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

Official title

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

Overview

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.

Interventions

• Drug PF-07799544
  Tablet
• Drug PF-07799933
  Tablet

Primary outcome measures

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

Secondary outcome measures (12)

• 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]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 58 centers

• 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
• … and 50 more centers

Canada · 8 centers

• 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

Israel · 5 centers

• Rabin Medical Center — Petah Tikva
• Sheba Medical Center — Ramat Gan
• Hadassah Medical Center — Jerusalem
• Soroka Medical Center — Beersheba
• … and 1 more center

Brazil · 4 centers

• 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

Australia · 3 centers

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

China · 3 centers

• Fujian Cancer Hospital — Fuzhou
• Zhejiang Cancer Hospital — Hangzhou
• The First Affiliated Hospital of Wenzhou Medical University — Wenzhou

Japan · 2 centers

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT05538130 · C4901001 · NCT05538130

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