Study of PF-07265807 in Participants With Metastatic Solid Tumors.

Phase 1TerminatedNCT04458259

Pfizer88 enrolled

Overview

A First-in-Human Pharmacokinetic, Safety, and Tolerability Study of PF-07265807 as Monotherapy and in Combination in Participants with Advanced or Metastatic Solid Tumors

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Neoplasm Metastasis

Interventions

PF-07265807DRUG

Given 2 weeks on/1 week off

SasanlimabDRUG

Given SC Q3W

AxitinibDRUG

Dosed per package label starting with 5 mg PO BID

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * At least one measurable (Parts 1-4) or non-measurable lesion (Parts 1-3), not previously irradiated, as defined by RECIST 1.1 * ECOG Performance Status 0 or 1, 2 with approval * Adequate Bone Marrow Function * Adequate Renal Function * Adequate Liver Function * Resolved acute effects of any prior therapy * Able to provide adequate archival tumor tissue or freshly obtained tumor tissue (some participants will require mandatory pre- and on-treatment biopsy is part of the biomarker cohort). * Life expectancy of at least 3 months. * Part 1 and Part 2: Participants who are intolerant or resistant to standard treatment for selected solid tumors. * Part 3: Participants with advanced/metastatic RCC with a clear cell component and progressed with no standard therapy available. * Part 4, Cohort 1: Participants with NSCLC with METex14-skipping alteration(s) and progressed on at least 1 prior therapy. * Part 4, Cohort 2: Participants with MSS CRC with intermediate TMB and progressed with no satisfactory alternative treatment available, but has not received prior treatment with an anti-PD-(L)1 therapy. * Part 4, Cohort 3: Participants with metastatic gastric or GEJ adenocarcinoma that is PD-L1 positive that has progressed on at least 2 but no more than 3 prior chemotherapy regiments, but has not received prior treatment with an anti-PD-(L)1 therapy. * Part 4, Cohort 4: Participants with metastatic RCC with a clear cell component with IMDC intermediate or poor risk that have not received any prior systemic therapy for metastatic disease. Exclusion Criteria: * Known active uncontrolled or symptomatic CNS metastases. * Any other active malignancy within 2 years prior to enrollment. * Major surgery within 6 weeks, radiation therapy within 4 weeks, systemic anti-cancer therapy within 2 week or 5 half-lives (4 weeks or 5 half-lives for antibody therapies or investigational drug(s) taken on another study) prior to study entry. * Active or history of autoimmune disease requiring \>10mg/day prednisone or other concurrent immunosuppressive therapy. * Active, uncontrolled infection (controlled HBV, HCV, HIV/AIDS may be allowed) as defined in protocol. * Retinal or other serious ophthalmic disorders as defined in protocol. * Clinically significant cardiac disease as defined in protocol. * Uncontrolled HTN that cannot be controlled by medications. * Inability to consume or absorb study drug. * Known or suspected hypersensitivity to PF-07265807. * Prohibited concomitant medications as defined in protocol. * Active inflammatory GI disease, uncontrollable chronic diarrhea, or previous gastric resection or lap band surgery affecting absorption. * Active bleeding disorder. * Discontinuation of prior checkpoint inhibitor for treatment-related toxicity. * Experienced \>= G3 treatment-related irAE with prior PD-(L)1 agent. * Prior treatment with selective AXL/MERTK inhibitors For participants receiving sasanlimab: \- Known history of non-infectious pneumonitis that required steroid treatment or current pneumonitis.

Locations (33)

Outcomes

Primary Outcomes

Parts 1, 2, and 3: Number of participants with dose limiting toxicities (DLTs)

DLTs will be evaluated during the first cycle (day 21) or two cycles (day 42). The number of DLTs will be used to determine the maximum tolerated dose (MTD)

Time frame: Baseline through day 21 or 42

Parts 1, 2 and 3: Number of participants with treatment emergent adverse events (AEs)

AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy

Time frame: Baseline through approximately 2 years

Parts 1, 2, and 3: Number of participants with laboratory abnormalities

Laboratory abnormalities as characterized by type, frequency, severity, and timing.

