Clinical trial NCT05061537: Study of PF-07263689 in Participants With Selected Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
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
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2021-09-29
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Up to 28 days
measure: 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
timeFrame: 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)
measure: Part 1: Number of Participants With Treatment Emergent Adverse Events Based on Maximum Common Terminology Criteria for Adverse Events (CTCAE) Version 5 Grade
timeFrame: 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)
measure: Part 1: Number of Participants With Hematology Abnormalities by Maximum On-Treatment CTCAE Grade
timeFrame: 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)
measure: Part 1: Number of Participants With Clinical Chemistry Abnormalities by Maximum On-Treatment CTCAE Grade
timeFrame: 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)
measure: 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
timeFrame: 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)
measure: Part 2: Number of Participants With Treatment Emergent Adverse Events Based on Maximum CTCAE Version 5 Grade
timeFrame: 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)
measure: Part 2: Number of Participants With Laboratory Abnormalities by Maximum On-Treatment CTCAE Grade
timeFrame: 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)
measure: Part 2: Objective Response Rate
timeFrame: From first dose of study treatment until CR or PR (up to 2 years)
Secondary outcomes:
measure: Part 1: Objective Response Rate
timeFrame: From first dose of study treatment until CR or PR (up to maximum follow-up of 10.45 months)
measure: Part 1: Duration of Response
timeFrame: 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)
measure: Part 1: Progression Free Survival
timeFrame: 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)
measure: Part 1: Time to Progression
timeFrame: From start date of treatment to the date of first documentation of PD (up to maximum follow-up of 10.45 months)
measure: Part 1: Maximum Observed Concentration (Cmax) of PF-07263689 in Blood
timeFrame: 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)
measure: Part 1: Time to Maximum Concentration (Tmax) of PF-07263689 in Blood
timeFrame: 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)
measure: Part 1: Area Under the Concentration-Time Curve From Time 0 to Time of Last Measurable Concentration of PF-07263689 in Blood
timeFrame: 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)
measure: Part 1b: Trough Concentration of Sasanlimab
timeFrame: pre-dose on Day 1, 8, 15 and 22
measure: Part 1: Viral Titers in Saliva, Urine and Skin Swabs During 30, 45 and 60 Days After the Last PF-07263689 Dose
timeFrame: At 30, 45 and 60 days post last dose of study treatment (up to 24 days of treatment exposure)
measure: Part 1: Percentage of Participants With Positive Neutralizing Antibodies Against PF-07263689 and Sasanlimab
timeFrame: From Baseline (pre-dose) on Day 1 up to Day 22
measure: Part 1: Percentage of Participants With Positive Anti-interleukin 2 Antibodies
timeFrame: From Baseline (pre-dose) on Day 1 up to Day 22
measure: Part 2: Maximum Observed Concentration (Cmax) of PF-7263689 in Blood
timeFrame: 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)
measure: Part 2: Time to Maximum Concentration (Tmax) of PF-07263689 in Blood
timeFrame: 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)
measure: Part 2: Area Under the Concentration-Time Curve From Time 0 to Time of Last Measurable Concentration of PF-07263689 in Blood
timeFrame: 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)
measure: Part 2: Trough Concentration of Sasanlimab
timeFrame: Pre-dose on Day 1, 8, 15 and 22
measure: Part 2: Viral Titers in Saliva, Urine and Skin Swabs During 30, 45 and 60 Days After the Last PF-07263689 Dose
timeFrame: 30, 45 and 60 days after the last PF-07263689 dose
measure: Part 2: Percentage of Participants With Positive Anti-drug Antibodies Against PF-07263689 and Sasanlimab
timeFrame: From first dose of study treatment until 60 days after last dose of study treatment (up to 2 years)
measure: Part 2: Titer for Anti-PF-07263689 Antibody
timeFrame: From first dose of study treatment until 60 days after last dose of study treatment (up to 2 years)
measure: Part 2: Percentage of Participants With Positive Anti-interleukin 2 Antibodies
timeFrame: From first dose of study treatment until 60 days after last dose of study treatment (up to 2 years)
measure: Part 2: Titer for Anti-IL2 Antibodies
timeFrame: From first dose of study treatment until 60 days after last dose of study treatment (up to 2 years)
measure: Part 2: Disease Control Rate
timeFrame: From start of study treatment until CR, PR or SD (up to 2 years)
measure: Part 2: Duration of Response
timeFrame: From first documentation of CR or PR to date of first documentation of PD or death due to any cause (up to 2 years)
measure: Part 2: Progression Free Survival
timeFrame: From start date of treatment to the date of first documentation of PD or death due to any cause (up to 2 years)
measure: Part 2: Time to Progression
timeFrame: From start date of treatment to the date of first documentation of PD (up to 2 years)
measure: Part 2: Overall Survival
timeFrame: From start of study treatment to the date of death from any cause (up to 2 years)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: CUMC Research Pharmacy
state: New York
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: