RECRUITING

Phase 1/2 Trial of S241656 in Selected RAS/MAPK Mutation- Positive Malignancies

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

BDTX-4933-101 is a first-in-human, open-label, Phase 1/2 dose escalation, dose optimization and expansion study designed to evaluate the safety and tolerability of S241656 as monotherapy and in combination with other anti-cancer therapies in participants with selected advanced malignancies. The study population for the Dose Escalation part of the study comprises adults with recurrent advanced/metastatic non-small cell lung cancer (NSCLC), Gastrointestinal (GI) cancers, and other solid tumors harboring KRAS, HRAS, NRAS, BRAF, and/or CRAF (Rapidly Accelerated Fibrosarcoma (RAF1)) mutations or alterations. A dose optimization part in adults with NSCLC may follow the dose escalation phase if the sponsor, in consultation with the safety review committee, decides it is necessary to further characterize the optimal dose. However, the study may also proceed directly to the expansion phase. The study population for the Dose Expansion part of the study comprises adults with advanced/metastatic NSCLC with KRAS and/or BRAF mutations, and with Pancreatic Ductal AdenoCarcinoma (PDAC), ColoRectal Cancer (CRC), and Biliary Tract Cancer (BTC) with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations and alterations. All patients will self-administer S241656 orally in 28-day cycles until disease progression, toxicity, withdrawal of consent, or termination of the study.

Official Title

A Phase 1/2, Open-label Study of Oral S241656 (BDTX-4933) as Monotherapy and in Combination With Other Anti-Cancer Therapies in Patients With KRAS, BRAF and Other Selected RAS/MAPK Mutation-Positive Malignancies

Quick Facts

Study Start:2023-04-18
Study Completion:2028-06
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT05786924

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * Life expectancy of ≥ 12 weeks in the opinion of the investigator.
  2. * Histologically or cytologically confirmed recurrent locally advanced (unresectable) or metastatic solid tumors with documented RAS or RAF mutations or alterations.
  3. * Adequate bone marrow and organ function.
  4. * Recovered from toxicity to prior anti-cancer therapy.
  5. * Part 1A: Advanced/metastatic NSCLC with KRAS non-G12C, HRAS, NRAS, BRAF or CRAF (RAF1) mutations or alterations
  6. * Part 1B: Advanced/metastatic GI tumors (e.g., PDAC, CRC, and BTC) with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations or alterations
  7. * Part 1C: Advanced/metastatic PDAC with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations or alterations
  8. * Part 1D: Colorectal adenocarcinoma with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations or alterations
  9. * Part 1E: Other advanced/metastatic non-GI, non-NSCLC solid tumors with KRAS, HRAS, NRAS, BRAF, CRAF (RAF1) mutations or alterations
  10. * Part 2A: Advanced/metastatic NSCLC with KRAS non-G12C mutations and/or BRAF mutations
  11. * Part 2A1: Advanced/metastatic NSCLC with KRAS non-G12C mutations
  12. * Part 2A2: Advanced/metastatic NSCLC with BRAF mutations
  13. * Part 2A3: Advanced/metastatic NSCLC with KRAS non-G12C or BRAF mutations or alterations and active CNS metastatic disease
  14. * Part 2A4: Advanced/metastatic NSCLC with a KRAS G12C mutation
  15. * Part 2B1: Advanced/metastatic PDAC with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations or alterations
  16. * Part 2B2: Advanced/metastatic CRC with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations or alterations
  17. * Part 2B3: Advanced/metastatic BTC (adenocarcinoma) with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations or alterations
  1. * Cancer that has a known MEK1/2 mutation.
  2. * Known allergy/hypersensitivity to excipients of S241656 or to any of the registered IMPs administered in combination.
  3. * Any contra-indication, to use of any of the combination chemotherapy or anti-EGFR therapy partners administered as part of this trial.
  4. * Major surgery within 4 weeks of study entry or planned during study.
  5. * Ongoing anticancer therapy.
  6. * Ongoing radiation therapy.
  7. * Uncontrolled or active clinically relevant bacterial, fungal, or specific viral infection requiring systemic therapy.
  8. * Clinically significant cardiovascular disease.
  9. * Symptomatic spinal cord compression.
  10. * Evidence of active malignancy (other than study-specific malignancies) requiring systemic therapy within the next 2 years.
  11. * History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
  12. * Females who are pregnant or breastfeeding.
  13. * Actively receiving systemic treatment or direct medical intervention on another therapeutic clinical study.
  14. * Prior use of experimental agents that target the KRAS/BRAF/MEK/ERK pathway.

Contacts and Locations

Study Contact

Institut de Recherches Internationales Servier (I.R.I.S.), Clinical Studies Department
CONTACT
+33 1 55 72 60 00
scientificinformation@servier.com

Study Locations (Sites)

Banner Health- MD Anderson Cancer Center
Gilbert, Arizona, 85234
United States
University of Colorado - Aurora Cancer Center
Aurora, Colorado, 80045
United States
Georgetown University Lombardi Cancer Center
Washington D.C., District of Columbia, 20007
United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
United States
South Texas Accelerated Research Therapeutics (START) Midwest
Grand Rapids, Michigan, 49546
United States
Masonic Cancer Center University of Minnesota
Minneapolis, Minnesota, 55455
United States
Washington University
St Louis, Missouri, 63130
United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
United States
NEXT Virginia
Fairfax, Virginia, 22031
United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
United States

Collaborators and Investigators

Sponsor: Institut de Recherches Internationales Servier

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-04-18
Study Completion Date2028-06

Study Record Updates

Study Start Date2023-04-18
Study Completion Date2028-06

Terms related to this study

Keywords Provided by Researchers

  • BRAF Class I
  • BRAF Class II
  • BRAF Class III
  • KRAS
  • Intolerant histiocytic neoplasm
  • BDTX-4933
  • Phase 1
  • dose escalation
  • dose expansion
  • MAPK
  • mitogen-activated protein kinase
  • RAS
  • RAF
  • Upstream oncogenic alterations
  • RAF inhibitor
  • intracranial disease
  • CRAF
  • NRAS
  • RAF fusions

Additional Relevant MeSH Terms

  • Non-small Cell Lung Cancer
  • Histiocytic Neoplasm
  • Histiocytosis
  • BRAF Gene Mutation
  • BRAF V600E
  • BRAF V600 Mutation
  • BRAF Mutation-Related Tumors
  • BRAF
  • Metastatic Lung Non-Small Cell Carcinoma
  • Metastatic Lung Cancer
  • Recurrent Lung Cancer
  • Recurrent Lung Non-Small Cell Carcinoma
  • NSCLC
  • Solid Tumor
  • Solid Carcinoma
  • KRAS G12D
  • KRAS G12V
  • KRAS Mutation-Related Tumors
  • NRAS Gene Mutation
  • Thyroid Cancer
  • Thyroid Carcinoma
  • Colorectal Cancer
  • Colorectal Carcinoma
  • Recurrent Histiocytic and Dendritic Cell Neoplasm
  • Brain Metastases
  • Recurrent NSCLC
  • KRAS G13C
  • Acquired Resistance to KRAS G12C Inhibitor
  • KRAS G12A
  • KRAS G12F
  • KRAS G12R
  • KRAS G13D