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

Neoplasm Metastasis Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04458259
• Other study ID #: C4201002
• Secondary ID: ARRAY-067-102202
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: September 24, 2020
• Est. completion date: June 30, 2024

Study information

• Verified date: April 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 67
• Est. completion date: June 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Neoplasm Metastasis

Intervention

Drug:
• PF-07265807
Given 2 weeks on/1 week off
• Sasanlimab
Given SC Q3W
• Axitinib
Dosed per package label starting with 5 mg PO BID

Locations

Country	Name	City	State
Australia	HPS Pharmacies Darlinghurst	Darlinghurst	New South Wales
Australia	Macquarie University	Macquarie University	New South Wales
Australia	St Vincent's Hospital	Sydney	New South Wales
Australia	Calvary Mater Newcastle	Waratah	New South Wales
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Hamilton Health Sciences-Juravinski Cancer Centre	Hamilton	Ontario
Canada	CHU de Quebec-Universite Laval - Hotel Dieu de Quebec	Québec	Quebec
Canada	Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus	Quebec City	Quebec
Canada	University Health Network	Toronto	Ontario
China	Jilin Province Tumor Hospital	Changchun	Jilin
China	Guangdong Provincial People's Hospital	Guangzhou	Guangdong
Italy	Azienda Ospedaliero Universitaria delle Marche	Ancona	AN
Italy	Istituto Europeo di Oncologia IRCCS	Milano
Italy	Fondazione IRCCS San Gerardo dei Tintori	Monza	Lombardia
Italy	Istituto Nazionale Tumori IRCCS Fondazione Giovanni Pascale	Napoli
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore	Roma
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore	Roma	Rome
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	Aichi Cancer Center Hospital	Nagoya	Nagoya, Aichi
Japan	Chayagasaka Eye Clinic	Nagoya	Aichi
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do
Korea, Republic of	Seoul National University Hospital	Seoul	Seoul-teukbyeolsi [seoul]
Korea, Republic of	Severance Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	Asan Medical Center	Songpa-gu	Seoul-teukbyeolsi [seoul]
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario Fundacion Jimenez Díaz	Madrid
Spain	Hospital Universitario HM Sanchinarro	Madrid
Spain	Hospital Clinico Universitario de Valencia	Valencia
United States	Rocky Mountain Lions Eye Institute (RMLEI)	Aurora	Colorado
United States	University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)	Aurora	Colorado
United States	University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)	Aurora	Colorado
United States	University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)	Aurora	Colorado
United States	Brigham & Women's Hospital	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Duke Eye Center	Durham	North Carolina
United States	Duke University Medical Center	Durham	North Carolina
United States	Henry Eye Clinic	Fayetteville	Arkansas
United States	Highlands Oncology Group	Fayetteville	Arkansas
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	The University of Texas M. D. Anderson Cancer Center	Houston	Texas
United States	Community Health Network Cancer Center North	Indianapolis	Indiana
United States	Community Health Network Investigational Drug Services	Indianapolis	Indiana
United States	Community Health Network, Inc.	Indianapolis	Indiana
United States	Community Health Network, Inc.	Indianapolis	Indiana
United States	Community Health Network, Inc.	Indianapolis	Indiana
United States	Community Health Network, Inc.	Indianapolis	Indiana
United States	Dana-Farber Cancer Institute - Chestnut Hill	Newton	Massachusetts
United States	UC Irvine Health	Orange	California
United States	UC Irvine Health	Orange	California
United States	UC Irvine Medical Center	Orange	California
United States	UCI Chao Family Comprehensive Cancer Center	Orange	California
United States	UCI Medical Center- Outpatient Pharmacy	Orange	California
United States	UCI/Chao Family Comprehensive Cancer Center	Orange	California
United States	Highlands Oncology Group	Rogers	Arkansas
United States	Clinical & Translational Science Institute	San Francisco	California
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	UCSF Helen Diller Family Comprehensive Cancer Center - Mission Hall	San Francisco	California
United States	UCSF Investigational Drugs Pharmacy	San Francisco	California
United States	Highlands Oncology Group	Springdale	Arkansas

