A Study to Learn About the Study Medicine Called PF-07799544 in People With Advanced Solid Tumors

Study Overview
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Brief Summary
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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 with a certain type of abnormal gene called BRAF will receive PF-07799544 with other study medicines (for example, PF-07284890 or 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.

Official Title
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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 ADVANCED SOLID TUMORS

Conditions
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Melanoma, Glioma, Thyroid Cancer, Non-Small Cell Lung Cancer, Malignant Neoplasms, Brain Neoplasms, Colorectal Cancer

Intervention / Treatment
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* Drug: PF-07799544
* Drug: PF-07284890
* Drug: PF-07799933
* Drug: encorafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 A and B, histological or cytological diagnosis of advanced/metastatic melanoma For Substudy A and B, measurable disease by RECIST version 1.1 For Substudy A, evidence of a BRAF V600 mutation in tumor tissue and/or blood For Substudy B, evidence of a BRAF V600 mutation or BRAF Class II alteration in tumor tissue and/or blood Exclusion Criteria: Brain metastasis larger than 4 cm Systemic anti-cancer therapy or small molecule therapeutics ongoing at the start of study treatment. For participants who may get binimetinib on study, history or current evidence of retinal vein occlusion (RVO) or concurrent neuromuscular disorder associated with elevated creatine kinase (CK)

