A Study to Learn About the Study Medicine Called PF-07799544 in People With Advanced Solid Tumors
- Conditions
- MelanomaGliomaThyroid CancerNon-Small Cell Lung CancerMalignant NeoplasmsBrain NeoplasmsColorectal Cancer
- Interventions
- Registration Number
- NCT05538130
- Lead Sponsor
- Pfizer
- Brief Summary
The purpose of this clinical trial is to learn the safety and effects of the study medicine (PF-07799544) administered as a single agent and in combination with other study medications in people with solid tumors. This study is seeking participants who have an advanced solid tumor for which the available treatments are no longer effective in controlling their cancer. All participants in this study will receive PF-07799544. PF-07799544 comes as a tablet to take by mouth daily (initially 2 times per day, but this could change to once daily or another frequency). Depending on the part of the study, participants may also receive another study medicine.
* In the first part of the study, people with melanoma or other solid tumors may also receive encorafenib. Encorafenib comes as a capsule and is taken once per day.
* In the second part of the study, people with melanoma or other cancers with abnormalities in a gene called "BRAF" will receive PF-07799544 with other study medicines (for example, PF-07799933).
Participants may receive the study medicines for about 2 years. The study team will monitor how each participant is doing with the study treatment during regular visits at the study clinic.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 124
- Diagnosis of advanced/metastatic solid tumor including primary brain tumor for monotherapy phase 1a dose escalation
- Disease progressed during/following last prior treatment and no satisfactory alternative treatment options for monotherapy phase 1a dose escalation
- For Substudy B, histological or cytological diagnosis of advanced/metastatic melanoma
- For Substudy C, unresectable or adv/metastatic solid tumor progressed on, or with demonstrated intolerance to SOC, excluding melanoma,
- For Substudy B and C, measurable disease by RECIST version 1.1
- For Substudy B, evidence of a BRAF V600 mutation or BRAF Class II/III alteration in tumor tissue and/or blood
- For Substudy C, evidence of a BRAF founder alteration (non-V600 Class II/III BRAF alteration)
- Brain metastasis larger than 4 cm
- History or current evidence of retinal vein occlusion (RVO) or concurrent neuromuscular disorder associated with elevated creatine kinase (CK)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Monotherapy Dose Escalation (Phase 1a) PF-07799544 Participants will receive PF-07799544 Monotherapy Dose Escalation (Phase 1a) encorafenib Participants will receive PF-07799544 Phase 1b Substudy B Combination Dose Escalation PF-07799544 Participants will receive PF-07799544 and PF-07799933 Phase 1b Substudy B Combination Dose Expansion PF-07799544 Participants will receive PF-07799544 and PF-07799933 Phase 1b Substudy C Combination Dose Expansion PF-07799544 Participants will receive PF-07799544 and PF-07799933 Phase 1b Substudy C Combination Dose Expansion PF-07799933 Participants will receive PF-07799544 and PF-07799933 Phase 1b Substudy B Combination Dose Escalation PF-07799933 Participants will receive PF-07799544 and PF-07799933 Phase 1b Substudy B Combination Dose Expansion PF-07799933 Participants will receive PF-07799544 and PF-07799933
- Primary Outcome Measures
Name Time Method Number of participants with dose limiting toxicities (DLTs) Phase 1a monotherapy and Phase 1b combination therapy dose escalation Cycle 1 (21 days) 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)
Overall response rate (ORR) (phase 1b expansion) Baseline to 2 years Response will be evaluated via radiographical tumor assessments by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
Number of participants with clinically significant change from baseline in laboratory abnormalities (phase 1a and phase 1b dose escalation phase) Baseline to 28 days after last dose of study treatment Laboratory abnormalities as characterized by type, frequency, severity, and timing.
Number of participants with treatment-emergent adverse events (AEs) (phase 1a and 1b dose escalation phases) Baseline to 28 days after last dose of study medication AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy
Number of participants with clinically significant change from baseline in vital sign abnormalities (phase 1a and phase 1b dose escalation phase) Baseline to 28 days after last dose of study treatment Vital sign abnormalities as characterized by type, frequency, severity, and timing.
