A Study to Learn About the Study Medicine Called PF-07799933 in People With Advanced Solid Tumors With BRAF Alterations.

Официальное название

A PHASE 1, OPEN-LABEL, DOSE ESCALATION AND DOSE EXPANSION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND ANTI TUMOR ACTIVITY OF PF-07799933 (ARRY-440) AS A SINGLE AGENT AND IN COMBINATION THERAPY IN PARTICIPANTS 16 YEARS AND OLDER WITH ADVANCED SOLID TUMORS WITH BRAF ALTERATIONS

Обзор

The purpose of this clinical trial is to learn about the safety and effects of the study medicine (called PF-07799933) administered as a single agent and in combination with other study medicines in people with solid tumors. This study is seeking participants who have an advanced solid tumor with a certain type of abnormal gene called "BRAF" and available treatments are no longer effective in controlling their cancer. All participants in this study will receive PF-07799933. PF-07799933 comes as a tablet to take by mouth, 2 times a day. Depending on the part of the study, participants may also receive another study medicine: * People with melanoma or other solid tumors may also receive binimetinib. Binimetinib comes as a tablet to take by mouth, 2 times a day. * People with colorectal cancer may also receive cetuximab or cetuximab and mFOLFOX6 (Chemotherapy regimen). Cetuximab will be given weekly (or every two weeks) in the clinic as a shot given in the vein or port (intravenous, IV). 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.

Вмешательства

• Препарат PF-07799933
  Tablet
• Препарат binimetinib
  Tablet
• Биопрепарат cetuximab
  Injection for intravenous use
• Препарат midazolam
  syrup
• Препарат fluorouracil
  Injection for intravenous use
• Препарат leucovorin
  Injection for intravenous use
• Препарат oxaliplatin
  Injection for intravenous use

Первичные конечные точки

• Number of participants with dose limiting toxicities (DLTs) (Part 1 and Part 2) [Срок оценки: Cycle 1 (21 days)]
• Number of participants with treatment-emergent adverse events (AEs) (Part 1 and Part 2) [Срок оценки: Baseline to 28 days after last dose of study medication]
• Number of participants with clinically significant change from baseline in laboratory abnormalities (Part 1 and Part 2) [Срок оценки: Baseline to 28 days after last dose of study treatment]
• Number of participants with clinically significant change from baseline in vital sign abnormalities (Part 1 and Part 2) [Срок оценки: Baseline to 28 days after last dose of study treatment]
• Dose interruptions due to AEs (Part 1 and Part 2) [Срок оценки: Baseline to 2 years]
• Dose dose modifications due to AEs (Part 1 and Part 2) [Срок оценки: Baseline to 2 years]
• Discontinuations due to AEs (Part 1 and Part 2) [Срок оценки: Baseline to 2 years]
• Overall response rate (ORR) (Part 3) [Срок оценки: Baseline to 2 years]
• Number of participants with clinically significant physical exam abnormalities (Part 1 and Part 2) [Срок оценки: Baseline to 28 days after last dose of study treatment]

Вторичные конечные точки (12)

• Part 1 and Part 2: ORR [Срок оценки: Baseline to 2 years]
• Part 1/2/3: Intracranial response [Срок оценки: Baseline to 2 years]
• Part 1 and Part 2: Duration of response [Срок оценки: Baseline to 2 years]
• Part 3: Number of participants with treatment-emergent adverse events (AEs) [Срок оценки: Baseline to 2 years]
• Part 3: Number of participants with clinically significant change from baseline in laboratory abnormalities [Срок оценки: Baseline to 2 years]
• Part 3: Number of participants with clinically significant change from baseline in vital sign abnormalities [Срок оценки: Baseline to 2 years]
• Part 3: Dose interruptions due to AEs [Срок оценки: Baseline to 2 years]
• Part 3: Dose dose modifications due to AEs [Срок оценки: Baseline to 2 years]
• Part 3: Discontinuations due to AEs [Срок оценки: Baseline to 2 years]
• Part 3: Time to event endpoints in each combination [Срок оценки: Baseline to 2 years]
• Part 3: Disease Control Rate (DCR) [Срок оценки: Baseline to 2 years]
• Part 1/2/3: PK parameters of PF-07799933, Single dose, maximum observed concentration (Cmax) [Срок оценки: Baseline to 2 years]

Критерии участия

This study is seeking participants who meet the following key eligibility criteria:

Критерии включения

• Diagnosis of advanced/metastatic solid tumor including primary brain tumor.
• Qualifying BRAF alteration (V600 or non-V600 Class II/Class III BRAF alteration), in tumor tissue and/or blood (ie circulating tumor deoxyribonucleic acid \[DNA\], or ctDNA).
• Disease progressed during/following last prior treatment and no satisfactory alternative treatment options (Part 1, Part 2 (doublet), and Part 3 (cohorts 2, 3, 6, 7)).
• Tumor specific cohorts (melanoma, colorectal cancer) must have received specific prior approved therapies
• Part 3 (Cohort 1) (BRAF V600 mutant melanoma): Prior BRAF V600 inhibitor therapy required, prior MEK inhibitor therapy required, and immune checkpoint inhibitor therapy required.
• Part 3 (Cohort 4) (BRAF V600E CRC): Minimum of 2 cycles of prior 5-FU based chemotherapy required. No prior BRAF inhibitor/EGFR inhibitor allowed. Participants with MSI-H/dMMR mCRC should receive prior immune checkpoint inhibitor therapy.
• Part 3 (Cohort 5) (BRAF V600E CRC): No more than 2 cycles of prior 5-FU based chemotherapy allowed. No prior BRAF inhibitor/EGFR inhibitors allowed. Participants with MSI-H/dMMR mCRC should receive prior immune checkpoint inhibitor therapy.

Критерии исключения

• Brain metastasis larger than 4 cm
• Systemic anti-cancer therapy or small molecule therapeutics ongoing at the start of study treatment.
• History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO; history of retinal degenerative disease.
• Concurrent neuromuscular disorder associated with elevated creatine kinase (CK).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 31 центр

• Highlands Oncology Group, PA — Fayetteville
• Highlands Oncology Group, PA — Rogers
• Highlands Oncology Group, PA — Springdale
• Clinical and Translational Research Center (CTRC) — Aurora
• UCHealth Sue Anschutz-Rodgers Eye Center — Aurora
• University of Colorado Hospital - Anschutz Cancer Pavilion (ACP) — Aurora
• University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP) — Aurora
• University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP) — Aurora
• … и ещё 23 центра

Канада · 5 центров

• The Ottawa Hospital - General Campus — Ottawa
• Princess Margaret Cancer Centre — Toronto
• University Health Network — Toronto
• Jewish General Hospital — Montreal
• McGill University Health Centre — Montreal

Израиль · 4 центра

• Sourasky Medical Center — Tel Aviv
• Hadassah Medical Center — Jerusalem
• Sheba Medical Center — Ramat Gan
• Rambam Health Care Campus — Haifa

Идентификаторы

NCT: NCT05355701 · C4761001 · BRAF Class 2

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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