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.

Study Overview

• Status: Terminated
• Conditions: Melanoma; Sarcoma; Head and Neck Cancer; Colorectal Cancer; Ovarian Cancer; Bladder Cancer; Renal Cell Cancer; Hepatocellular Cancer; Squamous Cell Carcinoma; Non-Small-Cell Lung Cancer
• Intervention / Treatment: Biological: PF-07263689; Biological: Sasanlimab

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10032
      • CUMC Research Pharmacy

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)	DLTs=occurrence of any of following adverse events (AEs) attributable to PF-07263689 in first cycle (cycle=28 days): Hematologic: grade(G)4 neutropenia lasting >5 days; febrile neutropenia; G3 neutropenia with infection, thrombocytopenia with bleeding; G4 thrombocytopenia. Non-hematologic: any treatment-related G>=3 toxicity; clinical events consistent with Hy's law; any G3 cytokine release syndrome (CRS) not improving to G<=2 within 72 hours despite medical management; any G4 CRC; G>=3 toxicity of any duration affecting vital organs; G4 vaccinia infection lasting >=6 days; G>=3 toxicities persisting for >3 days despite medical therapy (e.g. nausea, vomiting, diarrhea, fatigue); G >=3 rash not resolving to G<2 within 21 days with supportive measures; G>=3 lab abnormalities not controlled to G <=2 with or without appropriate medical management within 3 days; treatment-related AE inducing a delay by 2 weeks in receiving next scheduled dose; clinically important or persistent toxicities.	Up to 28 days
Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Treatment Related Treatment Emergent Adverse Events and Treatment Related Serious Adverse Events	An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was defined as any untoward medical occurrence that at any dose met 1 or more of the following criteria: resulted in death, was life-threatening; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic; an important medical event; required inpatient hospitalization or prolongation of existing hospitalization. TEAE was defined as any adverse event that occurred during the on-treatment period, on or after the first dose of study treatment. Relatedness was based on investigator's assessment.	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)
Part 1: Number of Participants With Treatment Emergent Adverse Events Based on Maximum Common Terminology Criteria for Adverse Events (CTCAE) Version 5 Grade	An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAE was defined as any AE that occurred during the on-treatment period, on or after the first dose of study treatment. AEs were graded using CTCAE version 5 where, grade 1=mild AE; grade 2=moderate AE; grade 3=severe AE; grade 4= life-threatening; urgent intervention indicated; and grade 5= death related to AE.	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)
Part 1: Number of Participants With Hematology Abnormalities by Maximum On-Treatment CTCAE Grade	Hematology abnormalities were graded using CTCAE version 5 where, grade 0=non-missing lab value outside the grading range for the corresponding lab parameter; grade 1=mild; grade 2=moderate; grade 3=severe; grade 4= life-threatening. Only those categories with non-zero values for any of the arms have been reported.	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)
Part 1: Number of Participants With Clinical Chemistry Abnormalities by Maximum On-Treatment CTCAE Grade	Clinical chemistry abnormalities were graded using CTCAE version 5 where, grade 0=non-missing lab value outside the grading range for the corresponding lab parameter; grade 1=mild; grade 2=moderate; grade 3=severe; grade 4= life-threatening. Only those categories with non-zero values for any of the arms have been reported.	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)
Part 2: Number of Participants With Treatment Emergent Adverse Events, Serious Adverse Events, Treatment Related Treatment Emergent Adverse Events and Treatment Related Serious Adverse Events	An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was defined as any untoward medical occurrence that at any dose met 1 or more of the following criteria: resulted in death, was life-threatening; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic; an important medical event; required inpatient hospitalization or prolongation of existing hospitalization. TEAE was defined as any adverse event that occurred during the on-treatment period, on or after the first dose of study treatment. Relatedness was planned to be assessed by investigator.	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)
Part 2: Number of Participants With Treatment Emergent Adverse Events Based on Maximum CTCAE Version 5 Grade	AEs were planned to be graded using CTCAE version 5 where, grade 1=mild AE; grade 2=moderate AE; grade 3=severe AE; grade 4= life-threatening; urgent intervention indicated; and grade 5= death related to AE.	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)