Time frame: Baseline through approximately 2 years

Part 4: Overall Response Rate (ORR)

Response will be evaluable via radiographical tumor assessment by RECIST v1.1

Time frame: Baseline through approximately 2 years

Part 4, Cohort 4: Complete Response (CR)

Response will be evaluated via radiographical tumor assessment by RECIST v1.1

Time frame: Baseline through approximately 2 years

Secondary Outcomes

Parts 1, 2, and 3: Maximum plasma concentration (Cmax) of PF-07265807 and its metabolite

Single dose (Cmax) and multiple dose (assuming steady state is achieved; Cmax,ss) pharmacokinetic (PK) parameters of PF-07265807 and its metabolite

Time frame: Each cycle is 21 days. Cycle 1 Days 1 and 14, predose, 0.5,1,2,4,8 and 24 (if daily dosing) hours post dose; Cycle 1 Day 7, Cycle 2 Days 1 and 14 predose and 2 hours post dose; Cycle 3 Days 1 and 14 predose

Data from ClinicalTrials.gov

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Henry Eye Clinic

Fayetteville, Arkansas, United States

Highlands Oncology Group

Fayetteville, Arkansas, United States

Highlands Oncology Group

Rogers, Arkansas, United States

Highlands Oncology Group

Springdale, Arkansas, United States

UCI Chao Family Comprehensive Cancer Center

Orange, California, United States

Clinical & Translational Science Institute

San Francisco, California, United States

UCSF Helen Diller Family Comprehensive Cancer Center - Mission Hall

San Francisco, California, United States

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Rocky Mountain Lions Eye Institute (RMLEI)

Aurora, Colorado, United States

University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)

Aurora, Colorado, United States

...and 23 more locations

Parts 2 and 3: Maximum plasma concentration (Cmax) of sasanlimab

Single dose (Cmax) pharmacokinetic (PK) parameters of sasanlimab

Time frame: Through study completion, an average of 1 year

Part 3: Maximum plasma concentration at steady state (Cmax,ss) of axitinib

Multiple dose (assuming steady state is achieved; Cmax,ss) pharmacokinetic (PK) parameters of axitinib

Time frame: Each cycle is 21 days. Cycle 1 Day 1 predose; Cycle 1 Day 14 predose, 0.5,1,2,4, and 8 hours post dose

Parts 1, 2, and 3: Time to reach maximum plasma concentration (Tmax) of PF-07265807 and its metabolite

Single dose (Tmax) and multiple dose (assuming steady state is achieved; Tmax,ss) pharmacokinetic parameters of PF-07265807 and its metabolite

Parts 2 and 3: Time to reach maximum plasma concentration (Tmax) of sasanlimab

Single dose (Tmax) pharmacokinetic parameters of sasanlimab

Time frame: Through study completion, an average of 1 year

Part 3: Time to reach maximum plasma concentration at steady state (Tmax,ss) of axitinib

Multiple dose (assuming steady state is achieved; Tmax,ss) pharmacokinetic parameters of axitinib

Time frame: Each cycle is 21 days. Cycle 1 Day 1 predose; Cycle 1 Day 14 predose, 0.5,1,2,4, and 8 hours post dose

Parts 1, 2, and 3: Area under the curve from the time of dose to the last measurable concentration (AUClast) of PF-07265807 and its metabolite

Single dose (AUClast) pharmacokinetic parameters of PF-07265807 and its metabolite

Parts 2 and 3: Area under the curve from the time of dose to the last measurable concentration (AUClast) of sasanlimab

Single dose (AUClast) pharmacokinetic parameters of sasanlimab

Time frame: Through study completion, an average of 1 year

Parts 1, 2, and 3: Area under the curve from the time of dose to the time of the subsequent dose (AUCtau) at steady state of PF-07265807 and its metabolite

Multiple dose assuming steady state is achieved (AUCtau,ss) pharmacokinetic parameters of PF-07265807 and its metabolite

Part 3: Area under the curve from the time of dose to the time of the subsequent dose (AUCtau) at steady state of axitinib

Multiple dose assuming steady state is achieved (AUCtau,ss) pharmacokinetic parameters of axitinib

Time frame: Each cycle is 21 days. Cycle 1 Day 1 predose; Cycle 1 Day 14 predose, 0.5,1,2,4, and 8 hours post dose

Parts 1, 2, and 3: Terminal elimination half-life (t1/2) of PF-07265807 and its metabolite

