Solid TumorsPhase 1NCT05668585
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
A Phase 1 study testing CFT1946, Trametinib and Cetuximab in people with Solid Tumors and Melanoma, run by C4 Therapeutics, Inc. at 26 sites in 5 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors, Melanoma, NSCLC
- What is being tested?
- CFT1946, Trametinib and Cetuximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 89 participants
- Where
- 26 sitesin 5 countries
- Study dates
- 8 Dec 2022to 5 Nov 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
26 sites in 5 countries.
26 sites in 5 countries
United States11 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Virginia Cancer Specialists (NEXT Oncology Virginia)
Fairfax, Virginia, 22031
MD Anderson Cancer Center
Houston, Texas, 77030
Community Health Network
Indianapolis, Indiana, 46250
University of Wisconsin
Madison, Wisconsin, 53792
Allina Health System DBA Virginia Piper Cancer Institute
Minneapolis, Minnesota, 55407
Sarah Cannon and HCA Research Institute
Nashville, Tennessee, 37203
David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
New York, New York, 10021
Florida Cancer Specialists
Sarasota, Florida, 34232
Washington University School of Medicine
St Louis, Missouri, 63110
University of Arizona - Cancer Center
Tucson, Arizona, 85719
Spain7 sites
NEXT Oncology Barcelona
Barcelona, 08023
Hospital Universitario Vall d'Hebron
Barcelona, 08035
Complejo Hospitalario de Jaen
Jaén, 23007
Hospital General Universitario Gregorio Maranon
Madrid, 28007
South Texas Accelerated Research Therapeutics (START) Madrid - Hospital Fundacion Jiminez Diaz
Madrid, 28040
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Clinico Universitario de Valencia
Valencia, 46010
France4 sites
Institut Bergonie
Bordeaux, 33076
Chu de Lille
Lille, 59037
Centre Leon Berard
Lyon, 69008
IUCT Oncopole
Toulouse, 31059
Germany2 sites
KEM | Evang. Kliniken Essen-Mitte gGmbH
Essen, 45136
Universitaetsklinikum Essen
Essen, 45147
United Kingdom2 sites
Beatson West of Scotland Cancer Centre
Glasgow, G12 0YN
The Christie NHS Foundation Trust
Manchester, M20 4BX
About this study
Official title: A Phase 1/2 Open-Label Multicenter Trial to Characterize the Safety, Tolerability, and Preliminary Efficacy of CFT1946 as Monotherapy and Combination Therapy in Subjects With BRAF V600 Mutant Solid Tumors
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).
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CFT1946Drug
Specified oral dose on specified day
TrametinibDrug
Specified oral dose on specified day
CetuximabDrug
Specified intravenous dose on specified day
| Study group | Role | What they receive |
|---|---|---|
| Phase 1: Arm A: CFT1946 | Experimental | Approximately 40 subjects with V600 Solid Tumors (non-CNS) (post BRAF inhibitor for NSCLC, CRC, melanoma, ATC) Receives: 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) Receives: Drug: CFT1946; Drug: Trametinib |
| Phase 2: Arm A1: CFT1946 | Experimental | Approximately 30 subjects with V600 melanoma or NSCLC (post BRAF inhibitor) Receives: Drug: CFT1946 |
| Phase 2: Arm B1: CFT1946 + trametinib | Experimental | Approximately 20 subjects with V600 melanoma or NSCLC (post BRAF Inhibitor) Receives: Drug: CFT1946; Drug: Trametinib |
| Phase 1: Arm C: CFT1946 + cetuximab | Experimental | Approximately 30 subjects with CRC (post BRAF inhibitor) Receives: Drug: CFT1946; Drug: Cetuximab |
| Phase 2: Arm C1: CFT1946 + cetuximab | Experimental | Approximately 40 subjects with CRC (post BRAF inhibitor) Receives: Drug: CFT1946; Drug: Cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency and severity of AEs and SAEs
Phase 1
Measured: From enrollment until 30 days after completion of study treatment
Incidence of dose limiting toxicities (DLTs)
Phase 1
Measured: 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
Measured: From enrollment until 30 days after completion of study treatment
Frequency of dose interruptions and dose reductions
Phase 1
Measured: From enrollment until 30 days after completion of study treatment
Frequency of AEs leading to discontinuation of study treatment(s)
Phase 1
Measured: From enrollment until 30 days after completion of study treatment
Overall response rate (ORR)
Phase 2 only according to RECIST v1.1 criteria
Measured: Up to approximately 43 months
Disease control rate (DCR) at 3, 6, and 12 months
Phase 2
Measured: Up to 12 months
Duration of Response (DOR)
Phase 2
Measured: Up to approximately 43 months
Secondary outcomes (11)
Frequency and severity of AEs and SAEs
Phase 2
Measured: 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
Phase 2
Measured: From enrollment until 30 days after completion of study treatment
Frequency of dose interruptions and dose reductions
Phase 2
Measured: From enrollment until 30 days after completion of study treatment
Frequency of AEs leading to discontinuation of study treatment(s)
Phase 2
Measured: 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
Phase 1 and Phase 2
Measured: Up to approximately 20 weeks
PK-QTcF relationship
Phase 1 and Phase 2
Measured: Up to approximately 8 weeks
Overall response rate (ORR)
Phase 1
Measured: Up to approximately 43 months
Disease control rate (DCR) at 3, 6, and 12 months
Phase 1
Measured: Up to 12 months
Progression-free survival (PFS)
Phase 1 and Phase 2
Measured: Up to approximately 43 months
Duration of response (DOR)
Phase 1
Measured: Up to approximately 43 months
