A PHASE 1A/B OPEN-LABEL MASTER STUDY OF PF-07799544 AS A SINGLE-AGENT AND IN COMBINATION WITH OTHER TARGETED AGENTS IN PARTICIPANTS WITH BRAF-MUTANT MELANOMA AND OTHER SOLID TUMORS
Summary
The purpose of this clinical trial is to learn the safety and effects of the study medicine (PF-07799544) alone or in combination as a potential cancer treatment for adults with advanced solid tumors. The study will be conducted in two parts: PF-07799544 as a single agent (Phase 1a) and PF-07799544 in combination with another study medicine called PF-07799933 (Phase 1b). Phase 1a is no longer open for enrollment. In Phase1b (noted as "this study"), we are seeking participants who have: * a solid tumor which is metastatic or recurrent (excluding colorectal cancer) * tumor with the mutation (abnormal gene) called "BRAF V600" * received required prior treatment for cancer per cohort assigned. All participants in this study will receive both study medicines. Both study medicines are tablets that are taken by mouth at home twice a day. Participants will receive study medicines until their cancer is no longer responding, unacceptable side effects, or 2 years. Participants may continue to receive study therapy beyond 2 years. We will examine the experiences of people receiving the study medicines. This will help us determine if the study medicines are safe and effective.
Arms & interventions
- DrugPF-07799544
Tablet
- DrugPF-07799933
Tablet
Outcome measures
Primary
Phase 1a monotherapy and Phase 1b combination dose escalation: Number of participants with dose limiting toxicities (DLTs)
DLTs will be evaluated during the first cycle (21 days) as a single agent (phase 1a monotherapy) or in combination with other agents (phase 1b dose escalation)
Time frame: Cycle 1 (21 days)
Phase 1a monotherapy and Phase 1b combination dose escalation: 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 to 28 days after last dose of study medication
Phase 1a monotherapy and Phase 1b combination dose escalation: Number of participants with clinically significant change from baseline in laboratory abnormalities
Laboratory abnormalities as characterized by type, frequency, severity, and timing.
Time frame: Baseline to 28 days after last dose of study treatment
Phase 1a monotherapy and Phase 1b combination dose escalation: Number of participants with clinically significant change from baseline in vital sign abnormalities
Vital sign abnormalities as characterized by type, frequency, severity, and timing.
Time frame: Baseline to 28 days after last dose of study treatment
Phase 1a monotherapy and Phase 1b combination dose escalation: Number of participants with clinically significant change from baseline in physical exam abnormalities
Physical exam abnormalities as as graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Time frame: Baseline to 28 days after last dose of study treatment
Phase 1b Dose Expansion: Overall response rate (ORR)
Response will be evaluated via radiographical tumor assessments by RECIST v1.1 for solid tumors or RANO for primary brain tumors
Time frame: Baseline to 2 years
Secondary
Phase 1a monotherapy and Phase 1b combination dose escalation: ORR
Time frame: Baseline to 2 years
Phase 1b Dose Expansion: Number of participants with treatment-emergent adverse events (AEs)
Time frame: Baseline to 2 years
Phase 1b Dose Expansion: Number of participants with clinically significant change from baseline in vital sign abnormalities
Time frame: Baseline to 2 years
Phase 1b Dose Expansion: Number of participants with clinically significant change from baseline in laboratory abnormalities
Time frame: Baseline to 2 years
Phase 1b Dose Expansion: Duration of Response (Overall and in CNS)
Time frame: Baseline to 2 years
Phase 1b Dose Expansion: Intracranial response
Time frame: Baseline to 2 years
Phase 1b Dose Expansion: Progression Free Survival (PFS)
Time frame: Baseline to 2 years
PK Parameters: Maximum Observed Concentration (Cmax)
Time frame: Baseline to 2 years
