:

Drug: sasanlimab

Drug: PF-08046037

Part 3b

Experimental group

Description:

PF-08046037 + sasanlimab dose expansion

Treatment:

Drug: sasanlimab

Drug: PF-08046037