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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат PF-07799544
  Tablet
• Препарат PF-07799933
  Tablet

Первичные конечные точки

• Phase 1a monotherapy and Phase 1b combination dose escalation: Number of participants with dose limiting toxicities (DLTs) [Срок оценки: Cycle 1 (21 days)]
• Phase 1a monotherapy and Phase 1b combination dose escalation: Number of participants with treatment-emergent adverse events (AEs) [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Baseline to 28 days after last dose of study treatment]
• Phase 1b Dose Expansion: Overall response rate (ORR) [Срок оценки: Baseline to 2 years]

Вторичные конечные точки (12)

• Phase 1a monotherapy and Phase 1b combination dose escalation: ORR [Срок оценки: Baseline to 2 years]
• Phase 1b Dose Expansion: Number of participants with treatment-emergent adverse events (AEs) [Срок оценки: Baseline to 2 years]
• Phase 1b Dose Expansion: Number of participants with clinically significant change from baseline in vital sign abnormalities [Срок оценки: Baseline to 2 years]
• Phase 1b Dose Expansion: Number of participants with clinically significant change from baseline in laboratory abnormalities [Срок оценки: Baseline to 2 years]
• Phase 1b Dose Expansion: Duration of Response (Overall and in CNS) [Срок оценки: Baseline to 2 years]
• Phase 1b Dose Expansion: Intracranial response [Срок оценки: Baseline to 2 years]
• Phase 1b Dose Expansion: Progression Free Survival (PFS) [Срок оценки: Baseline to 2 years]
• PK Parameters: Maximum Observed Concentration (Cmax) [Срок оценки: Baseline to 2 years]
• PK Parameters: Maximum Plasma Concentration (Tmax) [Срок оценки: Baseline to 2 years]
• PK Parameters: Area Under Curve (AUC) [Срок оценки: Baseline to 2 years]
• PK Parameters: terminal elimination half-life (t½) [Срок оценки: Baseline to 2 years]
• PK Parameters: Apparent Oral Clearance (CL/F) [Срок оценки: Baseline to 2 years]

Критерии участия

Phase 1b Inclusion Criteria:

• Diagnosis of advanced/metastatic solid tumor (excluding colorectal cancer)
• Measurable disease by RECIST version 1.1
• Evidence of a BRAF V600 mutation
• Prior therapy per tumor cohort
• Adequate organ function per protocol

Phase 1b Exclusion Criteria:

• Other active malignancy within 3 years
• Presence of leptomeningeal disease
• History or current evidence of retinal vein occlusion (RVO) or history of retinal degenerative disease
• Concurrent neuromuscular disorder associated with elevated creatine kinase (CK)
• Active gastrointestinal disease as defined per protocol
• History of interstitial lung disease as defined per protocol

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 · 58 центров

• The Kirklin Clinic of UAB Hospital — Birmingham
• The University of Alabama at Birmingham — Birmingham
• University of Alabama at Birmingham - Phase I Clinical Trials Unit — Birmingham
• Highlands Oncology Group, PA — Fayetteville
• Highlands Oncology Group, PA — Rogers
• Highlands Oncology Group, PA — Springdale
• The Angeles Clinic and Research Institute- A Cedars-Sinai Affiliate — Los Angeles
• Keck Hospital of USC — Los Angeles
• … и ещё 50 центров

Канада · 8 центров

• Cross Cancer Institute — Edmonton
• Alberta Health Services and The Governors of The University of Alberta — Edmonton
• The Ottawa Hospital - General Campus — Ottawa
• Sunnybrook Research Institute — Toronto
• Princess Margaret Cancer Centre — Toronto
• Jewish General Hospital — Montreal
• McGill University Health Centre — Montreal
• Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésu — Québec

Израиль · 5 центров

• Rabin Medical Center — Petah Tikva
• Sheba Medical Center — Ramat Gan
• Hadassah Medical Center — Jerusalem
• Soroka Medical Center — Beersheba
• … и ещё 1 центр

Бразилия · 4 центра

• Hospital Nossa Senhora da Conceição — Porto Alegre
• ANIMI - Unidade de Tratamento Oncologico — Lages
• Centro de Oncologia - CEON+ - Unidade São Caetano do Sul — São Caetano do Sul
• IBCC - Núcleo de Pesquisa e Ensino — São Paulo

Австралия · 3 центра

• Peter MacCallum Cancer Centre — Melbourne
• The Alfred Hospital — Melbourne
• Royal Melbourne Hospital — Parkville

Китай · 3 центра

• Fujian Cancer Hospital — Фучжоу
• Zhejiang Cancer Hospital — Ханчжоу
• The First Affiliated Hospital of Wenzhou Medical University — Wenzhou

Япония · 2 центра

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT05538130 · C4901001 · NCT05538130

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