Study of PF-07263689 in Participants With Selected Advanced Solid Tumors

A PHASE 1, OPEN-LABEL, DOSE ESCALATION AND EXPANSION STUDY EVALUATING THE SAFETY AND PHARMACODYNAMICS OF PF-07263689, EITHER ALONE OR IN COMBINATION WITH AN ANTI-PD-1 ANTIBODY, IN PREVIOUSLY TREATED PARTICIPANTS WITH SELECTED LOCALLY ADVANCED OR METASTATIC SOLID TUMORS

This is a first-in-human, Phase 1, open label, multicenter, multiple dose, dose escalation and expansion study intended to evaluate the safety, viral load kinetics and shedding, pharmacodynamic, and anti-tumor activity of PF-07263689, either alone or in combination with sasanlimab (an investigational anti-programmed cell death protein 1 [PD-1] antibody), in patients with selected locally advanced or metastatic solid tumors who have exhausted all available standard of care therapies available to them.

The study consists of 2 parts: Part 1 dose escalation for PF-07263689 monotherapy (Part 1A) and in combination with sasanlimab (Part 1B), followed by Part 2 dose expansion for the combination therapy.

Inclusion Criteria:

• Histological or cytological diagnosis of locally advanced or metastatic solid tumors known to have approved therapies using immune checkpoint inhibitors or anti-vascular endothelial growth factor agents
• Have exhausted (or refuse) all available standard of care therapy (e.g., including anti-PD1/programmed death ligand 1 [PDL1] if applicable) or for whom no standard therapy is available for their tumor type
• Patients with prior anti-PD1/PDL1 must have documentation of primary or secondary resistance to last prior anti-PD1/PDL1 therapy according to Immunotherapy Resistance Committee (SITC) (Kluger et al, 2020)
• Have at least 1 measurable lesion by RECIST 1.1 that has not been previously irradiated (for Part 2 only)
• Have recently obtained archival tumor tissue sample available, or undergo de novo tumor biopsy
• Eastern Cooperative Oncology Group (ECOG) PS 0-1
• Adequate hematologic, renal, and liver functions
• Dose Escalation (Part 1A and 1B): Any advanced or metastatic solid tumor fulfilling other relevant eligibility criteria.
• Dose Expansion (Part 2): Tumor specific cohorts (NSCLC, RCC, melanoma, MSS CRC) must have received prior approved therapies (Part 2)

Exclusion Criteria:

• Other active malignancy
• Recent major surgery
• Systemic anticancer therapy and chemotherapy within protocol-defined washout period
• Known or suspected hypersensitivity to prior treatment with any vaccinia oncolytic, pox virus, or antiviral agents within the past 10 years
• Current or history of myocarditis or congestive heart failure (New York Heart Association [NYHA] III-IV); unstable angina; or serious uncontrolled arrhythmia or recent myocardial infarction
• Active or history of interstitial lung disease (ILD)/pneumonitis
• Patients requiring chronic systemic immunosuppressants
• History of severe immune mediated side effect that was considered related to prior immune modulatory therapy and requiring immunosuppressive therapy
• Known symptomatic brain metastases requiring steroids
• History of or ongoing severe inflammatory skin conditions or severe eczema having required medical treatment
• Any prior or planned organ transplant
• Presence of any open, active wound requiring treatment