Number of participants with clinically significant change from baseline in physical exam abnormalities (phase 1a and phase 1b dose escalation phase) Baseline to 28 days after last dose of study treatment Physical exam abnormalities as as graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
- Secondary Outcome Measures
Name Time Method PK parameters of PF-07799933, Multiple dose, terminal elimination half life (t½) Baseline to 2 years PK parameters of PF-07799933, Multiple dose, t½
PK parameters of PF-07799933, Multiple dose, apparent oral clearance (CL/F) Baseline to 2 years PK parameters of PF-07799933, Multiple dose, CL/F
Number of participants with treatment-emergent adverse events (AEs) Baseline to 2 years AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy
Number of participants with clinically significant change from baseline in vital sign abnormalities Baseline to 2 years Vital sign abnormalities as characterized by type, frequency, severity, and timing.
PK parameters of PF-07799933, Single dose, terminal elimination half life (t½) Baseline to 2 years PK parameters of PF-07799933, Single dose, t½
PK parameters of PF-07799933, Single dose, apparent oral clearance (CL/F) Baseline to 2 years PK parameters of PF-07799933, Single dose, CL/F
PK parameters of PF-07799933, Single dose, apparent volume of distribution (Vz/F) Baseline to 2 years PK parameters of PF-07799933, Single dose, Vz/F
PK parameters of PF-07799933, Multiple dose, maximum observed concentration (Cmax) Baseline to 2 years PK parameters of PF-07799933, Multiple dose, Cmax
PK parameters of PF-07799933, Multiple dose, time to maximum plasma concentration (Tmax) Baseline to 2 years PK parameters of PF-07799933, Multiple dose, Tmax
PK parameters of PF-07799933, Multiple dose, area under the plasma concentration-time curve over the dosing interval (AUCτ) Baseline to 2 years PK parameters of PF-07799933, Multiple dose, AUCτ
PK parameters of PF-07799933, Multiple dose, apparent volume of distribution (Vz/F) Baseline to 2 years PK parameters of PF-07799933, Multiple dose, Vz/F
ORR (phase 1a and phase 1b dose escalation) Baseline to 2 years ORR as assessed using the RECIST version 1.1.
Duration of response overall and in CNS Baseline to 2 years Intracranial response (phase 1b Part 2) Baseline to 2 years Intracranial response by RECIST version 1.1 (for brain metastases)
PFS Baseline to 2 years PK parameters of PF-07799544, Single dose, time to maximum plasma concentration (Tmax) Baseline to 2 years PK parameters of PF-07799544, Single dose, Tmax
PK parameters of PF-07799544, Single dose, area under the plasma concentration-time curve from time 0 to the last time point of quantifiable concentration (AUClast) Baseline to 2 years PK parameters of PF-07799544, Single dose, AUClast
PK parameters of PF-07799544, Single dose, area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUCinf) Baseline to 2 years PK parameters of PF-07799544, Single dose, AUCinf
PK parameters of PF-07799544, Single dose, terminal elimination half life (t½) Baseline to 2 years PK parameters of PF-07799544, Single dose, t½
PK parameters of PF-07799544, Single dose, apparent oral clearance (CL/F) Baseline to 2 years PK parameters of PF-07799544, Single dose, CL/F
Number of participants with clinically significant change from baseline in laboratory abnormalities Baseline to 2 years Laboratory abnormalities as characterized by type, frequency, severity, and timing.
