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| ID | Type | Description | Link |
|---|---|---|---|
| 2025-523474-16-00 | EU Trial (CTIS) Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1A: Dose Escalation NSCLC | Experimental | S241656 will be administered as a monotherapy at escalating dose levels until the biologically effective dose (BED) range is determined. |
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| Part 1B: Dose Escalation GI Tumors | Experimental | S241656 will be administered as a monotherapy at escalating dose levels until the BED range is determined. |
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| Part 1C: Dose Escalation PDAC | Experimental | S241656 will be administered in combination with gemcitabine/nab-paclitaxel at escalating dose levels until the BED range is determined. |
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| Part 1D: Dose Escalation CRC | Experimental | S241656 will be administered in combination with FOLFOX6/FOLFOX7 or FOLFIRI, and panitumumab or cetuximab at escalating dose levels until the BED range is determined. |
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| Part 1E: Dose Escalation Other Solid Tumors | Experimental | S241656 will be administered as a monotherapy at escalating dose levels until the BED range is determined. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| S241656 | Drug | RAF inhibitor targeting all classes of oncogenic BRAF alterations (Classes I, II, and III) and constitutively active CRAF, KRAS or NRAS mutations |
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| Measure | Description | Time Frame |
|---|---|---|
| Dose Escalation: Incidence of dose-limiting toxicities (DLTs) | A DLT is defined as any event meeting the DLT criteria occurring within the first 28-day cycle | The first 28-day cycle (Cycle 1) |
| Dose Escalation: Number of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Through study completion, approximately 5 years | |
| Dose Optimization/Expansion: Objective response (OR) | Through study completion, approximately 5 years |
| Measure | Description | Time Frame |
|---|---|---|
| Dose Escalation/Expansion: Incidence and severity of treatment-emergent adverse events (TEAEs) | Through study completion, approximately 5 years | |
| Dose Escalation/Optimization/Expansion: Maximum plasma concentration (Cmax) of S241656 and its metabolite S243796 |
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Key Inclusion Criteria:
Part 1 Dose Escalation cohort ONLY:
Part 2 Dose Optimization and Expansion cohorts ONLY:
Key Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Institut de Recherches Internationales Servier (I.R.I.S.), Clinical Studies Department | Contact | +33 1 55 72 60 00 | scientificinformation@servier.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Banner Health- MD Anderson Cancer Center | Recruiting | Gilbert | Arizona | 85234 | United States |
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| Part 2A: Dose Optimization NSCLC | Experimental | S241656 will be administered to further characterize the optimal dose. |
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| Part 2A1: Dose Expansion NSCLC with KRAS non-G12C mutations | Experimental | S241656 will be administered as a monotherapy in the BED range. |
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| Part 2A2: Dose Expansion NSCLC with BRAF mutations | Experimental | S241656 will be administered as a monotherapy in the BED range. |
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| Part 2A3: Dose Expansion NSCLC with KRAS non-G12C or BRAF mutations/alterations | Experimental | S241656 will be administered as a monotherapy in the BED range. Participants must also have active CNS metastatic disease |
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| Part 2A4: Dose Expansion NSCLC with a KRAS G12C mutation | Experimental | S241656 will be administered as a monotherapy in the BED range. Participants must have received and progressed upon G12C targeted therapy |
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| Part 2B1: Dose Expansion PDAC | Experimental | S241656 will be administered as a monotherapy in the BED range. |
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| Part 2B2: Dose Expansion CRC | Experimental | S241656 will be administered as a monotherapy in the BED range. |
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| Part 2B3: Dose Expansion BTC | Experimental | S241656 will be administered as a monotherapy in the BED range. |
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| Part 2C1: Dose Expansion PDAC | Experimental | S241656 will be administered in combination with anti-cancer therapies in the BED range. The combination therapies to be used will be determined in the future. |
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| Part 2D1: Dose Expansion CRC | Experimental | S241656 will be administered in combination with anti-cancer therapies in the BED range. The combination therapies to be used will be determined in the future. |
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| Part 2F: Exploratory Food Effect | Experimental | S241656 will be administered as a monotherapy. |
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| FOLFOX6/FOLFOX7 | Drug | Used as a combination therapy and administered intravenously |
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| FOLFIRI | Drug | Used as a combination therapy and administered intravenously |
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| Cetuximab | Drug | Used as a combination therapy and administered intravenously |
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| Panitumumab | Drug | Used as a combination therapy and administered intravenously |
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| Gemcitabine | Drug | Used as a combination therapy and administered intravenously |
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| Nab-paclitaxel | Drug | Used as a combination therapy and administered intravenously |
