Study of PF-07265807 in Participants With Metastatic Solid Tumors.
- Conditions
- Neoplasm Metastasis
- Interventions
- Registration Number
- NCT04458259
- Lead Sponsor
- Pfizer
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 67
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Monotherapy Dose Escalation: Part 1 PF-07265807 Monotherapy dose escalation of PF-07265807 in participants with select tumor types. Triplet Dose Escalation: Part 3 Sasanlimab Triplet combination dose escalation of PF-07265807 with sasanlimab plus axitinib in participants with select tumor types. PF-07265807 will dose escalate. Sasanlimab dose will stay constant. Axitinib dose will follow label. Expansion Phase: Part 4, Cohort 1 PF-07265807 PF-07265807 monotherapy in participants with METex14 mutant NSCLC. Triplet Dose Escalation: Part 3 Axitinib Triplet combination dose escalation of PF-07265807 with sasanlimab plus axitinib in participants with select tumor types. PF-07265807 will dose escalate. Sasanlimab dose will stay constant. Axitinib dose will follow label. Expansion Phase: Part 4, Cohort 2 PF-07265807 PF-07265807 with sasanlimab in participants with MSS CRC Expansion Phase: Part 4, Cohort 2 Sasanlimab PF-07265807 with sasanlimab in participants with MSS CRC Expansion Phase: Part 4, Cohort 3 Sasanlimab PF-07265807 with sasanlimab in participants with PD-L1+ gastric cancer/GEJ Doublet Dose Escalation: Part 2 Sasanlimab Doublet combination dose escalation of PF-07265807 with sasanlimab in participants with select tumor types. PF-07265807 will dose escalate. Sasanlimab dose will stay constant. Doublet Dose Escalation: Part 2 PF-07265807 Doublet combination dose escalation of PF-07265807 with sasanlimab in participants with select tumor types. PF-07265807 will dose escalate. Sasanlimab dose will stay constant. Triplet Dose Escalation: Part 3 PF-07265807 Triplet combination dose escalation of PF-07265807 with sasanlimab plus axitinib in participants with select tumor types. PF-07265807 will dose escalate. Sasanlimab dose will stay constant. Axitinib dose will follow label. Expansion Phase: Part 4, Cohort 3 PF-07265807 PF-07265807 with sasanlimab in participants with PD-L1+ gastric cancer/GEJ Expansion Phase: Part 4, Cohort 4 PF-07265807 PF-07265807 with sasanlimab plus axitinib in participants with RCC Expansion Phase: Part 4, Cohort 4 Sasanlimab PF-07265807 with sasanlimab plus axitinib in participants with RCC Expansion Phase: Part 4, Cohort 4 Axitinib PF-07265807 with sasanlimab plus axitinib in participants with RCC
- Primary Outcome Measures
Name Time Method Parts 1, 2, and 3: Number of participants with dose limiting toxicities (DLTs) Baseline through day 21 or 42 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)
Parts 1, 2, and 3: Number of participants with laboratory abnormalities Baseline through approximately 2 years Laboratory abnormalities as characterized by type, frequency, severity, and timing.
Part 4, Cohort 4: Complete Response (CR) Baseline through approximately 2 years Response will be evaluated via radiographical tumor assessment by RECIST v1.1
Parts 1, 2 and 3: Number of participants with treatment emergent adverse events (AEs) Baseline through approximately 2 years AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy
Part 4: Overall Response Rate (ORR) Baseline through approximately 2 years Response will be evaluable via radiographical tumor assessment by RECIST v1.1
- Secondary Outcome Measures
Name Time Method Part 3: Maximum plasma concentration at steady state (Cmax,ss) 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 Multiple dose (assuming steady state is achieved; Cmax,ss) pharmacokinetic (PK) parameters of axitinib
Parts 1, 2, and 3: Time to reach maximum plasma concentration (Tmax) 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 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: Area under the curve from the time of dose to the last measurable concentration (AUClast) of sasanlimab Through study completion, an average of 1 year Single dose (AUClast) pharmacokinetic parameters of sasanlimab
Parts 2 and 3: Maximum plasma concentration (Cmax) of sasanlimab Through study completion, an average of 1 year Single dose (Cmax) pharmacokinetic (PK) parameters of sasanlimab
Parts 2 and 3: Time to reach maximum plasma concentration (Tmax) of sasanlimab Through study completion, an average of 1 year Single dose (Tmax) pharmacokinetic parameters of sasanlimab
Part 3: Time to reach maximum plasma concentration at steady state (Tmax,ss) 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 Multiple dose (assuming steady state is achieved; Tmax,ss) pharmacokinetic parameters of axitinib
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 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 Single dose (AUClast) pharmacokinetic parameters of PF-07265807 and its metabolite
Parts 2 and 3: Apparent clearance (CL/F) of sasanlimab Through study completion, an average of 1 year As data permits, single dose (CL/F) pharmacokinetic parameters of sasanlimab
Parts 1, 2, and 3: Apparent terminal volume of distribution (Vz/F) 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 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 Through study completion, an average of 1 year As data permits, single dose (Vz/F) pharmacokinetic parameters of sasanlimab
Parts 1, 2, and 3: ORR Baseline through approximately 2 years Response will be evaluable via radiographical tumor assessment by RECIST v1.1
Part 4: Number of participants with treatment emergent AEs Baseline through approximately 2 years AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy
Part 4: Number of participants with laboratory abnormalities Baseline through approximately 2 years Laboratory abnormalities as characterized by type, frequency, severity, and timing
Part 4: Trough concentration (Ctrough) 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 Predose (Ctrough) pharmacokinetic (PK) parameter of PF-07265807 and its metabolite
