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

NCT05061537 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: C4651001OBIR-2
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 3

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.

Conditions

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

Keywords

Advanced malignancies

Outcome Measures

Primary Outcomes (9)

• 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 Outcomes (25)

• Part 1: Objective Response Rate

  From first dose of study treatment until CR or PR (up to maximum follow-up of 10.45 months)

• Part 1: Duration of Response

  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

  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

  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)

Study Arms (5)

Monotherapy dose escalation (Part 1A)

EXPERIMENTAL

Participants will receive PF-07263689 once a week for 4 doses

Biological: PF-07263689

Combination dose escalation (Part 1B)

EXPERIMENTAL

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; Biological: Sasanlimab

Dose expansion (Part 2) - Tumor specific Arm A

EXPERIMENTAL

Participants will receive PF-07263689 IV once week for 4 doses in combination with sasanlimab SC once every 4 weeks

Biological: PF-07263689; Biological: Sasanlimab

Dose expansion (Part 2) - Tumor specific Arm B

EXPERIMENTAL

Participants will receive PF-07263689 IV once week for 4 doses in combination with sasanlimab SC once every 4 weeks

Biological: PF-07263689; Biological: Sasanlimab

Dose expansion (Part 2) - Tumor specific Arm C

EXPERIMENTAL

Participants will receive PF-07263689 IV once week for 4 doses in combination with sasanlimab SC once every 4 weeks

Biological: PF-07263689; Biological: Sasanlimab

Interventions

PF-07263689 BIOLOGICAL

Genetically engineered oncolytic vaccinia virus

Combination dose escalation (Part 1B); Dose expansion (Part 2) - Tumor specific Arm A; Dose expansion (Part 2) - Tumor specific Arm B; Dose expansion (Part 2) - Tumor specific Arm C; Monotherapy dose escalation (Part 1A)

Sasanlimab BIOLOGICAL

A monoclonal antibody that blocks the interaction between PD-1 and PD-L1/ PD-L2

Combination dose escalation (Part 1B); Dose expansion (Part 2) - Tumor specific Arm A; Dose expansion (Part 2) - Tumor specific Arm B; Dose expansion (Part 2) - Tumor specific Arm C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (3)

City of Hope

Duarte, California, 91010, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

CUMC Research Pharmacy

New York, New York, 10032, United States

Location

Related Links

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

MeSH Terms

Conditions

Carcinoma, Renal Cell; Melanoma; Carcinoma, Non-Small-Cell Lung; Liver Neoplasms; Urinary Bladder Neoplasms; Sarcoma; Head and Neck Neoplasms; Colorectal Neoplasms; Ovarian Neoplasms; Carcinoma, Squamous Cell

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Urinary Bladder Diseases; Neoplasms, Connective and Soft Tissue; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Neoplasms, Squamous Cell

Limitations and Caveats

Data was not collected for Part 1B and Part 2 as no participants were enrolled due to early termination.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquires@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2021
• First Posted: September 29, 2021
• Study Start: October 20, 2021
• Primary Completion: October 14, 2022
• Study Completion: October 14, 2022
• Last Updated: April 12, 2024
• Results First Posted: April 12, 2024

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)