BDTX-4933 for Cancer

Recruiting at 17 trial locations

Overseen By Institut de Recherches Internationales Servier (I.R.I.S.), Clinical Studies Department

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Institut de Recherches Internationales Servier

Must not be taking: Anticancer, Radiation, Experimental agents

Disqualifiers: MEK1/2 mutation, Major surgery, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

554 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called BDTX-4933 to determine its safety and effectiveness for individuals with specific types of advanced cancers. It targets patients with non-small cell lung cancer, melanoma, histiocytic neoplasms, and other solid tumors, particularly those with certain gene mutations like KRAS, BRAF, or NRAS. Participants should have previously tried other treatments without success and have a type of cancer that meets the study criteria. The trial aims to identify the optimal dose of BDTX-4933 and evaluate its effectiveness against tumors. Participants will take the medication orally in cycles until they can no longer continue for various reasons. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, ongoing anticancer therapy and radiation therapy are not allowed during the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that BDTX-4933 is still under investigation to determine its safety for people. In earlier studies, researchers examined how well participants tolerated this treatment and identified any short-term side effects. They continue to gather information to better understand its safety.

Since this trial is in its early stages, researchers are carefully determining the right dose and monitoring for any side effects. Although specific safety results are not yet available, early-stage trials like this one are designed to ensure safety before proceeding further.

Prospective participants should know that researchers are focused on understanding how well people tolerate BDTX-4933 and identifying potential side effects. This process helps ensure the treatment is as safe as possible for participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about BDTX-4933 because it represents a new approach to cancer treatment. Unlike typical cancer therapies that target specific proteins or pathways, BDTX-4933 is designed to inhibit a broad range of cancer-driving mutations, potentially making it effective against various tumor types. This versatility could provide a more personalized treatment option for patients whose cancers have not responded to existing therapies. Additionally, by targeting these mutations directly, BDTX-4933 may reduce the likelihood of cancer cells developing resistance, offering a longer-lasting response.

What evidence suggests that this trial's treatments could be effective for cancer?

Research shows that BDTX-4933, the investigational treatment in this trial, may help treat cancers with certain genetic changes. Early studies found that it can slow tumor growth in cases with BRAF mutations, particularly in the brain. This drug blocks specific pathways in cancer cells, which can stop them from growing. In this trial, BDTX-4933 will be tested both as a monotherapy and in combination with other treatments. When combined with other treatments, targeting the MAPK pathway has yielded better results in hard-to-treat cancers like colorectal cancer. These findings suggest that BDTX-4933 could be effective for patients whose tumors have specific genetic profiles. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

Adults with recurrent advanced/metastatic cancers that have specific mutations in the BRAF, KRAS (excluding G12C), or NRAS genes. This includes certain types of lung cancer, melanoma, thyroid cancer, colorectal cancer and other solid tumors. Participants must have tried standard treatments without success and should not be pregnant or breastfeeding.

Inclusion Criteria

My cancer is advanced, cannot be surgically removed, and has RAS or BRAF mutations.

Specific criteria for Dose Escalation cohorts: NSCLC with KRAS non-G12C mutations, Melanoma with BRAF or NRAS mutations, Histiocytic neoplasms with BRAF or NRAS mutations, Thyroid carcinoma with BRAF mutations, Colorectal carcinoma with BRAF mutations, Other solid tumors with BRAF mutations after prior treatment with a BRAF/MEK inhibitor, Specific criteria for 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

My brain metastases are stable and I don't need more steroids for them.

Exclusion Criteria

Cancer with a known MEK1/2 mutation, 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, Symptomatic spinal cord compression, Evidence of active malignancy 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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

BDTX-4933 is administered at escalating dose levels to determine the maximum tolerated dose (MTD) and preliminary recommended Phase 2 dose (RP2D)

28-day cycles

Cycle 1 includes monitoring for dose-limiting toxicities

Dose Expansion

BDTX-4933 is administered at the RP2D to further evaluate safety and antitumor activity

28-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BDTX-4933

Trial Overview BDTX-4933 is being tested for its safety and effectiveness against various cancers with specific genetic mutations. Patients will take this oral medication in cycles of 28 days to see if it can control their cancer growth.

How Is the Trial Designed?

Group I: Part 2F: Exploratory Food Effect Experimental Treatment 1 Intervention

S241656 will be administered as a monotherapy.

Group II: Part 2D1: Dose Expansion CRC Experimental Treatment 1 Intervention

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.

Group III: Part 2C1: Dose Expansion PDAC Experimental Treatment 1 Intervention

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.

Group IV: Part 2B3: Dose Expansion BTC Experimental Treatment 1 Intervention

S241656 will be administered as a monotherapy in the BED range.

Group V: Part 2B2: Dose Expansion CRC Experimental Treatment 1 Intervention

S241656 will be administered as a monotherapy in the BED range.

Group VI: Part 2B1: Dose Expansion PDAC Experimental Treatment 1 Intervention

S241656 will be administered as a monotherapy in the BED range.