Assess the pharmacodynamics by percent reduction from baseline of target protein
Tumor BRAF-V600 degradation at scheduled timepoints
Measured: At multiple time points up to 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2022
- Study start8 Dec 2022
- Primary completion5 Nov 2025
- Study completion5 Nov 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 89 participants (actual)
Sponsor and investigators
- Lead sponsor
- C4 Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05668585
- Sponsor's protocol ID
- CFT1946-1101
- Status last verified
- Nov 2025
- First submitted
- 6 Dec 2022
- Last updated
- 21 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Open-Label Multicenter Trial to Characterize the Safety, Tolerability, and Preliminary Efficacy of CFT1946 as Monotherapy and Combination Therapy in Subjects With BRAF V600 Mutant Solid Tumors
- ClinicalTrials.gov ID
- NCT05668585
- Acronym / sponsor ID
- CFT1946-1101
- Conditions
- Solid Tumors, Melanoma, NSCLC, CRC, ATC
- Keywords
- Solid Tumors, Melanoma, NSCLC, ATC, BRAF mutant, CRC
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 89 participants (actual)
- Lead sponsor
- C4 Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 8 Dec 2022 (actual)
- Primary completion
- 5 Nov 2025 (actual)
- Study completion
- 5 Nov 2025 (actual)
- First posted
- 30 Dec 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Phase 1: Arm A: CFT1946 | Experimental | Drug: CFT1946Approximately 40 subjects with V600 Solid Tumors (non-CNS) (post BRAF inhibitor for NSCLC, CRC, melanoma, ATC) |
| Phase 1: Arm B: CFT1946 + trametinib | Experimental | Drug: CFT1946, Drug: TrametinibApproximately 28 subjects with V600 Solid Tumors (non-CNS) (post BRAF inhibitor for NSCLC, CRC, melanoma) |
| Phase 2: Arm A1: CFT1946 | Experimental | Drug: CFT1946Approximately 30 subjects with V600 melanoma or NSCLC (post BRAF inhibitor) |
| Phase 2: Arm B1: CFT1946 + trametinib | Experimental | Drug: CFT1946, Drug: TrametinibApproximately 20 subjects with V600 melanoma or NSCLC (post BRAF Inhibitor) |
| Phase 1: Arm C: CFT1946 + cetuximab | Experimental | Drug: CFT1946, Drug: CetuximabApproximately 30 subjects with CRC (post BRAF inhibitor) |
| Phase 2: Arm C1: CFT1946 + cetuximab | Experimental | Drug: CFT1946, Drug: CetuximabApproximately 40 subjects with CRC (post BRAF inhibitor) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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:
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CFT1946Specified oral dose on specified day | Drug | 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 |
| TrametinibSpecified oral dose on specified day | Drug | Phase 1: Arm B: CFT1946 + trametinib, Phase 2: Arm B1: CFT1946 + trametinib |
| CetuximabSpecified intravenous dose on specified day | Drug | Phase 1: Arm C: CFT1946 + cetuximab, Phase 2: Arm C1: CFT1946 + cetuximab |
Primary outcome
Frequency and severity of AEs and SAEs
Time frame: From enrollment until 30 days after completion of study treatment
Phase 1
Incidence of dose limiting toxicities (DLTs)
Time frame: From enrollment until 28 days after first dose
Phase 1
Number of subjects with changes between baseline and post-baseline safety assessments based on safety laboratory results graded by CTCAE v5.0
Time frame: From enrollment until 30 days after completion of study treatment
Phase 1
Frequency of dose interruptions and dose reductions
Time frame: From enrollment until 30 days after completion of study treatment
Phase 1
Frequency of AEs leading to discontinuation of study treatment(s)
Time frame: From enrollment until 30 days after completion of study treatment
Phase 1
Overall response rate (ORR)
Time frame: Up to approximately 43 months
Phase 2 only according to RECIST v1.1 criteria
Disease control rate (DCR) at 3, 6, and 12 months
Time frame: Up to 12 months
Phase 2
Duration of Response (DOR)
Time frame: Up to approximately 43 months
Phase 2
11 secondary outcomes
Frequency and severity of AEs and SAEs
Time frame: 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
Time frame: From enrollment until 30 days after completion of study treatment
Frequency of dose interruptions and dose reductions
Time frame: From enrollment until 30 days after completion of study treatment
Frequency of AEs leading to discontinuation of study treatment(s)
Time frame: 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
Time frame: Up to approximately 20 weeks
PK-QTcF relationship
Time frame: Up to approximately 8 weeks
Overall response rate (ORR)
Time frame: Up to approximately 43 months
Disease control rate (DCR) at 3, 6, and 12 months
Time frame: Up to 12 months
Progression-free survival (PFS)
Time frame: Up to approximately 43 months
Duration of response (DOR)
Time frame: Up to approximately 43 months
Assess the pharmacodynamics by percent reduction from baseline of target protein
Time frame: At multiple time points up to 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
26 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CFT1946, Trametinib and Cetuximab in people with Solid Tumors and Melanoma, run by C4 Therapeutics, Inc. at 26 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in United States, Spain, France, Germany, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency and severity of AEs and SAEs (time frame: From enrollment until 30 days after completion of study treatment). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Nov 2025.