S241656 as Monotherapy and in Combination With Other Anti-Cancer Therapies

What is the Purpose of this Study?

The purpose of this study is to evaluate an experimental drug called S241656 in people who have cancer with a mutation in the KRAS, NRAS, HRAS, BRAF, and/or CRAF (RAF1) genes in their tumor. S241656 is a type of anti-cancer drug designed to target and block cancers with certain types of gene mutations and other genetic alterations in the tumor that help them survive and grow. The study is divided into 2 parts. In Part 1, groups of participants will receive different doses and/or dose schedules (once daily or twice daily) of S241656 alone or in combination with other therapies to determine the best and safest dose. In Part 2, the study will evaluate the best dose observed in Part 1 in a larger number of participants receiving an identical dose and schedule of study drug(s) to better determine the safety and effectiveness of S241656 alone or in combination with other therapies. Participants will be included in Part 1 or Part 2 depending on which part of the study is active at the time of enrollment.

Eligibility

* Life expectancy of ≥ 12 weeks in the opinion of the investigator.
* Histologically or cytologically confirmed recurrent locally advanced (unresectable) or metastatic solid tumors with documented RAS or RAF mutations or alterations.
* Adequate bone marrow and organ function.
* Recovered from toxicity to prior anti-cancer therapy.

Key Inclusion Criteria:

* Life expectancy of ≥ 12 weeks in the opinion of the investigator.
* Histologically or cytologically confirmed recurrent locally advanced (unresectable) or metastatic solid tumors with documented RAS or RAF mutations or alterations.
* Adequate bone marrow and organ function.
* Recovered from toxicity to prior anti-cancer therapy.
Part 1 Dose Escalation cohort ONLY:
* Part 1A: Advanced/metastatic NSCLC with KRAS non-G12C, HRAS, NRAS, BRAF or CRAF (RAF1) mutations or alterations
* Part 1B: Advanced/metastatic GI tumors (e.g., PDAC, CRC, and BTC) with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations or alterations
* Part 1C: Advanced/metastatic PDAC with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations or alterations
* Part 1D: Colorectal adenocarcinoma with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations or alterations
* Part 1E: Other advanced/metastatic non-GI, non-NSCLC solid tumors with KRAS, HRAS, NRAS, BRAF, CRAF (RAF1) mutations or alterations
Part 2 Dose Optimization and Expansion cohorts ONLY:
* Part 2A: Advanced/metastatic NSCLC with KRAS non-G12C mutations and/or BRAF mutations
* Part 2A1: Advanced/metastatic NSCLC with KRAS non-G12C mutations
* Part 2A2: Advanced/metastatic NSCLC with BRAF mutations
* Part 2A3: Advanced/metastatic NSCLC with KRAS non-G12C or BRAF mutations or alterations and active CNS metastatic disease
* Part 2A4: Advanced/metastatic NSCLC with a KRAS G12C mutation
* Part 2B1: Advanced/metastatic PDAC with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations or alterations
* Part 2B2: Advanced/metastatic CRC with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations or alterations
* Part 2B3: Advanced/metastatic BTC (adenocarcinoma) with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations or alterations

Key Exclusion Criteria:

* Cancer that has a known MEK1/2 mutation.
* Known allergy/hypersensitivity to excipients of S241656 or to any of the registered IMPs administered in combination.
* Any contra-indication, to use of any of the combination chemotherapy or anti-EGFR therapy partners administered as part of this trial.
* Major surgery within 4 weeks of study entry or planned during study.
* Ongoing anticancer therapy.
* Ongoing radiation therapy.
* Uncontrolled or active clinically relevant bacterial, fungal, or specific viral infection requiring systemic therapy.
* Clinically significant cardiovascular disease.
* Symptomatic spinal cord compression.
* Evidence of active malignancy (other than study-specific malignancies) requiring systemic therapy within the next 2 years.
* History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
* Females who are pregnant or breastfeeding.
* Actively receiving systemic treatment or direct medical intervention on another therapeutic clinical study.
* Prior use of experimental agents that target the KRAS/BRAF/MEK/ERK pathway.

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Where can I participate?

CS Cancer at The Angeles Clinic and Research Institute : Saba Mukarram

More about this Clinical Trial

What is the full name of this clinical trial?

BDTX-4933-101: A Phase 1/2, Open-label Study of Oral S241656 as Monotherapy and in Combination with Other Anti-Cancer Therapies in Patients with KRAS, BRAF and Other Selected RAS/MAPK Mutation-Positive Malignancies

Study Details

Disease Type/Condition

Anus, Bones and Joints, Brain and Nervous System, Breast, Cervix, Colon, Esophagus, Eye and Orbit, Hodgkin Lymphoma, Kaposi's Sarcoma, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung, Melanoma, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Hematopoietic, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Soft Tissue, Stomach, Thyroid, Urinary Bladder

Principal Investigator

Grussie, Erwin

Co-Investigators

Cathie T Chung, Inderjit Mehmi, Iryna Singh, Kristopher Wentzel, Omid Hamid

Age Group

Adult

Phase

I/II

IRB Number

STUDY00004697

ClinicalTrials.gov ID

NCT05786924