Part 2: Number of Participants With Laboratory Abnormalities by Maximum On-Treatment CTCAE Grade	Hematology and clinical chemistry parameters were planned to be assessed.	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)
Part 2: Objective Response Rate	ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) and was determined using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 millimeter [mm] short axis), PR: at least 30 percent (%) decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. Short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions.	From first dose of study treatment until CR or PR (up to 2 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Objective Response Rate	ORR was defined as the percentage of participants with a best overall response of CR or PR and was determined using RECIST version 1.1. CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. Short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. 95% confidence interval (CI) was based on Clopper-Pearson method.	From first dose of study treatment until CR or PR (up to maximum follow-up of 10.45 months)
Part 1: Duration of Response	Duration of response was defined as the time from first documentation of CR or PR to date of first documentation of progressive disease (PD) or death due to any cause. CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non- pathological in size (<10 mm short axis), PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. Short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. PD: 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm and unequivocal progression of pre-existing lesions.	From first documentation of CR or PR to date of first documentation of PD or death due to any cause (up to maximum follow-up of 10.45 months)
Part 1: Progression Free Survival	Progression free survival was defined as time from start date of treatment to the date of first documentation of PD or death due to any cause. PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm and unequivocal progression of pre-existing lesions. 95% CI was based on Brookmeyer and Crowley method.	From start date of treatment to the date of first documentation of PD or death due to any cause (up to maximum follow-up of 10.45 months)
Part 1: Time to Progression	Time to progression was defined as the time from start date of treatment to the date of the first documentation of PD. PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm and unequivocal progression of pre-existing lesions. 95% CI was based on Brookmeyer and Crowley method.	From start date of treatment to the date of first documentation of PD (up to maximum follow-up of 10.45 months)
Part 1: Maximum Observed Concentration (Cmax) of PF-07263689 in Blood		Day 1 (pre-dose, 0.5, 1, 4, 8 hours post-dose), Day 2, Day 3, Day 4, Day 8 (pre-dose, 0.5, 1, 4, 8 hours post-dose), Day 9, Day 10, Day 15 and 22 (pre-dose and 4 hours post-dose)
Part 1: Time to Maximum Concentration (Tmax) of PF-07263689 in Blood		Day 1 (pre-dose, 0.5, 1, 4, 8 hours post-dose), Day 2, Day 3, Day 4, Day 8 (pre-dose, 0.5, 1, 4, 8 hours post-dose), Day 9, Day 10, Day 15 and 22 (pre-dose and 4 hours post-dose)
Part 1: Area Under the Concentration-Time Curve From Time 0 to Time of Last Measurable Concentration of PF-07263689 in Blood		Day 1 (pre-dose, 0.5, 1, 4, 8 hours post-dose), Day 2, Day 3, Day 4, Day 8 (pre-dose, 0.5, 1, 4, 8 hours post-dose), Day 9, Day 10, Day 15 and 22 (pre-dose and 4 hours post-dose)
Part 1b: Trough Concentration of Sasanlimab		pre-dose on Day 1, 8, 15 and 22
Part 1: Viral Titers in Saliva, Urine and Skin Swabs During 30, 45 and 60 Days After the Last PF-07263689 Dose	Viral titers in each matrix (saliva, urine and skin swabs [30 days post last dose only]) at 30, 45 and 60 days after last dose of study treatment is reported in this outcome measure.	At 30, 45 and 60 days post last dose of study treatment (up to 24 days of treatment exposure)
Part 1: Percentage of Participants With Positive Neutralizing Antibodies Against PF-07263689 and Sasanlimab	A participant was considered NAb positive if (1) baseline titer was missing or negative and participant had >= 1 post-treatment positive titer (treatment-induced) or (2) positive titer at baseline and had a ratio of >= 4 in titer (dilution) to baseline in >= 1 post-treatment sample (treatment-boosted). Percentage of participants with positive neutralizing antibodies against PF-07263689 is presented in this outcome measure. Data was not collected for sasanlimab as no participants were enrolled in Part 1b of the study.	From Baseline (pre-dose) on Day 1 up to Day 22
