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

NCT05668585 | Completed Phase 1 FDA Drug

• 1 other identifier: CFT1946-1101
• Study Type: interventional
• Target: 89
• Locations: 5 countries
• Sites: 26

Brief Summary

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).

Conditions

Solid Tumors; Melanoma; NSCLC; CRC; ATC

Keywords

Solid Tumors; Melanoma; NSCLC; ATC; BRAF mutant; CRC

Outcome Measures

Primary Outcomes (8)

• Frequency and severity of AEs and SAEs

  Phase 1

  From enrollment until 30 days after completion of study treatment

• Incidence of dose limiting toxicities (DLTs)

  Phase 1

  From enrollment until 28 days after first dose

• Number of subjects with changes between baseline and post-baseline safety assessments based on safety laboratory results graded by CTCAE v5.0

  Phase 1

  From enrollment until 30 days after completion of study treatment

• Frequency of dose interruptions and dose reductions

  Phase 1

  From enrollment until 30 days after completion of study treatment

• Frequency of AEs leading to discontinuation of study treatment(s)

  Phase 1

  From enrollment until 30 days after completion of study treatment

• Overall response rate (ORR)

  Phase 2 only according to RECIST v1.1 criteria

  Up to approximately 43 months

• Disease control rate (DCR) at 3, 6, and 12 months

  Phase 2

  Up to 12 months

• Duration of Response (DOR)

  Phase 2

  Up to approximately 43 months

Secondary Outcomes (11)

• Frequency and severity of AEs and SAEs

  From enrollment until 30 days after completion of study treatment

• Number of subjects with changes between baseline and post-baseline safety assessments based on safety laboratory results graded by CTCAE v5.0

  From enrollment until 30 days after completion of study treatment

• Frequency of dose interruptions and dose reductions

  From enrollment until 30 days after completion of study treatment

• Frequency of AEs leading to discontinuation of study treatment(s)

  From enrollment until 30 days after completion of study treatment

• Plasma concentration of CFT1946 to characterize the pharmacokinetics (PK) parameters of CFT1946 monotherapy and in combination with trametinib

  Up to approximately 20 weeks

Study Arms (6)

Phase 1: Arm A: CFT1946

EXPERIMENTAL

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

Drug: CFT1946

Phase 1: Arm B: CFT1946 + trametinib

EXPERIMENTAL

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

Drug: CFT1946; Drug: Trametinib

Phase 2: Arm A1: CFT1946

EXPERIMENTAL

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

Drug: CFT1946

Phase 2: Arm B1: CFT1946 + trametinib

EXPERIMENTAL

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

Drug: CFT1946; Drug: Trametinib

Phase 1: Arm C: CFT1946 + cetuximab

EXPERIMENTAL

Approximately 30 subjects with CRC (post BRAF inhibitor)

Drug: CFT1946; Drug: Cetuximab

Phase 2: Arm C1: CFT1946 + cetuximab

EXPERIMENTAL

Approximately 40 subjects with CRC (post BRAF inhibitor)

Drug: CFT1946; Drug: Cetuximab

Interventions

CFT1946 DRUG

Specified oral dose on specified day

Phase 1: Arm A: CFT1946; Phase 1: Arm B: CFT1946 + trametinib; Phase 1: Arm C: CFT1946 + cetuximab; Phase 2: Arm A1: CFT1946; Phase 2: Arm B1: CFT1946 + trametinib; Phase 2: Arm C1: CFT1946 + cetuximab

Trametinib DRUG

Specified oral dose on specified day

Phase 1: Arm B: CFT1946 + trametinib; Phase 2: Arm B1: CFT1946 + trametinib

Cetuximab DRUG

Specified intravenous dose on specified day

Phase 1: Arm C: CFT1946 + cetuximab; Phase 2: Arm C1: CFT1946 + cetuximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

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

Sponsors & Collaborators

• C4 Therapeutics, Inc.: lead

Study Sites (26)

University of Arizona - Cancer Center

Tucson, Arizona, 85719, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Community Health Network

Indianapolis, Indiana, 46250, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Allina Health System DBA Virginia Piper Cancer Institute

Minneapolis, Minnesota, 55407, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

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

New York, New York, 10021, United States

Location

Sarah Cannon and HCA Research Institute

Nashville, Tennessee, 37203, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Virginia Cancer Specialists (NEXT Oncology Virginia)

Fairfax, Virginia, 22031, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Chu de Lille

Lille, 59037, France

Location

Centre Leon Berard

Lyon, 69008, France

Location

IUCT Oncopole

Toulouse, 31059, France

Location

KEM | Evang. Kliniken Essen-Mitte gGmbH

Essen, 45136, Germany

Location

Universitaetsklinikum Essen

Essen, 45147, Germany

Location

NEXT Oncology Barcelona

Barcelona, 08023, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Complejo Hospitalario de Jaen

Jaén, 23007, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

Location

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

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Melanoma

Interventions

trametinib; Cetuximab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2022
• First Posted: December 30, 2022
• Study Start: December 8, 2022
• Primary Completion: November 5, 2025
• Study Completion: November 5, 2025
• Last Updated: November 21, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

ES (7); GB (2); DE (2); US (11); FR (4)