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

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05061537
• Other study ID #: C4651001
• Secondary ID: OBIR-2
• Status: Terminated
• Phase: Phase 1
• Start date: October 20, 2021
• Est. completion date: October 14, 2022

Study information

• Verified date: October 2023
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 13
• Est. completion date: October 14, 2022
• Est. primary completion date: October 14, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bladder Cancer
• Carcinoma, Hepatocellular
• Carcinoma, Renal Cell
• Colorectal Cancer
• Head and Neck Cancer
• Hepatocellular Cancer
• Liver Neoplasms
• Melanoma
• Non-Small-Cell Lung Cancer
• Ovarian Cancer
• Renal Cell Cancer
• Sarcoma
• Squamous Cell Carcinoma

Intervention

Biological:
• PF-07263689
Genetically engineered oncolytic vaccinia virus
• Sasanlimab
A monoclonal antibody that blocks the interaction between PD-1 and PD-L1/ PD-L2

Locations

Country	Name	City	State
United States	City of Hope	Duarte	California
United States	Columbia University Medical Center	New York	New York
United States	CUMC Research Pharmacy	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Part 1b: Trough Concentration of Sasanlimab		pre-dose on Day 1, 8, 15 and 22
Secondary	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)
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Part 2: Trough Concentration of Sasanlimab		Pre-dose on Day 1, 8, 15 and 22
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)

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