Part 1: Percentage of Participants With Positive Anti-interleukin 2 Antibodies	A participant was considered anti-drug antibody (ADA) positive if (1) baseline titer was missing or negative and participant had >= 1 post-treatment positive titer (treatment-induced) or (2) positive titer at baseline and had a ratio of >= 4 in titer (dilution) to baseline in >= 1 post-treatment sample (treatment-boosted). Percentage of participants with positive anti-interleukin 2 antibodies against PF-07263689 is presented in this outcome measure.	From Baseline (pre-dose) on Day 1 up to Day 22
Part 2: Maximum Observed Concentration (Cmax) of PF-7263689 in Blood		Day 1 (pre-dose, 0.5, 1, 4, 8 hours post-dose), Day 2, Day 3, Day 4, Day 8 (pre-dose, 0.5, 1, 4, 8 hours post-dose), Day 9, Day 10, Day 15 and 22 (pre-dose and 4 hours post-dose)
Part 2: Time to Maximum Concentration (Tmax) of PF-07263689 in Blood		Day 1 (pre-dose, 0.5, 1, 4, 8 hours post-dose), Day 2, Day 3, Day 4, Day 8 (pre-dose, 0.5, 1, 4, 8 hours post-dose), Day 9, Day 10, Day 15 and 22 (pre-dose and 4 hours post-dose)
Part 2: Area Under the Concentration-Time Curve From Time 0 to Time of Last Measurable Concentration of PF-07263689 in Blood		Day 1 (pre-dose, 0.5, 1, 4, 8 hours post-dose), Day 2, Day 3, Day 4, Day 8 (pre-dose, 0.5, 1, 4, 8 hours post-dose), Day 9, Day 10, Day 15 and 22 (pre-dose and 4 hours post-dose)
Part 2: Trough Concentration of Sasanlimab		Pre-dose on Day 1, 8, 15 and 22
Part 2: Viral Titers in Saliva, Urine and Skin Swabs During 30, 45 and 60 Days After the Last PF-07263689 Dose		30, 45 and 60 days after the last PF-07263689 dose
Part 2: Percentage of Participants With Positive Anti-drug Antibodies Against PF-07263689 and Sasanlimab		From first dose of study treatment until 60 days after last dose of study treatment (up to 2 years)
Part 2: Titer for Anti-PF-07263689 Antibody		From first dose of study treatment until 60 days after last dose of study treatment (up to 2 years)
Part 2: Percentage of Participants With Positive Anti-interleukin 2 Antibodies		From first dose of study treatment until 60 days after last dose of study treatment (up to 2 years)
Part 2: Titer for Anti-IL2 Antibodies		From first dose of study treatment until 60 days after last dose of study treatment (up to 2 years)
Part 2: Disease Control Rate	Disease control rate was the percentage of participants with CR, PR or stable disease (SD), as defined by RECIST 1.1. CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. Short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. SD: Does not qualify for CR, PR, or progression. All target lesions assessed.	From start of study treatment until CR, PR or SD (up to 2 years)
Part 2: Duration of Response	Duration of response was defined as the time from first documentation of CR or PR to date of first documentation of progressive disease (PD) or death due to any cause. CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non- pathological in size (<10 mm short axis), PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. Short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. PD: 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm and unequivocal progression of pre-existing lesions.	From first documentation of CR or PR to date of first documentation of PD or death due to any cause (up to 2 years)
Part 2: Progression Free Survival	Progression free survival was defined as time from start date of treatment to the date of first documentation of PD or death due to any cause. PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm and unequivocal progression of pre-existing lesions.	From start date of treatment to the date of first documentation of PD or death due to any cause (up to 2 years)
Part 2: Time to Progression	Time to progression was defined as the time from start date of treatment to the date of the first documentation of PD. PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm and unequivocal progression of pre-existing lesions.	From start date of treatment to the date of first documentation of PD (up to 2 years)
Part 2: Overall Survival	Overall survival was defined as the duration from the start of study treatment to the date of death from any cause.	From start of study treatment to the date of death from any cause (up to 2 years)

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2021
• Primary Completion (Actual): October 14, 2022
• Study Completion (Actual): October 14, 2022

Study Registration Dates

• First Submitted: September 22, 2021
• First Submitted That Met QC Criteria: September 22, 2021
• First Posted (Actual): September 29, 2021

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: October 9, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Advanced malignancies
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Kidney Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carcinoma, Renal Cell; Carcinoma, Hepatocellular; Liver Neoplasms
• Other Study ID Numbers: C4651001; OBIR-2 (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No