ATC, CRC, Melanoma, NSCLC, Solid Tumors
Conditions
Keywords
Solid Tumors, Melanoma, NSCLC, ATC, BRAF mutant, CRC
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).
Interventions
DRUGCFT1946
Specified oral dose on specified day
DRUGTrametinib
Specified oral dose on specified day
DRUGCetuximab
Specified intravenous dose on specified day
Sponsors
C4 Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 Other protocol defined
Exclusion criteria
may apply
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency and severity of AEs and SAEs | From enrollment until 30 days after completion of study treatment | Phase 1 |
| Incidence of dose limiting toxicities (DLTs) | 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 | From enrollment until 30 days after completion of study treatment | Phase 1 |
| Frequency of dose interruptions and dose reductions | From enrollment until 30 days after completion of study treatment | Phase 1 |
| Frequency of AEs leading to discontinuation of study treatment(s) | From enrollment until 30 days after completion of study treatment | Phase 1 |
| Overall response rate (ORR) | Up to approximately 43 months | Phase 2 only according to RECIST v1.1 criteria |
| Disease control rate (DCR) at 3, 6, and 12 months | Up to 12 months | Phase 2 |
| Duration of Response (DOR) | Up to approximately 43 months | Phase 2 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | Up to approximately 43 months | Phase 1 and Phase 2 |
| Frequency and severity of AEs and SAEs | From enrollment until 30 days after completion of study treatment | Phase 2 |
| Assess the pharmacodynamics by percent reduction from baseline of target protein | At multiple time points up to 4 weeks | Tumor BRAF-V600 degradation at scheduled timepoints |
| Duration of response (DOR) | Up to approximately 43 months | Phase 1 |
| 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 | Phase 2 |
| Frequency of dose interruptions and dose reductions | From enrollment until 30 days after completion of study treatment | Phase 2 |
| Frequency of AEs leading to discontinuation of study treatment(s) | From enrollment until 30 days after completion of study treatment | Phase 2 |
| Plasma concentration of CFT1946 to characterize the pharmacokinetics (PK) parameters of CFT1946 monotherapy and in combination with trametinib | Up to approximately 20 weeks | Phase 1 and Phase 2 |
| PK-QTcF relationship | Up to approximately 8 weeks | Phase 1 and Phase 2 |
| Overall response rate (ORR) | Up to approximately 43 months | Phase 1 |
| Disease control rate (DCR) at 3, 6, and 12 months | Up to 12 months | Phase 1 |
Countries
France, Germany, Spain, United Kingdom, United States
Outcome results
None listed