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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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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

Intervention / Treatment
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* Biological: PF-07263689
* Biological: Sasanlimab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Monotherapy dose escalation (Part 1A)<br>Participants will receive PF-07263689 once a week for 4 doses | Biological: PF-07263689<br>* Genetically engineered oncolytic vaccinia virus<br>|
| Experimental: Combination dose escalation (Part 1B)<br>Participants will receive PF-07263689 intravenous (IV) once week for 4 doses in combination with sasanlimab subcutaneous (SC) once every 4 weeks | Biological: PF-07263689<br>* Genetically engineered oncolytic vaccinia virus<br>Biological: Sasanlimab<br>* A monoclonal antibody that blocks the interaction between PD-1 and PD-L1/ PD-L2<br>|
| Experimental: Dose expansion (Part 2) - Tumor specific Arm A<br>Participants will receive PF-07263689 IV once week for 4 doses in combination with sasanlimab SC once every 4 weeks | Biological: PF-07263689<br>* Genetically engineered oncolytic vaccinia virus<br>Biological: Sasanlimab<br>* A monoclonal antibody that blocks the interaction between PD-1 and PD-L1/ PD-L2<br>|
| Experimental: Dose expansion (Part 2) - Tumor specific Arm B<br>Participants will receive PF-07263689 IV once week for 4 doses in combination with sasanlimab SC once every 4 weeks | Biological: PF-07263689<br>* Genetically engineered oncolytic vaccinia virus<br>Biological: Sasanlimab<br>* A monoclonal antibody that blocks the interaction between PD-1 and PD-L1/ PD-L2<br>|
| Experimental: Dose expansion (Part 2) - Tumor specific Arm C<br>Participants will receive PF-07263689 IV once week for 4 doses in combination with sasanlimab SC once every 4 weeks | Biological: PF-07263689<br>* Genetically engineered oncolytic vaccinia virus<br>Biological: Sasanlimab<br>* A monoclonal antibody that blocks the interaction between PD-1 and PD-L1/ PD-L2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with dose limiting toxicities (DLTs) in Dose escalation (Part 1A and 1B) | DLTs will be evaluated in Part 1A and Part 1B. The number of DLTs will be used to determine the dose escalation decision and recommended dose for PF-07263689 | Baseline through 28 days after first dose | 
| Number of participants with adverse events |  | Baseline through up to 2 years | 
| Number of participants with clinically significant laboratory abnormalities |  | Baseline through 90 days after first dose | 
| Objective response rate in the dose expansion (Part 2) arms | Tumor response as assessed using RECIST 1.1 | Baseline through up to 2 years or until disease progression | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate in dose escalation (Part 1A and 1B) | Tumor response as assessed using RECIST 1.1 | Baseline through 2 years or disease progression | 
| Maximum concentration (Cmax) of viral load titer of PF-07263689 |  | Day 1 and Day 8 (days of dosing): Pre-dose, 0.5, 1, 4, 8, 25, 48, 72 hours post-dose; Day 15 and Day 22 (days of dosing): Pre-dose and 4 hours post-dose; and at 28 days after first dose | 
| Time to maximal plasma concentration (Tmax) of viral load titer after PF-07263689 dosing |  | Day 1 and Day 8 (days of dosing): Pre-dose, 0.5, 1, 4, 8, 25, 48, 72 hours post-dose; Day 15 and Day 22 (days of dosing): Pre-dose and 4 hours post-dose; and at 28 days after first dose | 
| Area under the Curve from time 0 to the last measurable timepoint (AUClast) of viral load titer after PF-07263689 dosing |  | Day 1 and Day 8 (days of dosing): Pre-dose, 0.5, 1, 4, 8, 25, 48, 72 hours post-dose; Day 15 and Day 22 (days of dosing): Pre-dose and 4 hours post-dose; and at 28 days after first dose | 
| Viral titers for vector shedding of PF-07263689 in saliva, urine, injection site swab, and swab from any spontaneous skin pox lesion |  | Baseline and during 30, 45, and 60 days after the last dose | 
| Sasanlimab trough concentration (Part 1B and 2) |  | Day 1 (pre-dose), 8, 15, and 22 of Cycle 1; and on Day 1 (pre-dose) of each subsequent cycle | 
| Incidence and titers of anti-IL2 antibodies and anti-drug antibody (ADA) against PF-07263689 and sasanlimab as applicable |  | Baseline through End of Treatment and up to about 2 years | 
| Anti-tumor activity (Part 2) | Disease control rate, duration of response, progression free survival, and time to progression as assessed by RECIST 1.1 | Baseline through up to 2 years or until disease progression | 
| Overall survival (Part 2) | Proportion of participants alive | Baseline through up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced malignancies