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| Through study completion, approximately 5 years |
| Dose Escalation/Optimization/Expansion: Time of maximum plasma concentration (Tmax) of S241656 and its metabolite S243796 | Through study completion, approximately 5 years |
| Dose Escalation/Optimization/Expansion: Area under the plasma drug concentration-time curve (AUC) of S241656 and its metabolite S243796 | Through study completion, approximately 5 years |
| Dose Escalation/Optimization/Expansion: Half-life (t1/2) of S241656 and its metabolite S243796 | Through study completion, approximately 5 years |
| Dose Escalation: Objective response (OR) | Through study completion, approximately 5 years |
| Dose Escalation/Optimization/Expansion: Disease Control (DC) | Through study completion, approximately 5 years |
| Dose Escalation/Optimization/Expansion: Clinical Benefit (CB) | Through study completion, approximately 5 years |
| Dose Escalation/Optimization/Expansion: Duration of response (DOR) | Through study completion, approximately 5 years |
| Dose Escalation/Optimization/Expansion: Time to response (TTR) | Through study completion, approximately 5 years |
| Dose Escalation/Optimization/Expansion: Progression-free Survival (PFS) | Through study completion, approximately 5 years |
| Dose Escalation/Optimization/Expansion: Overall survival (OS) | Through study completion, approximately 5 years |
| Dose Optimization/Expansion: Number of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Through study completion, approximately 5 years |
| Dose Escalation/Optimization/Expansion: Number of Dose Interruptions | Through study completion, approximately 5 years |
| Dose Escalation/Optimization/Expansion: Number of Dose Reductions | Through study completion, approximately 5 years |
| Dose Escalation: Number of Dose Discontinuations | Through study completion, approximately 5 years |
| Dose Optimization/Expansion: Changes in allelic fraction of DNA sequence variants detected in ctDNA from baseline to on-treatment time points | Through study completion, approximately 5 years |
| The Angeles clinic - A cedars SINAI AFFILIATE | Recruiting | Los Angeles | California | 90025 | United States |
| USC Norris Comprehensive Cancer Center | Recruiting | Los Angeles | California | 90033 | United States |
| University of California, San Francisco (UCSF) | Recruiting | San Francisco | California | 94143 | United States |
| University of Colorado - Aurora Cancer Center | Not yet recruiting | Aurora | Colorado | 80045 | United States |
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| Yale University School of Medicine - Yale Cancer Center | Recruiting | New Haven | Connecticut | 06520-8028 | United States |
| Georgetown University Lombardi Cancer Center | Not yet recruiting | Washington D.C. | District of Columbia | 20007 | United States |
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| Dana-Farber Cancer Institute | Recruiting | Boston | Massachusetts | 02215 | United States |
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| South Texas Accelerated Research Therapeutics (START) Midwest | Recruiting | Grand Rapids | Michigan | 49546 | United States |
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| Masonic Cancer Center University of Minnesota | Recruiting | Minneapolis | Minnesota | 55455 | United States |
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| Washington University | Recruiting | St Louis | Missouri | 63130 | United States |
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| NYU Langone Medical Center - Perlmutter Cancer Center (NYU Cancer Institute) | Recruiting | New York | New York | 10016 | United States |
| Memorial Sloan Kettering Cancer Center | Recruiting | New York | New York | 10065 | United States |
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| Duke University School of Medicine | Recruiting | Durham | North Carolina | 27710 | United States |
| Cleveland Clinic | Recruiting | Cleveland | Ohio | 44195 | United States |
| Sarah Canon Research Institute (SCRI) Oncology Partners | Recruiting | Nashville | Tennessee | 37203 | United States |
| MD Anderson Cancer Center | Recruiting | Houston | Texas | 77030 | United States |
| START San Antonio | Recruiting | San Antonio | Texas | 78229 | United States |
| NEXT Virginia | Recruiting | Fairfax | Virginia | 22031 | United States |
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| Fred Hutchinson Cancer Research Center | Recruiting | Seattle | Washington | 98109 | United States |
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| Center for Cancer and Organ Diseases - Rigshospitalet | Recruiting | Copenhagen | 2100 | Denmark |
| Queen Mary Hospital | Recruiting | Hong Kong | Hong Kong |
| Kyoto University Hospital | Recruiting | Kyoto | 606-8507 | Japan |
| National Cancer Center Hospital | Recruiting | Tokyo | 104-0045 | Japan |
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| University College London Hospital | Recruiting | London | NW1 2PG | United Kingdom |
| Hammersmith Hospital | Recruiting | London | W12 0HS | United Kingdom |
| The Christie NHS Foundation Trust | Recruiting | Manchester | M20 4BX | United Kingdom |
| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| D015614 | Histiocytosis |
| D008175 | Lung Neoplasms |
| D013964 | Thyroid Neoplasms |
| D015179 | Colorectal Neoplasms |
| D001932 | Brain Neoplasms |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D004701 | Endocrine Gland Neoplasms |
| D006258 | Head and Neck Neoplasms |
| D004700 | Endocrine System Diseases |
| D013959 | Thyroid Diseases |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| C480833 | IFL protocol |
| D000068818 | Cetuximab |
| D000077544 | Panitumumab |
| D000093542 | Gemcitabine |
| C520255 | 130-nm albumin-bound paclitaxel |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D006571 | Heterocyclic Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
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