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Monotherapy Dose Escalation (Phase 1a)<br>Participants will receive PF-07799544 | Drug: PF-07799544<br>* Tablet<br>* Other names: ARRY-134;Drug: encorafenib<br>* Capsule<br>* Other names: BRAFTOVI;|
| Experimental: Phase 1b Substudy A Combination Dose Escalation<br>Participants will receive PF-07799544 and PF-07284890 | Drug: PF-07799544<br>* Tablet<br>* Other names: ARRY-134;Drug: PF-07284890<br>* Tablet<br>* Other names: ARRY-461;|
| Experimental: Phase 1b Substudy A Dose Expansion Cohort 1<br>Participants will receive PF-07799544 | Drug: PF-07799544<br>* Tablet<br>* Other names: ARRY-134;|
| Experimental: Phase 1b Substudy A Dose Expansion Cohort 2<br>Participants will receive PF-07799544 and PF-07284890 | Drug: PF-07799544<br>* Tablet<br>* Other names: ARRY-134;Drug: PF-07284890<br>* Tablet<br>* Other names: ARRY-461;|
| Experimental: Phase 1b Substudy B Combination Dose Escalation<br>Participants will receive PF-07799544 and PF-07799933 | Drug: PF-07799544<br>* Tablet<br>* Other names: ARRY-134;Drug: PF-07799933<br>* Tablet<br>* Other names: ARRY-440;|
| Experimental: Phase 1b Substudy B Combination Dose Expansion<br>Participants will receive PF-07799544 and PF-07799933 | Drug: PF-07799544<br>* Tablet<br>* Other names: ARRY-134;Drug: PF-07799933<br>* Tablet<br>* Other names: ARRY-440;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with dose limiting toxicities (DLTs) Phase 1a monotherapy and Phase 1b combination therapy dose escalation | 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) | Cycle 1 (21 days) | 
| Overall response rate (ORR) (phase 1b expansion) | Response will be evaluated via radiographical tumor assessments by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) | Baseline to 2 years | 
| Number of participants with treatment-emergent adverse events (AEs) (phase 1a and 1b dose escalation phases) | AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy | Baseline to 28 days after last dose of study medication | 
| Number of participants with clinically significant change from baseline in laboratory abnormalities (phase 1a and phase 1b dose escalation phase) | Laboratory abnormalities as characterized by type, frequency, severity, and timing. | Baseline to 28 days after last dose of study treatment | 
| Number of participants with clinically significant change from baseline in vital sign abnormalities (phase 1a and phase 1b dose escalation phase) | Vital sign abnormalities as characterized by type, frequency, severity, and timing. | Baseline to 28 days after last dose of study treatment | 
| Number of participants with clinically significant change from baseline in physical exam abnormalities (phase 1a and phase 1b dose escalation phase) | Physical exam abnormalities as as graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. | Baseline to 28 days after last dose of study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR (phase 1a and phase 1b dose escalation) | ORR as assessed using the RECIST version 1.1. | Baseline to 2 years | 
| Intracranial response (all phases) | Intracranial response by RECIST version 1.1 (for brain metastases) | Baseline to 2 years | 
| Duration of response |  | Baseline to 2 years | 
| Number of participants with treatment-emergent adverse events (AEs) | AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy | Baseline to 2 years | 
| Number of participants with clinically significant change from baseline in laboratory abnormalities | Laboratory abnormalities as characterized by type, frequency, severity, and timing. | Baseline to 2 years | 
| PK parameters of PF-07799544, Single dose, maximum observed concentration (Cmax) | PK parameters of PF-07799544, Single dose, Cmax | Baseline to 2 years | 
| PK parameters of PF-07799544, Single dose, time to maximum plasma concentration (Tmax) | PK parameters of PF-07799544, Single dose, Tmax | Baseline to 2 years | 
| 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) | PK parameters of PF-07799544, Single dose, AUClast | Baseline to 2 years | 
| PK parameters of PF-07799544, Single dose, area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUCinf) | PK parameters of PF-07799544, Single dose, AUCinf | Baseline to 2 years | 
| PK parameters of PF-07799544, Single dose, terminal elimination half life (t½) | PK parameters of PF-07799544, Single dose, t½ | Baseline to 2 years | 
| PK parameters of PF-07799544, Single dose, apparent oral clearance (CL/F) | PK parameters of PF-07799544, Single dose, CL/F | Baseline to 2 years | 
| PK parameters of PF-07799544, Single dose, apparent volume of distribution (Vz/F) | PK parameters of PF-07799544, Single dose, Vz/F | Baseline to 2 years | 
| PK parameters of PF-07799544, Multiple dose, maximum observed concentration (Cmax) | PK parameters of PF-07799544, Multiple dose, Cmax | Baseline to 2 years | 
| PK parameters of PF-07799544, Multiple dose, time to maximum plasma concentration (Tmax) | PK parameters of PF-07799544, Multiple dose, Tmax | Baseline to 2 years | 
| PK parameters of PF-07799544, Multiple dose, area under the plasma concentration-time curve over the dosing interval (AUCτ) | PK parameters of PF-07799544, Multiple dose, AUCτ | Baseline to 2 years | 