PK Parameters: Maximum Plasma Concentration (Tmax)
Time frame: Baseline to 2 years
PK Parameters: Area Under Curve (AUC)
Time frame: Baseline to 2 years
PK Parameters: terminal elimination half-life (t½)
Time frame: Baseline to 2 years
PK Parameters: Apparent Oral Clearance (CL/F)
Time frame: Baseline to 2 years
PK Parameters: Apparent Volume of Distribution (Vz/F)
Time frame: Baseline to 2 years
Eligibility criteria
Study locations (58)
The Kirklin Clinic of UAB Hospital
Birmingham, Alabama, 35233
The University of Alabama at Birmingham
Birmingham, Alabama, 35249
University of Alabama at Birmingham - Phase I Clinical Trials Unit
Birmingham, Alabama, 35249
Highlands Oncology Group, PA
Fayetteville, Arkansas, 72703
Highlands Oncology Group, PA
Rogers, Arkansas, 72758
Highlands Oncology Group, PA
Springdale, Arkansas, 72762
The Angeles Clinic and Research Institute- A Cedars-Sinai Affiliate
Los Angeles, California, 90025
Keck Hospital of USC
Los Angeles, California, 90033
Los Angeles General Medical Center
Los Angeles, California, 90033
USC/Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Keck Medical Center of USC Pasadena
Pasadena, California, 91105
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94143
UCSF Helen Diller Medical Center at Parnassus Heights
San Francisco, California, 94143
UCSF Medical Center, Investigational Pharmacy
San Francisco, California, 94158
The Angeles Clinic and Research Institue, A Cedars-Sinai Affiliate (Emergency Back-up only)
Santa Monica, California, 90404
Moffitt Cancer Center, Richard M. Shulze Family Foundation Outpatient Center
Tampa, Florida, 33612
Moffitt Cancer Center
Tampa, Florida, 33612
Moffitt McKinley Hospital
Tampa, Florida, 33612
Ochsner Clinic Foundation
New Orleans, Louisiana, 70121
Massachusetts General Hospital
Boston, Massachusetts, 02114
Ophthalmic Consultants of Boston Inc (OCB)
Boston, Massachusetts, 02114
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Mass General Waltham
Waltham, Massachusetts, 02451
Brigitte Harris Cancer Pavilion
Detroit, Michigan, 48202
Henry Ford Hospital
Detroit, Michigan, 48202
HealthPartners Frauenshuh Cancer Center
Saint Louis Park, Minnesota, 55426
Methodist Hospital Inpatient Pharmacy
Saint Louis Park, Minnesota, 55426
HealthPartners Cancer Center at regions Hospital
Saint Paul, Minnesota, 55101
Regions Hospital Pharmacy
Saint Paul, Minnesota, 55101
MSK Basking Ridge.
Basking Ridge, New Jersey, 07920
MSK Monmouth.
Middletown, New Jersey, 07748
MSK Bergen.
Montvale, New Jersey, 07645
Optum Medical Care, PC
Brewster, New York, 10509
MSK Commack.
Commack, New York, 11725
MSK Westchester.
Harrison, New York, 10604
Optum Medical Care, PC
Mount Kisco, New York, 10549
Laura & Isaac Perlmutter Cancer Center - NYU ACC
New York, New York, 10016
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
New York, New York, 10016
NYU Langone Faculty Group Practice
New York, New York, 10016
NYU Langone Medical Center (Tisch Hospital)
New York, New York, 10016
Memorial Sloan Kettering Cancer Center 53rd street.
New York, New York, 10022
Columbia University Irving Medical Center
New York, New York, 10032
Columbia University Medical Center - Neurological Institute of New York
New York, New York, 10032
CUIMC Research Pharmacy
New York, New York, 10032
Memorial Sloan Kettering Cancer Center - Main Campus
New York, New York, 10065
MSK Nassau.
Uniondale, New York, 11553
Cleveland Clinic Taussig Cancer Center Investigational Pharmacy
Cleveland, Ohio, 44106
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, 44195
Providence Cancer Institute Franz Clinic
Portland, Oregon, 97213
Providence Portland Medical Center
Portland, Oregon, 97213
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
SCRI Oncology Partners
Nashville, Tennessee, 37203
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
University of Washington Medical Center
Seattle, Washington, 98195
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin, 53718
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792