Brief Title: PF-07263689 in Participants With Selected Advanced Solid Tumors

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)

Primary Outcome 1 - Timeframe: Up to 28 days

Primary Outcome 2 - Measure: Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)

Primary Outcome 2 - Timeframe: From first dose of study treatment until 90 days after last dose of study treatment or before start of new anti-cancer therapy (up to maximum of 10.45 months)

Primary Outcome 3 - Measure: Serious Adverse Events (SAEs)

Primary Outcome 3 - Timeframe: From first dose of study treatment until 90 days after last dose of study treatment or before start of new anti-cancer therapy (up to maximum of 10.45 months)

Primary Outcome 4 - Measure: Treatment Related Treatment Emergent Adverse Events and Treatment Related Serious Adverse Events

Primary Outcome 4 - Timeframe: From first dose of study treatment until 1 month follow-up (28+/-7) days after last dose of study treatment (up to 24 days of treatment exposure)

Primary Outcome 5 - Measure: Part 1: Number of Participants With Treatment Emergent Adverse Events Based on Maximum Common Terminology Criteria for Adverse Events (CTCAE) Version 5 Grade

Primary Outcome 5 - Timeframe: From first dose of study treatment until 1 month follow-up (28+/-7) days after last dose of study treatment (up to 24 days of treatment exposure)

Primary Outcome 6 - Measure: Part 1: Number of Participants With Hematology Abnormalities by Maximum On-Treatment CTCAE Grade

Primary Outcome 6 - Timeframe: From first dose of study treatment until 90 days after last dose of study treatment or before start of new anti-cancer therapy (up to 2 years)

Primary Outcome 7 - Measure: Part 1: Number of Participants With Clinical Chemistry Abnormalities by Maximum On-Treatment CTCAE Grade

Primary Outcome 7 - Timeframe: From first dose of study treatment until 90 days after last dose of study treatment or before start of new anti-cancer therapy (up to 2 years)

Primary Outcome 8 - Measure: Part 2: Number of Participants With Treatment Emergent Adverse Events

Primary Outcome 8 - Timeframe: From first dose of study treatment until 35 days after last dose of study treatment or before start of new anti-cancer therapy (up to 2 years)

Primary Outcome 9 - Measure: Serious Adverse Events

Primary Outcome 9 - Timeframe: From first dose of study treatment until CR or PR (up to 2 years)

Primary Outcome 10 - Measure: Treatment Related Treatment Emergent Adverse Events and Treatment Related Serious Adverse Events

Primary Outcome 10 - Timeframe: N/A

Primary Outcome 11 - Measure: Part 2: Number of Participants With Treatment Emergent Adverse Events Based on Maximum CTCAE Version 5 Grade

Primary Outcome 11 - Timeframe: N/A

Primary Outcome 12 - Measure: Part 2: Number of Participants With Laboratory Abnormalities by Maximum On-Treatment CTCAE Grade

Primary Outcome 12 - Timeframe: N/A

Primary Outcome 13 - Measure: Part 2: Objective Response Rate

Primary Outcome 13 - Timeframe: N/A

CONDITION

• Renal Cell Cancer
• Melanoma
• Non-Small-Cell Lung Cancer
• Hepatocellular Cancer
• Bladder Cancer
• Sarcoma
• Head and Neck Cancer
• Colorectal Cancer
• Ovarian Cancer
• Squamous Cell Carcinoma

ELIGIBILITY

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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Pfizer CT.gov Call Center

Role: Study Director

Affiliation: Pfizer

Overall Contact

Name: N/A

Phone: N/A

Email: N/A

LOCATION