Part 4: Post dose concentration (Cmax) 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 Post dose (Cmax) pharmacokinetic (PK) parameter of PF-07265807 and its metabolite
Parts 1, 2, and 3: Maximum plasma concentration (Cmax) 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 Single dose (Cmax) and multiple dose (assuming steady state is achieved; Cmax,ss) pharmacokinetic (PK) 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 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 Multiple dose assuming steady state is achieved (AUCtau,ss) pharmacokinetic parameters of axitinib
Parts 1, 2, and 3: Terminal elimination half-life (t1/2) 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 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 Through study completion, an average of 1 year As data permits, single dose (t1/2) pharmacokinetic parameters of sasanlimab
Parts 1, 2, and 3: Area under the curve from the time of dose extrapolated to infinity (AUCinf) 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 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 Through study completion, an average of 1 year As data permits, single dose (AUCinf) pharmacokinetic parameters of sasanlimab
Parts 1, 2, and 3: Apparent oral clearance (CL/F) 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 As data permits, single dose (CL/F) and multiple dose pharmacokinetic parameters of PF-07265807
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 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 Multiple dose assuming steady state is achieved (AUCtau,ss) pharmacokinetic parameters of PF-07265807 and its metabolite
Parts 2, 3, and 4 Cohorts 2-4: Immunogenicity of sasanlimab when given in combination Through study completion, an average of 1 year Incidence and titer of anti-sasanlimab ADA response
Duration of Response Baseline through approximately 2 years Response will be evaluable via radiographical tumor assessment by RECIST v1.1
Part 4, Cohorts 2, 3 and 4: Trough concentration (Ctrough) 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 Predose (Ctrough) pharmacokinetic (PK) parameter of sasanlimab
Part 4, Cohort 4: Trough concentration (Ctrough) of axitinib Each cycle is 21 days. Cycle 1 Day 1 predose; Cycle 1 Day 14 predose, 2, and 4 hours post dose Predose (Ctrough) pharmacokinetic (PK) parameter of axitinib
Progression Free Survival Baseline through approximately 2 years Response will be evaluable via radiographical tumor assessment by RECIST v1.1
Disease Control Rate Baseline through approximately 2 years Response will be evaluable via radiographical tumor assessment by RECIST v1.1
Trial Locations
- Locations (55)
Community Health Network Cancer Center North
🇺🇸Indianapolis, Indiana, United States
Community Health Network Investigational Drug Services
🇺🇸Indianapolis, Indiana, United States
Rocky Mountain Lions Eye Institute (RMLEI)
🇺🇸Aurora, Colorado, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
Brigham & Women's Hospital
🇺🇸Boston, Massachusetts, United States
John Theurer Cancer Center at Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Community Health Network, Inc.
🇺🇸Indianapolis, Indiana, United States
Hospital Universitario Fundacion Jimenez DÃaz
🇪🇸Madrid, Spain
CHU de Quebec-Universite Laval - Hotel Dieu de Quebec
🇨🇦Québec, Quebec, Canada
Calvary Mater Newcastle
🇦🇺Waratah, New South Wales, Australia
Fondazione IRCCS San Gerardo dei Tintori
🇮🇹Monza, Lombardia, Italy
Hospital Universitario HM Sanchinarro
🇪🇸Madrid, Spain
The University of Texas M. D. Anderson Cancer Center
🇺🇸Houston, Texas, United States
St Vincent's Hospital
🇦🇺Sydney, New South Wales, Australia
Hamilton Health Sciences-Juravinski Cancer Centre
🇨🇦Hamilton, Ontario, Canada
University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)
🇺🇸Aurora, Colorado, United States
Dana-Farber Cancer Institute - Chestnut Hill
🇺🇸Newton, Massachusetts, United States
University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)
🇺🇸Aurora, Colorado, United States
Azienda Ospedaliero Universitaria delle Marche
🇮🇹Ancona, AN, Italy
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
National Cancer Center Hospital East
🇯🇵Kashiwa, Chiba, Japan
University Health Network
🇨🇦Toronto, Ontario, Canada
Chayagasaka Eye Clinic
🇯🇵Nagoya, Aichi, Japan
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Aichi Cancer Center Hospital
🇯🇵Nagoya, Nagoya, Aichi, Japan
Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore
🇮🇹Roma, Italy
Severance Hospital
🇰🇷Seoul, Korea, Republic of
Istituto Nazionale Tumori IRCCS Fondazione Giovanni Pascale
🇮🇹Napoli, Italy
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Seoul-teukbyeolsi [seoul], Korea, Republic of
Istituto Europeo di Oncologia IRCCS
🇮🇹Milano, Italy
Asan Medical Center
🇰🇷Songpa-gu, Seoul-teukbyeolsi [seoul], Korea, Republic of
Duke Eye Center
🇺🇸Durham, North Carolina, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, 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
UC Irvine Health
🇺🇸Orange, California, United States
Highlands Oncology Group
🇺🇸Springdale, Arkansas, United States
UC Irvine Medical Center
🇺🇸Orange, California, United States
Henry Eye Clinic
🇺🇸Fayetteville, Arkansas, United States
UCI/Chao Family Comprehensive Cancer Center
🇺🇸Orange, California, United States
UCI Chao Family Comprehensive Cancer Center
🇺🇸Orange, California, United States
UCI Medical Center- Outpatient Pharmacy
🇺🇸Orange, California, United States
University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)
🇺🇸Aurora, Colorado, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
HPS Pharmacies Darlinghurst
🇦🇺Darlinghurst, New South Wales, Australia
Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus
🇨🇦Quebec City, Quebec, Canada
Macquarie University
🇦🇺Macquarie University, New South Wales, Australia
Guangdong Provincial People's Hospital
🇨🇳Guangzhou, Guangdong, China
Jilin Province Tumor Hospital
🇨🇳Changchun, Jilin, China