As data permits, single dose (t1/2) pharmacokinetic parameters of PF-07265807 and its metabolite

Parts 2 and 3: Terminal elimination half-life (t1/2) of sasanlimab

As data permits, single dose (t1/2) pharmacokinetic parameters of sasanlimab

Time frame: Through study completion, an average of 1 year

Parts 1, 2, and 3: Area under the curve from the time of dose extrapolated to infinity (AUCinf) of PF-07265807 and its metabolite

As data permits, single dose (AUCinf) pharmacokinetic parameters of PF-07265807 and its metabolite

Parts 2 and 3: Area under the curve from the time of dose extrapolated to infinity (AUCinf) of sasanlimab

As data permits, single dose (AUCinf) pharmacokinetic parameters of sasanlimab

Time frame: Through study completion, an average of 1 year

Parts 1, 2, and 3: Apparent oral clearance (CL/F) of PF-07265807

As data permits, single dose (CL/F) and multiple dose pharmacokinetic parameters of PF-07265807

Parts 2 and 3: Apparent clearance (CL/F) of sasanlimab

As data permits, single dose (CL/F) pharmacokinetic parameters of sasanlimab

Time frame: Through study completion, an average of 1 year

Parts 1, 2, and 3: Apparent terminal volume of distribution (Vz/F) of PF-07265807

As data permits, single dose (Vz/F) and multiple dose (Vss/F) pharmacokinetic parameters of PF-07265807

Parts 2 and 3: Apparent terminal volume of distribution (Vz/F) of sasanlimab

As data permits, single dose (Vz/F) pharmacokinetic parameters of sasanlimab

Time frame: Through study completion, an average of 1 year

Parts 1, 2, and 3: ORR

Response will be evaluable via radiographical tumor assessment by RECIST v1.1

Time frame: Baseline through approximately 2 years

Part 4: Number of participants with treatment emergent AEs

AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy

Time frame: Baseline through approximately 2 years

Part 4: Number of participants with laboratory abnormalities

Laboratory abnormalities as characterized by type, frequency, severity, and timing

Time frame: Baseline through approximately 2 years

Part 4: Trough concentration (Ctrough) of PF-07265807 and its metabolite

Predose (Ctrough) pharmacokinetic (PK) parameter of PF-07265807 and its metabolite

Time frame: Each cycle is 21 days. Cycle 1 Days 1 and 14 predose, 2, 4 hours post dose; Cycle 1 Day 7 predose and 2 hours post dose; Cycle 2 Days 1 and 14 predose

Part 4: Post dose concentration (Cmax) of PF-07265807 and its metabolite

Post dose (Cmax) pharmacokinetic (PK) parameter of PF-07265807 and its metabolite

Time frame: Each cycle is 21 days. Cycle 1 Days 1 and 14 predose, 2, 4 hours post dose; Cycle 1 Day 7 predose and 2 hours post dose; Cycle 2 Days 1 and 14 predose

Part 4, Cohorts 2, 3 and 4: Trough concentration (Ctrough) of sasanlimab

Predose (Ctrough) pharmacokinetic (PK) parameter of sasanlimab

Time frame: Each cycle is 21 days. Cycle 1 Days 1, 7, and 14, Cycle 2 Day 1, Cycle 7 Day 1, and every 6 cycles thereafter predose

Part 4, Cohort 4: Trough concentration (Ctrough) of axitinib

Predose (Ctrough) pharmacokinetic (PK) parameter of axitinib

Time frame: Each cycle is 21 days. Cycle 1 Day 1 predose; Cycle 1 Day 14 predose, 2, and 4 hours post dose

Parts 2, 3, and 4 Cohorts 2-4: Immunogenicity of sasanlimab when given in combination

Incidence and titer of anti-sasanlimab ADA response

Time frame: Through study completion, an average of 1 year

Duration of Response

Response will be evaluable via radiographical tumor assessment by RECIST v1.1

Time frame: Baseline through approximately 2 years

Disease Control Rate

Response will be evaluable via radiographical tumor assessment by RECIST v1.1

Time frame: Baseline through approximately 2 years

Progression Free Survival

Response will be evaluable via radiographical tumor assessment by RECIST v1.1

Time frame: Baseline through approximately 2 years