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

• ClinicalTrials.gov Identifier: NCT05061537
• Recruitment Status: Terminated
• First Posted: September 29, 2021
• Last Update Posted: April 3, 2023
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

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 (Clinical Trial)
• Actual Enrollment: 13 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: October 20, 2021
• Actual Primary Completion Date: October 14, 2022
• Actual Study Completion Date: October 14, 2022

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) [ Time Frame: 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 [ Time Frame: Baseline through up to 2 years ]
3. Number of participants with clinically significant laboratory abnormalities [ Time Frame: Baseline through 90 days after first dose ]
4. Objective response rate in the dose expansion (Part 2) arms [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline and during 30, 45, and 60 days after the last dose ]
6. Sasanlimab trough concentration (Part 1B and 2) [ Time Frame: 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 [ Time Frame: Baseline through End of Treatment and up to about 2 years ]
8. Anti-tumor activity (Part 2) [ Time Frame: 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) [ Time Frame: Baseline through up to 2 years ]
   Proportion of participants alive

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

United States, California

City of Hope

Duarte, California, United States, 91010

United States, New York

Columbia University Medical Center

New York, New York, United States, 10032

CUMC Research Pharmacy

New York, New York, United States, 10032

Sponsors and Collaborators

Pfizer

Investigators

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

More Information

Additional Information:

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

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT05061537
• Other Study ID Numbers: C4651001; OBIR-2 ( Other Identifier: Alias Study Number )
• First Posted: September 29, 2021
• Last Update Posted: April 3, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

• 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; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Neoplasms by Histologic Type; Carcinoma; Neoplasms, Glandular and Epithelial; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urogenital Neoplasms; Urologic Neoplasms; Urologic Diseases; Male Urogenital Diseases; Adenocarcinoma; Kidney Neoplasms; Kidney Diseases; Liver Diseases