Clinical trial NCT04458259: Study of PF-07265807 in Participants With Metastatic Solid Tumors.
Official title: A PHASE 1, OPEN-LABEL, MULTI-CENTER, DOSE-FINDING, PHARMACOKINETIC, SAFETY AND TOLERABILITY STUDY OF PF 07265807 IN PARTICIPANTS WITH SELECTED ADVANCED OR METASTATIC SOLID TUMOR MALIGNANCIES
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Neoplasm Metastasis
Keywords: TAMK (TAM kinase)
MER (mer proto-oncogene)
MERTK (mer proto-oncogene tyrosine kinase)
AXL (AXL receptor tyrosine kinase)
AXL/MER
Selective kinase inhibitor
PD-1 (programmed cell death protein 1)
PD-L1 (programmed cell death ligand 1)
Immune modulator
Advanced Cancer
Metastatic Cancer
Solid Tumor Cancer
Metastatic Solid Tumor
Cervical Cancer
Gastric Cancer
Esophageal Cancer
Endometrial Cancer
Hepatocellular carcinoma (HCC)
Melanoma
Merkel Cell Carcinoma
High levels of MicroSatellite Instability deficient MisMatch Repair (MSI-H-dMMR) tumor
Non-small cell lung cancer (NSCLC)
Small cell lung cancer (SCLC)
Renal cell carcinoma (RCC)
Urothelial carcinoma
Colorectal cancer (CRC)
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2020-07-07
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Dose escalation and expansion
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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.

Primary outcomes:
measure: Parts 1, 2, and 3: Number of participants with dose limiting toxicities (DLTs)
timeFrame: Baseline through day 21 or 42
measure: Parts 1, 2 and 3: Number of participants with treatment emergent adverse events (AEs)
timeFrame: Baseline through approximately 2 years
measure: Parts 1, 2, and 3: Number of participants with laboratory abnormalities
timeFrame: Baseline through approximately 2 years
measure: Part 4: Overall Response Rate (ORR)
timeFrame: Baseline through approximately 2 years
measure: Part 4, Cohort 4: Complete Response (CR)
timeFrame: Baseline through approximately 2 years
Secondary outcomes:
measure: Parts 1, 2, and 3: Maximum plasma concentration (Cmax) of PF-07265807 and its metabolite
timeFrame: 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
measure: Parts 2 and 3: Maximum plasma concentration (Cmax) of sasanlimab
timeFrame: Through study completion, an average of 1 year
measure: Part 3: Maximum plasma concentration at steady state (Cmax,ss) of axitinib
timeFrame: 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
measure: Parts 1, 2, and 3: Time to reach maximum plasma concentration (Tmax) of PF-07265807 and its metabolite
timeFrame: 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
measure: Parts 2 and 3: Time to reach maximum plasma concentration (Tmax) of sasanlimab
timeFrame: Through study completion, an average of 1 year
measure: Part 3: Time to reach maximum plasma concentration at steady state (Tmax,ss) of axitinib
timeFrame: 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
measure: 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
timeFrame: 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
measure: Parts 2 and 3: Area under the curve from the time of dose to the last measurable concentration (AUClast) of sasanlimab
timeFrame: Through study completion, an average of 1 year
measure: 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
timeFrame: 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
measure: Part 3: Area under the curve from the time of dose to the time of the subsequent dose (AUCtau) at steady state of axitinib
timeFrame: 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
measure: Parts 1, 2, and 3: Terminal elimination half-life (t1/2) of PF-07265807 and its metabolite
timeFrame: 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
measure: Parts 2 and 3: Terminal elimination half-life (t1/2) of sasanlimab
timeFrame: Through study completion, an average of 1 year
measure: Parts 1, 2, and 3: Area under the curve from the time of dose extrapolated to infinity (AUCinf) of PF-07265807 and its metabolite
timeFrame: 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
measure: Parts 2 and 3: Area under the curve from the time of dose extrapolated to infinity (AUCinf) of sasanlimab
timeFrame: Through study completion, an average of 1 year
measure: Parts 1, 2, and 3: Apparent oral clearance (CL/F) of PF-07265807
timeFrame: 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
measure: Parts 2 and 3: Apparent clearance (CL/F) of sasanlimab
timeFrame: Through study completion, an average of 1 year
measure: Parts 1, 2, and 3: Apparent terminal volume of distribution (Vz/F) of PF-07265807
timeFrame: 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
measure: Parts 2 and 3: Apparent terminal volume of distribution (Vz/F) of sasanlimab
timeFrame: Through study completion, an average of 1 year
measure: Parts 1, 2, and 3: ORR
timeFrame: Baseline through approximately 2 years
measure: Part 4: Number of participants with treatment emergent AEs
timeFrame: Baseline through approximately 2 years
measure: Part 4: Number of participants with laboratory abnormalities
timeFrame: Baseline through approximately 2 years
measure: Part 4: Trough concentration (Ctrough) of PF-07265807 and its metabolite
timeFrame: 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
measure: Part 4: Post dose concentration (Cmax) of PF-07265807 and its metabolite
timeFrame: 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
measure: Part 4, Cohorts 2, 3 and 4: Trough concentration (Ctrough) of sasanlimab
timeFrame: 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
measure: Part 4, Cohort 4: Trough concentration (Ctrough) of axitinib
timeFrame: Each cycle is 21 days. Cycle 1 Day 1 predose; Cycle 1 Day 14 predose, 2, and 4 hours post dose
measure: Parts 2, 3, and 4 Cohorts 2-4: Immunogenicity of sasanlimab when given in combination
timeFrame: Through study completion, an average of 1 year
measure: Duration of Response
timeFrame: Baseline through approximately 2 years
measure: Disease Control Rate
timeFrame: Baseline through approximately 2 years
measure: Progression Free Survival
timeFrame: Baseline through approximately 2 years
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Henry Eye Clinic
state: Arkansas
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Rogers
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Springdale
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Orange
country: United States
facility: UCI Chao Family Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: Clinical & Translational Science Institute
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center - Mission Hall
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: Rocky Mountain Lions Eye Institute (RMLEI)
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)
state: Colorado
city: Indianapolis
country: United States
facility: Community Health Network, Inc.
state: Indiana
city: Indianapolis
country: United States
facility: Community Health Network, Inc.
state: Indiana
city: Indianapolis
country: United States
facility: Community Health Network Cancer Center North
state: Indiana
city: Indianapolis
country: United States
facility: Community Health Network, Inc.
state: Indiana
city: Indianapolis
country: United States
facility: Community Health Network, Inc.
state: Indiana
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Newton
country: United States
facility: Dana-Farber Cancer Institute - Chestnut Hill
state: Massachusetts
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center
state: New Jersey
city: Durham
country: United States
facility: Duke Eye Center
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center, lnvestigational Chemotherapy Service
state: North Carolina
city: Houston
country: United States
facility: The University of Texas M. D. Anderson Cancer Center
state: Texas
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore
state: Rome
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione Giovanni Pascale
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: