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

NCT ID: NCT05668585

Last Updated: 2025-11-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

89 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-12-08

Study Completion Date

2025-11-05

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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).

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Solid Tumors Melanoma NSCLC CRC ATC

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Phase 1: Arm A: CFT1946

Approximately 40 subjects with V600 Solid Tumors (non-CNS) (post BRAF inhibitor for NSCLC, CRC, melanoma, ATC)

Group Type EXPERIMENTAL

CFT1946

Intervention Type DRUG

Specified oral dose on specified day

Phase 1: Arm B: CFT1946 + trametinib

Approximately 28 subjects with V600 Solid Tumors (non-CNS) (post BRAF inhibitor for NSCLC, CRC, melanoma)

Group Type EXPERIMENTAL

CFT1946

Intervention Type DRUG

Specified oral dose on specified day

Trametinib

Intervention Type DRUG

Specified oral dose on specified day

Phase 2: Arm A1: CFT1946

Approximately 30 subjects with V600 melanoma or NSCLC (post BRAF inhibitor)

Group Type EXPERIMENTAL

CFT1946

Intervention Type DRUG

Specified oral dose on specified day

Phase 2: Arm B1: CFT1946 + trametinib

Approximately 20 subjects with V600 melanoma or NSCLC (post BRAF Inhibitor)

Group Type EXPERIMENTAL

CFT1946

Intervention Type DRUG

Specified oral dose on specified day

Trametinib

Intervention Type DRUG

Specified oral dose on specified day

Phase 1: Arm C: CFT1946 + cetuximab

Approximately 30 subjects with CRC (post BRAF inhibitor)

Group Type EXPERIMENTAL

CFT1946

Intervention Type DRUG

Specified oral dose on specified day

Cetuximab

Intervention Type DRUG

Specified intravenous dose on specified day

Phase 2: Arm C1: CFT1946 + cetuximab

Approximately 40 subjects with CRC (post BRAF inhibitor)

Group Type EXPERIMENTAL

CFT1946

Intervention Type DRUG

Specified oral dose on specified day

Cetuximab

Intervention Type DRUG

Specified intravenous dose on specified day

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

CFT1946

Specified oral dose on specified day

Intervention Type DRUG

Trametinib

Specified oral dose on specified day

Intervention Type DRUG

Cetuximab

Specified intravenous dose on specified day

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Subject (or legally authorized representative, where applicable) is willing and able to provide signed informed consent and can follow protocol requirements
2. Subject is ≥18 years of age at time of informed consent
3. Eastern Cooperative Oncology Group performance status of 0 or 1
4. Subject has documented evidence of a BRAF V600 mutation obtained from tumor tissue or liquid biopsy: (other protocol conditions may apply)
5. 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:

1. 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.
2. 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.
3. ATC: Subjects must have received SoC therapy options including BRAF inhibitor if available and of benefit to the subject
4. 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
6. Subject has measurable disease per RECIST v1.1
7. Adequate bone marrow, liver, renal, and cardiac function
8. 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
9. A male subject must agree to comply with protocol conditions relating to the use of contraception, sperm and blood donation
10. Subject can safely swallow a tablet or pill

Exclusion Criteria

1. Subject has had major surgery within 21 days prior to the planned first dose. Minor surgery is permitted within 21 days prior to enrollment
2. 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.
3. 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
4. Subject with history of thromboembolic or cerebrovascular events ≤6 months as defined in the protocol
5. Subject with impaired cardiac function or clinically significant cardiac disease, as defined in the protocol
6. Subject with history of uncontrolled diabetes mellitus (only for subjects who will receive CFT1946 + trametinib)
7. 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)
8. Subject has received live, attenuated vaccine within 28 days prior to first dose administration
9. Subject has history of pneumonitis or interstitial lung disease
10. Subject has history of uveitis
11. Subject has clinically significant gastrointestinal abnormalities.
12. Subject has known human immunodeficiency virus (HIV) infection (with exceptions)
13. Subject has history of or known HBV or active HCV infection
14. Subject has concurrent administration of strong CYP3A4/5 inhibitors and inducers, including any herbal medications/supplements
15. Subject has presence of Grade ≥2 toxicity due to prior cancer therapy, excepting alopecia and hypothyroidism requiring thyroid replacement therapy
16. 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
17. Subject is pregnant, breastfeeding, or expecting to conceive or father children any time during the study
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

C4 Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

University of Arizona - Cancer Center

Tucson, Arizona, United States

Site Status

Florida Cancer Specialists

Sarasota, Florida, United States

Site Status

Community Health Network

Indianapolis, Indiana, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Allina Health System DBA Virginia Piper Cancer Institute

Minneapolis, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Sarah Cannon and HCA Research Institute

Nashville, Tennessee, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Virginia Cancer Specialists (NEXT Oncology Virginia)

Fairfax, Virginia, United States

Site Status

University of Wisconsin

Madison, Wisconsin, United States

Site Status

Institut Bergonie

Bordeaux, , France

Site Status

Chu de Lille

Lille, , France

Site Status

Centre Leon Berard

Lyon, , France

Site Status

IUCT Oncopole

Toulouse, , France

Site Status

KEM | Evang. Kliniken Essen-Mitte gGmbH

Essen, , Germany

Site Status

Universitaetsklinikum Essen

Essen, , Germany

Site Status

NEXT Oncology Barcelona

Barcelona, , Spain

Site Status

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Site Status

Complejo Hospitalario de Jaen

Jaén, , Spain

Site Status

Hospital General Universitario Gregorio Maranon

Madrid, , Spain

Site Status

South Texas Accelerated Research Therapeutics (START) Madrid - Hospital Fundacion Jiminez Diaz

Madrid, , Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Site Status

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Site Status

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States France Germany Spain United Kingdom

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

CFT1946-1101

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

QTX3046 in Patients With KRAS G12D Mutations
NCT06428500 ACTIVE_NOT_RECRUITING PHASE1
A Phase 1-2 Study of ST101 in Patients With Advanced Solid Tumors
NCT04478279 ACTIVE_NOT_RECRUITING PHASE1/PHASE2
Safety Study of FP-1039 To Treat Cancer
NCT00687505 COMPLETED PHASE1
Study of ART6043 in Advanced/Metastatic Solid Tumors Patients
NCT05898399 ACTIVE_NOT_RECRUITING PHASE1/PHASE2