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

• Sponsor: Pfizer (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05061537
• Collaborator: (none)
• Enrollment: 120
• Locations: 6
• Arms: 5
• Anticipated Duration (Months): 41.9
• Patients Per Site: 20
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
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	Biological: PF-07263689; Biological: Sasanlimab	Phase 1

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 120 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Oct 20, 2021
• Anticipated Primary Completion Date: Apr 18, 2025
• Anticipated Study Completion Date: Apr 18, 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Number of participants with dose limiting toxicities (DLTs) in Dose escalation (Part 1A and 1B) [Baseline through 28 days after first dose]

   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

2. Number of participants with adverse events [Baseline through up to 2 years]

3. Number of participants with clinically significant laboratory abnormalities [Baseline through 90 days after first dose]

4. Objective response rate in the dose expansion (Part 2) arms [Baseline through up to 2 years or until disease progression]

   Tumor response as assessed using RECIST 1.1

Secondary Outcome Measures

1. Objective response rate in dose escalation (Part 1A and 1B) [Baseline through 2 years or disease progression]

   Tumor response as assessed using RECIST 1.1

2. 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]

3. 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]

4. 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]

5. 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]

6. 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]

7. 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]

8. Anti-tumor activity (Part 2) [Baseline through up to 2 years or until disease progression]

   Disease control rate, duration of response, progression free survival, and time to progression as assessed by RECIST 1.1

9. Overall survival (Part 2) [Baseline through up to 2 years]

   Proportion of participants alive

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010
2	The University of Louisville, James Graham Brown Cancer Center	Louisville	Kentucky	United States	40202
3	UMC Health Care Outpatient Center (For Imaging)	Louisville	Kentucky	United States	40202
4	University of Louisville Hospital	Louisville	Kentucky	United States	40202
5	Columbia University Medical Center	New York	New York	United States	10032
6	CUMC Research Pharmacy	New York	New York	United States	10032

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT05061537
• Other Study ID Numbers: C4651001; OBIR-2
• First Posted: Sep 29, 2021
• Last Update Posted: Aug 23, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Pfizer: Advanced malignancies
• Additional relevant MeSH terms: Carcinoma, Renal Cell; Liver Neoplasms; Carcinoma, Hepatocellular

Study Results

No Results Posted as of Aug 23, 2022