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Australia,  Canada,  China,  Italy,  Japan,  Korea, Republic of,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Baseline through day 21 or 42
Primary	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	Baseline through approximately 2 years
Primary	Parts 1, 2, and 3: Number of participants with laboratory abnormalities	Laboratory abnormalities as characterized by type, frequency, severity, and timing.	Baseline through approximately 2 years
Primary	Part 4: Overall Response Rate (ORR)	Response will be evaluable via radiographical tumor assessment by RECIST v1.1	Baseline through approximately 2 years
Primary	Part 4, Cohort 4: Complete Response (CR)	Response will be evaluated via radiographical tumor assessment by RECIST v1.1	Baseline through approximately 2 years
Secondary	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	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
Secondary	Parts 2 and 3: Maximum plasma concentration (Cmax) of sasanlimab	Single dose (Cmax) pharmacokinetic (PK) parameters of sasanlimab	Through study completion, an average of 1 year
Secondary	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	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
Secondary	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	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
Secondary	Parts 2 and 3: Time to reach maximum plasma concentration (Tmax) of sasanlimab	Single dose (Tmax) pharmacokinetic parameters of sasanlimab	Through study completion, an average of 1 year
Secondary	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	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
Secondary	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	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
Secondary	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	Through study completion, an average of 1 year
Secondary	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	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
Secondary	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	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
Secondary	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	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
Secondary	Parts 2 and 3: Terminal elimination half-life (t1/2) of sasanlimab	As data permits, single dose (t1/2) pharmacokinetic parameters of sasanlimab	Through study completion, an average of 1 year
Secondary	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	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
Secondary	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	Through study completion, an average of 1 year
Secondary	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	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
Secondary	Parts 2 and 3: Apparent clearance (CL/F) of sasanlimab	As data permits, single dose (CL/F) pharmacokinetic parameters of sasanlimab	Through study completion, an average of 1 year
Secondary	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	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
Secondary	Parts 2 and 3: Apparent terminal volume of distribution (Vz/F) of sasanlimab	As data permits, single dose (Vz/F) pharmacokinetic parameters of sasanlimab	Through study completion, an average of 1 year
Secondary	Parts 1, 2, and 3: ORR	Response will be evaluable via radiographical tumor assessment by RECIST v1.1	Baseline through approximately 2 years
Secondary	Part 4: Number of participants with treatment emergent AEs	AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy	Baseline through approximately 2 years
Secondary	Part 4: Number of participants with laboratory abnormalities	Laboratory abnormalities as characterized by type, frequency, severity, and timing	Baseline through approximately 2 years
Secondary	Part 4: Trough concentration (Ctrough) of PF-07265807 and its metabolite	Predose (Ctrough) pharmacokinetic (PK) parameter of PF-07265807 and its metabolite	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
Secondary	Part 4: Post dose concentration (Cmax) of PF-07265807 and its metabolite	Post dose (Cmax) pharmacokinetic (PK) parameter of PF-07265807 and its metabolite	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
Secondary	Part 4, Cohorts 2, 3 and 4: Trough concentration (Ctrough) of sasanlimab	Predose (Ctrough) pharmacokinetic (PK) parameter of sasanlimab	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
Secondary	Part 4, Cohort 4: Trough concentration (Ctrough) of axitinib	Predose (Ctrough) pharmacokinetic (PK) parameter of axitinib	Each cycle is 21 days. Cycle 1 Day 1 predose; Cycle 1 Day 14 predose, 2, and 4 hours post dose
Secondary	Parts 2, 3, and 4 Cohorts 2-4: Immunogenicity of sasanlimab when given in combination	Incidence and titer of anti-sasanlimab ADA response	Through study completion, an average of 1 year
Secondary	Duration of Response	Response will be evaluable via radiographical tumor assessment by RECIST v1.1	Baseline through approximately 2 years
Secondary	Disease Control Rate	Response will be evaluable via radiographical tumor assessment by RECIST v1.1	Baseline through approximately 2 years
Secondary	Progression Free Survival	Response will be evaluable via radiographical tumor assessment by RECIST v1.1	Baseline through approximately 2 years

External Links

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