A Study of BDTX-4933 in Patients With KRAS, BRAF and Select RAS/MAPK Mutation-Positive Cancers
Launched by INSTITUT DE RECHERCHES INTERNATIONALES SERVIER · Mar 15, 2023
Trial Information
Current as of July 22, 2025
Recruiting
Keywords
ClinConnect Summary
This clinical trial is studying a new medication called BDTX-4933, which is being tested in patients with certain types of advanced cancers that have specific genetic mutations, like those found in KRAS or BRAF genes. The trial aims to find out how safe the medication is, how much of it can be given, and whether it helps shrink tumors in patients with conditions such as non-small cell lung cancer, melanoma, and other solid tumors. Participants will take this medication by mouth in cycles lasting 28 days until their disease worsens, they experience too many side effects, or they decide to leave the study.
To be eligible for this trial, patients need to have advanced or recurrent cancers that are confirmed by tests to have specific mutations. They should have already tried standard treatments without success or may not be able to tolerate them. Participants must also have stable organ function and be expected to live for at least 12 weeks. During the trial, patients will be closely monitored for any side effects or changes in their condition. It's also important to know that certain health issues, like active infections or recent surgeries, may prevent someone from joining the study.
Gender
ALL
Eligibility criteria
- Key Inclusion Criteria:
- 1. Disease criteria:
- • 1. Histologically or cytologically confirmed recurrent/advanced (unresectable) or metastatic solid tumors or histiocytic neoplasms with documented RAS or BRAF mutations.
- • Note: Patients may have stable central nervous system (CNS) metastases. Patients with active CNS metastases or primary CNS tumors associated with progressive neurological symptoms or needing increased doses of corticosteroids to control the CNS disease are excluded from the study.
- 2. Dose Escalation cohorts:
- • NSCLC with KRAS non-G12C mutations, including other mutations at KRAS-G12 (eg, G12V/G12D) and other oncogenic variants of KRAS mutations on G13 and Q61 amino acid residues, BRAF, or CRAF mutations.
- • Melanoma with BRAF, CRAF, or NRAS mutations.
- • Histiocytic neoplasms with BRAF or NRAS mutations.
- • Thyroid carcinoma with BRAF mutations.
- • Colorectal carcinoma with BRAF (Class II or III) mutations with Sponsor approval.
- • Other solid tumors with BRAF Class I mutations after prior treatment with a BRAF/MEK inhibitor or local standard-of-care with Sponsor approval.
- 3. Dose Expansion cohort:
- • Recurrent advanced/metastatic NSCLC with KRAS non-G12C mutations without small cell lung cancer transformation with progressive disease confirmed by radiographic assessment.
- • 2. Prior standard-of-care
- For dose levels \<200 mg once daily and/or not at preliminary RP2D(s):
- • 1. Exhausted all available standard-of-care therapies or, in the opinion of the Investigator, would be unlikely to tolerate or derive clinically meaningful benefit from available standard-of-care therapy.
- • 2. Patients with eligible tumors harboring BRAF V600E mutations must have received FDA approved BRAF targeted therapy, BRAF/MEK inhibitors combination, or BRAF inhibitors combination.
- For dose levels ≥200 mg once daily or at preliminary RP2D(s):
- • a. Patients must have received at least 1 but no more than 2 prior lines of systemic therapy for metastatic/advanced disease (adjuvant and maintenance therapy do not count towards the limit).
- • 3. Evaluable or measurable disease in dose escalation and measurable disease only for dose expansion cohorts.
- • 4. Adequate bone marrow and organ function.
- • 5. Recovered from toxicity to prior anti-cancer therapy.
- • 6. Appropriate candidate for BDTX-4933 monotherapy.
- • 7. Life expectancy of \>=12 weeks in the opinion of the Investigator.
- Key Exclusion Criteria:
- • 1. Cancer that has a known MEK1/2 mutation.
- • 2. Major surgery within 4 weeks of study entry or planned during study.
- • 3. Ongoing anticancer therapy.
- • 4. Ongoing radiation therapy.
- • 5. Uncontrolled or active clinically relevant bacterial, fungal, or specific viral infection requiring systemic therapy.
- • 6. Symptomatic spinal cord compression.
- • 7. Evidence of active malignancy (other than study-specific malignancies) requiring systemic therapy within the next 2 years.
- • 8. History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
- • 9. Females who are pregnant or breastfeeding.
- • 10. Actively receiving systemic treatment or direct medical intervention on another therapeutic clinical study.
- • 11. Prior use of experimental agents that target the KRAS/BRAF/MEK/ERK pathway.
About Institut De Recherches Internationales Servier
Institut de Recherches Internationales Servier is a leading independent international pharmaceutical company based in France, dedicated to advancing medical research and developing innovative therapeutic solutions. With a strong focus on areas such as cardiology, diabetes, oncology, and neuropsychiatry, Servier is committed to improving patient outcomes through rigorous clinical trials and collaboration with healthcare professionals worldwide. The organization emphasizes a patient-centric approach and invests significantly in research and development, striving to address unmet medical needs and enhance the quality of life for patients globally.
Contacts
Jennifer Cobb
Immunology at National Institute of Allergy and Infectious Diseases (NIAID)
Locations
Seattle, Washington, United States
New York, New York, United States
Tampa, Florida, United States
Boston, Massachusetts, United States
Los Angeles, California, United States
Minneapolis, Minnesota, United States
Washington, District Of Columbia, United States
Saint Louis, Missouri, United States
Chapel Hill, North Carolina, United States
Aurora, Colorado, United States
Gilbert, Arizona, United States
Fairfax, Virginia, United States
Grand Rapids, Michigan, United States
Grand Rapids, Michigan, United States
Fairfax, Virginia, United States
Salt Lake City, Utah, United States
Patients applied
Timeline
First submit
Trial launched
Trial updated
Estimated completion
Not reported
Similar Trials