A Study to Characterize the Safety, Tolerability, and Preliminary Efficacy of CFT1946 as Monotherapy and Combination Therapy in Subjects With BRAF V600 Mutant Solid Tumors

Completed · Phase 1

Conditions studied: Solid Tumors, Melanoma, NSCLC, CRC, ATC

In brief

The purpose of this study is to evaluate the safety and tolerability of CFT1946 as well as to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of CFT1946 as monotherapy (Arm A) and in combination with trametinib (CFT1946 + trametinib; Arm B) or Cetuximab (CFT1946 + cetuximab; Arm C).

Key facts

Study ID: NCT05668585
Run by: C4 Therapeutics, Inc.
People needed: 89
Starts: 2022-12-08
Expected to finish: 2025-11-05
Last updated by the study team: 2025-11-21

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Subject (or legally authorized representative, where applicable) is willing and able to provide signed informed consent and can follow protocol requirements
Subject is ≥18 years of age at time of informed consent
Eastern Cooperative Oncology Group performance status of 0 or 1
Subject has documented evidence of a BRAF V600 mutation obtained from tumor tissue or liquid biopsy: (other protocol conditions may apply)
Subject must have received ≥1 prior line of SoC therapy for their unresectable locally advanced or metastatic disease with disease progression on or after last prior treatment. Prior regimens for these subjects vary by indication and investigational arm, but must have included the following:
Melanoma or NSCLC (Phase 1 and Phase 2 Arms A1 and B1): Prior receipt of a BRAF inhibitor and an immune checkpoint inhibitor (any sequence or combination). Prior (neo)adjuvant immunotherapy may be acceptable.
CRC: Subjects must have received no more than 4 lines of prior therapy which includes systemic chemotherapy-based regimen per SoC for unresectable locally advanced or metastatic disease, and previous treatment with BRAF inhibitor in combination with an EGFR monoclonal antibody. Subjects with documented MSI-H or dMMR CRC must have received prior immunotherapy. Subjects with MSS disease must have received at least 2 prior treatments. Subjects who received neo(adjuvant) chemotherapy regimens may be eligible.
ATC: Subjects must have received SoC therapy options including BRAF inhibitor if available and of benefit to the subject
Other BRAF V600 mutant solid tumors (non-CNS): Subjects must have received SoC therapy options per their Investigator's best judgment, including BRAF inhibitor if available and of benefit to the subject
Subject has measurable disease per RECIST v1.1
Adequate bone marrow, liver, renal, and cardiac function
A female subject may be eligible if not pregnant, planning a pregnancy, not breast feeding, a women of non-child bearing potential or a WOCBP willing to comply with protocol conditions relating to the use contraception, ova or blood donation and pregnancy testing prior to the first dose
A male subject must agree to comply with protocol conditions relating to the use of contraception, sperm and blood donation
Subject can safely swallow a tablet or pill
Other protocol defined exclusion criteria may apply

You may not qualify if…

Subject has had major surgery within 21 days prior to the planned first dose. Minor surgery is permitted within 21 days prior to enrollment
Subject with CNS involvement (primary tumor or metastatic disease), except if clinically stable, have no evidence of new or enlarging brain metastases and are on stable or tapering doses of steroids for at least 7 days prior to first dose. Subjects with untreated brain metastases may be eligible to enter without prior radiation therapy.
Subject with known malignancy other than trial indication that is progressing or has required treatment within the past 3 years, except for conditions that have undergone potentially curative therapy
Subject with history of thromboembolic or cerebrovascular events ≤6 months as defined in the protocol
Subject with impaired cardiac function or clinically significant cardiac disease, as defined in the protocol
Subject with history of uncontrolled diabetes mellitus (only for subjects who will receive CFT1946 + trametinib)
Subject with history or current evidence of retinal vein occlusion (RVO), chorioretinopathy, or current risk factors for RVO (only for subjects who will receive CFT1946 + trametinib)
Subject has received live, attenuated vaccine within 28 days prior to first dose administration
Subject has history of pneumonitis or interstitial lung disease
Subject has history of uveitis
Subject has clinically significant gastrointestinal abnormalities.
Subject has known human immunodeficiency virus (HIV) infection (with exceptions)
Subject has history of or known HBV or active HCV infection
Subject has concurrent administration of strong CYP3A4/5 inhibitors and inducers, including any herbal medications/supplements
Subject has presence of Grade ≥2 toxicity due to prior cancer therapy, excepting alopecia and hypothyroidism requiring thyroid replacement therapy
Subject has initiation or receipt of the following ≤7 days prior to first dose administration: Hematopoietic colony-stimulating growth factors, transfusion of packed red blood cells (pRBC), and transfusion of platelets
Subject is pregnant, breastfeeding, or expecting to conceive or father children any time during the study
Other protocol defined exclusion criteria may apply

Where it is running

University of Arizona - Cancer Center — Tucson, Arizona, United States
Florida Cancer Specialists — Sarasota, Florida, United States
Community Health Network — Indianapolis, Indiana, United States
Dana-Farber Cancer Institute — Boston, Massachusetts, United States
Allina Health System DBA Virginia Piper Cancer Institute — Minneapolis, Minnesota, United States
Washington University School of Medicine — St Louis, Missouri, United States
David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center — New York, New York, United States
Sarah Cannon and HCA Research Institute — Nashville, Tennessee, United States
MD Anderson Cancer Center — Houston, Texas, United States
Virginia Cancer Specialists (NEXT Oncology Virginia) — Fairfax, Virginia, United States
University of Wisconsin — Madison, Wisconsin, United States
Institut Bergonie — Bordeaux, France
Chu de Lille — Lille, France
Centre Leon Berard — Lyon, France
IUCT Oncopole — Toulouse, France
KEM | Evang. Kliniken Essen-Mitte gGmbH — Essen, Germany
Universitaetsklinikum Essen — Essen, Germany
NEXT Oncology Barcelona — Barcelona, Spain
Hospital Universitario Vall d'Hebron — Barcelona, Spain
Complejo Hospitalario de Jaen — Jaén, Spain
Hospital General Universitario Gregorio Maranon — Madrid, Spain
South Texas Accelerated Research Therapeutics (START) Madrid - Hospital Fundacion Jiminez Diaz — Madrid, Spain
Hospital Universitario 12 de Octubre — Madrid, Spain
Hospital Clinico Universitario de Valencia — Valencia, Spain
Beatson West of Scotland Cancer Centre — Glasgow, United Kingdom

Full record on ClinicalTrials.gov

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