PK parameters of PF-07799544, Single dose, maximum observed concentration (Cmax) Baseline to 2 years PK parameters of PF-07799544, Single dose, Cmax
PK parameters of PF-07799544, Multiple dose, maximum observed concentration (Cmax) Baseline to 2 years PK parameters of PF-07799544, Multiple dose, Cmax
PK parameters of PF-07799544, Multiple dose, time to maximum plasma concentration (Tmax) Baseline to 2 years PK parameters of PF-07799544, Multiple dose, Tmax
PK parameters of PF-07799544, Multiple dose, area under the plasma concentration-time curve over the dosing interval (AUCτ) Baseline to 2 years PK parameters of PF-07799544, Multiple dose, AUCτ
PK parameters of PF-07799544, Multiple dose, terminal elimination half life (t½) Baseline to 2 years PK parameters of PF-07799544, Multiple dose, t½
PK parameters of PF-07799544, Multiple dose, apparent oral clearance (CL/F) Baseline to 2 years PK parameters of PF-07799544, Multiple dose, CL/F
PK parameters of PF-07799544, Multiple dose, apparent volume of distribution (Vz/F) Baseline to 2 years PK parameters of PF-07799544, Multiple dose, Vz/F
PK parameters of PF-07799933, Single dose, maximum observed concentration (Cmax) Baseline to 2 years PK parameters of PF-07799933, Single dose, Cmax
PK parameters of PF-07799933, Single dose, time to maximum plasma concentration (Tmax) Baseline to 2 years PK parameters of PF-07799933, Single dose, Tmax
PK parameters of PF-07799933, Single dose, area under the plasma concentration-time curve from time 0 to the last time point of quantifiable concentration (AUClast) Baseline to 2 years PK parameters of PF-07799933, Single dose, AUClast
PK parameters of PF-07799933, Single dose, area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUCinf) Baseline to 2 years PK parameters of PF-07799933, Single dose, AUCinf
PK parameters of PF-07799544, Single dose, apparent volume of distribution (Vz/F) Baseline to 2 years PK parameters of PF-07799544, Single dose, Vz/F
Trial Locations
- Locations (39)
Memorial Sloan Kettering Cancer Center 53rd street.
🇺🇸New York, New York, United States
Columbia University Irving Medical Center
🇺🇸New York, New York, United States
Columbia University Medical Center - Neurological Institute of New York
🇺🇸New York, New York, United States
CUIMC Research Pharmacy
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center - Main Campus
🇺🇸New York, New York, United States
MSK Nassau.
🇺🇸Uniondale, New York, United States
Cleveland Clinic Taussig Cancer Center Investigational Pharmacy
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic Taussig Cancer Center
🇺🇸Cleveland, Ohio, United States
Providence Cancer Institute Franz Clinic
🇺🇸Portland, Oregon, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Sarah Cannon Research Institute- Pharmacy
🇺🇸Nashville, Tennessee, United States
SCRI Oncology Partners
🇺🇸Nashville, Tennessee, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
The Ottawa Hospital - General Campus
🇨🇦Ottawa, Ontario, Canada
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
McGill University Health Centre
🇨🇦Montréal, Quebec, Canada
Sunnybrook Research Institute
🇨🇦Toronto, Ontario, Canada
Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus
🇨🇦Quebec City, Quebec, Canada
Soroka Medical Center
🇮🇱Beer-Sheva, Hadarom, Israel
Rabin Medical Center
🇮🇱Petah Tikva, Hamerkaz, Israel
Sheba Medical Center
🇮🇱Ramat Gan, Hamerkaz, Israel
Sourasky Medical Center
🇮🇱Tel Aviv, Tell Abīb, Israel
Hadassah Medical Center
🇮🇱Jerusalem, Yerushalayim, Israel
Highlands Oncology Group
🇺🇸Rogers, Arkansas, United States
Highlands Oncology Group, PA
🇺🇸Springdale, Arkansas, United States
Moffitt Cancer Center, Richard M. Shulze Family Foundation Outpatient Center
🇺🇸Tampa, Florida, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Moffitt McKinley Hospital
🇺🇸Tampa, Florida, United States
Brigitte Harris Cancer Pavilion
🇺🇸Detroit, Michigan, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
MSK Basking Ridge.
🇺🇸Basking Ridge, New Jersey, United States
MSK Monmouth.
🇺🇸Middletown, New Jersey, United States
MSK Bergen.
🇺🇸Montvale, New Jersey, United States
MSK Commack.
🇺🇸Commack, New York, United States
MSK Westchester.
🇺🇸Harrison, New York, United States