| PK parameters of PF-07799544, Multiple dose, terminal elimination half life (t½) | PK parameters of PF-07799544, Multiple dose, t½ | Baseline to 2 years | 
| PK parameters of PF-07799544, Multiple dose, apparent oral clearance (CL/F) | PK parameters of PF-07799544, Multiple dose, CL/F | Baseline to 2 years | 
| PK parameters of PF-07799544, Multiple dose, apparent volume of distribution (Vz/F) | PK parameters of PF-07799544, Multiple dose, Vz/F | Baseline to 2 years | 
| PK parameters of PF-07284890, Single dose, maximum observed concentration (Cmax) | PK parameters of PF-07284890, Single dose, Cmax | Baseline to 2 years | 
| PK parameters of PF-07284890, Single dose, time to maximum plasma concentration (Tmax) | PK parameters of PF-07284890, Single dose, Tmax | Baseline to 2 years | 
| PK parameters of PF-07284890, Single dose, area under the plasma concentration-time curve from time 0 to the last time point of quantifiable concentration (AUClast) | PK parameters of PF-07284890, Single dose, AUClast | Baseline to 2 years | 
| PK parameters of PF-07284890, Single dose, area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUCinf) | PK parameters of PF-07284890, Single dose, AUCinf | Baseline to 2 years | 
| PK parameters of PF-07284890, Single dose, terminal elimination half life (t½) | PK parameters of PF-07284890, Single dose, t½ | Baseline to 2 years | 
| PK parameters of PF-07284890, Single dose, apparent oral clearance (CL/F) | PK parameters of PF-07284890, Single dose, CL/F | Baseline to 2 years | 
| PK parameters of PF-07284890, Single dose, apparent volume of distribution (Vz/F) | PK parameters of PF-07284890, Single dose, Vz/F | Baseline to 2 years | 
| PK parameters of PF-07284890, Multiple dose, maximum observed concentration (Cmax) | PK parameters of PF-07284890, Multiple dose, Cmax | Baseline to 2 years | 
| PK parameters of PF-07284890, Multiple dose, time to maximum plasma concentration (Tmax) | PK parameters of PF-07284890, Multiple dose, Tmax | Baseline to 2 years | 
| PK parameters of PF-07284890, Multiple dose, area under the plasma concentration-time curve over the dosing interval (AUCτ) | PK parameters of PF-07284890, Multiple dose, AUCτ | Baseline to 2 years | 
| PK parameters of PF-07284890, Multiple dose, terminal elimination half life (t½) | PK parameters of PF-07284890, Multiple dose, t½ | Baseline to 2 years | 
| PK parameters of PF-07284890, Multiple dose, apparent oral clearance (CL/F) | PK parameters of PF-07284890, Multiple dose, CL/F | Baseline to 2 years | 
| PK parameters of PF-07284890, Multiple dose, apparent volume of distribution (Vz/F) | PK parameters of PF-07284890, Multiple dose, Vz/F | Baseline to 2 years | 
| PK parameters of PF-07799933, Single dose, maximum observed concentration (Cmax) | PK parameters of PF-07799933, Single dose, Cmax | Baseline to 2 years | 
| PK parameters of PF-07799933, Single dose, time to maximum plasma concentration (Tmax) | PK parameters of PF-07799933, Single dose, Tmax | Baseline to 2 years | 
| 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) | PK parameters of PF-07799933, Single dose, AUClast | Baseline to 2 years | 
| PK parameters of PF-07799933, Single dose, area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUCinf) | PK parameters of PF-07799933, Single dose, AUCinf | Baseline to 2 years | 
| PK parameters of PF-07799933, Single dose, terminal elimination half life (t½) | PK parameters of PF-07799933, Single dose, t½ | Baseline to 2 years | 
| PK parameters of PF-07799933, Single dose, apparent oral clearance (CL/F) | PK parameters of PF-07799933, Single dose, CL/F | Baseline to 2 years | 
| PK parameters of PF-07799933, Single dose, apparent volume of distribution (Vz/F) | PK parameters of PF-07799933, Single dose, Vz/F | Baseline to 2 years | 
| PK parameters of PF-07799933, Multiple dose, maximum observed concentration (Cmax) | PK parameters of PF-07799933, Multiple dose, Cmax | Baseline to 2 years | 
| PK parameters of PF-07799933, Multiple dose, time to maximum plasma concentration (Tmax) | PK parameters of PF-07799933, Multiple dose, Tmax | Baseline to 2 years | 
| PK parameters of PF-07799933, Multiple dose, area under the plasma concentration-time curve over the dosing interval (AUCτ) | PK parameters of PF-07799933, Multiple dose, AUCτ | Baseline to 2 years | 
| PK parameters of PF-07799933, Multiple dose, terminal elimination half life (t½) | PK parameters of PF-07799933, Multiple dose, t½ | Baseline to 2 years | 
| PK parameters of PF-07799933, Multiple dose, apparent oral clearance (CL/F) | PK parameters of PF-07799933, Multiple dose, CL/F | Baseline to 2 years | 
| PK parameters of PF-07799933, Multiple dose, apparent volume of distribution (Vz/F) | PK parameters of PF-07799933, Multiple dose, Vz/F | Baseline to 2 years | 
| Number of participants with clinically significant change from baseline in vital sign abnormalities | Vital sign abnormalities as characterized by type, frequency, severity, and timing. | Baseline to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Proto-Oncogene Proteins B-raf, Brain neoplasms, Melanoma, Carcinoma, Non-Small-Cell Lung, Neoplasm by Histologic Type, CRC, MAPK