Group VII: Part 2A: Dose Optimization NSCLC Experimental Treatment 1 Intervention

S241656 will be administered to further characterize the optimal dose.

Group VIII: Part 2A4: Dose Expansion NSCLC with a KRAS G12C mutation Experimental Treatment 1 Intervention

S241656 will be administered as a monotherapy in the BED range. Participants must have received and progressed upon G12C targeted therapy

Group IX: Part 2A3: Dose Expansion NSCLC with KRAS non-G12C or BRAF mutations/alterations Experimental Treatment 1 Intervention

S241656 will be administered as a monotherapy in the BED range. Participants must also have active CNS metastatic disease

Group X: Part 2A2: Dose Expansion NSCLC with BRAF mutations Experimental Treatment 1 Intervention

S241656 will be administered as a monotherapy in the BED range.

Group XI: Part 2A1: Dose Expansion NSCLC with KRAS non-G12C mutations Experimental Treatment 1 Intervention

S241656 will be administered as a monotherapy in the BED range.

Group XII: Part 1E: Dose Escalation Other Solid Tumors Experimental Treatment 1 Intervention

S241656 will be administered as a monotherapy at escalating dose levels until the BED range is determined.

Group XIII: Part 1D: Dose Escalation CRC Experimental Treatment 5 Interventions

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.

Group XIV: Part 1C: Dose Escalation PDAC Experimental Treatment 3 Interventions

S241656 will be administered in combination with gemcitabine/nab-paclitaxel at escalating dose levels until the BED range is determined.

Group XV: Part 1B: Dose Escalation GI Tumors Experimental Treatment 1 Intervention

S241656 will be administered as a monotherapy at escalating dose levels until the BED range is determined.

Group XVI: Part 1A: Dose Escalation NSCLC Experimental Treatment 1 Intervention

S241656 will be administered as a monotherapy at escalating dose levels until the biologically effective dose (BED) range is determined.

Who Is Running the Clinical Trial?

Institut de Recherches Internationales Servier

Lead Sponsor

Trials

91

Recruited

67,100+

Black Diamond Therapeutics, Inc.

Lead Sponsor

Trials

3

Recruited

390+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05786924

A Study of BDTX-4933 in Patients With KRAS, BRAF and ... BDTX-4933-101 is a first-in-human, open-label, Phase 1 dose escalation and an expansion cohort study designed to evaluate the safety and tolerability, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11283586/

mutant colorectal cancer - PMC - PubMed Central - NIH The results of the BEACON CRC trial fully confirmed the superior efficacy of targeted therapy against the MAPK pathway. ... BDTX‐4933 (Pan‐RAF ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S221138352400056X

REVIEW Targeting RAF dimers in RAS mutant tumors This review aims to clarify the importance of RAF dimerization in cellular signaling and resistance to treatment in tumors with RAS mutations.

4. ascopubs.org ascopubs.org/doi/10.1200/OP.24.00295

Setting Off on the Mission to Target KRAS in Colorectal ... A sequential blockade of the RAS-MAPK pathway is generally viewed as a more promising means of targeting KRAS G12C mutations than monotherapy.

5. actr.amegroups.org actr.amegroups.org/article/download/11457/12054

Encorafenib, cetuximab and chemotherapy: a mole against BRAF ... The identification of key oncogenic drivers and the subsequent development of targeted therapies have significantly improved clinical outcomes of patients ...

6. cancer.gov cancer.gov/clinicaltrials/NCI-2023-03966

A Study of BDTX-4933 in Patients With KRAS, BRAF and ... BDTX-4933-101 is a first-in-human, open-label, Phase 1 dose escalation and an expansion cohort study designed to evaluate the safety and tolerability.

7. investors.blackdiamondtherapeutics.com investors.blackdiamondtherapeutics.com/news-releases/news-release-details/black-diamond-therapeutics-announces-initial-phase-2-data

Black Diamond Therapeutics Announces Initial Phase 2 ... BDTX-1535 dose of 200 mg daily selected for pivotal development; favorable tolerability profile and no new safety signals observed.

8. servier.com servier.com/en/newsroom/servier-black-diamond-therapeutics-announce-global-licensing-agreement-bdtx-4933-targeted-oncology-therapy/

Servier and Black Diamond Therapeutics Announce Global ... Our partnership to develop BDTX-4933 is an important opportunity in targeted cancer therapies, as we believe we can serve more people by helping ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT05786924?cond=(LUNG%20CANCER)%20OR%20(BRAF%20OR%20ERBB2%20OR%20PPP2R1B%20OR%20PIK3CA%20OR%20ERCC6%20OR%20CYP2A6%20OR%20SLC22A1L%20OR%20PRKN%20OR%20FASLG%20OR%20KRAS%20OR%20CASP8%20OR%20EGFR%20OR%20IRF1%20OR%20MAP3K8)&rank=8

A Study of BDTX-4933 in Patients With KRAS, BRAF and ... Safety continues to be evaluated, and short-term adverse events are studied. ... A phase of research to describe clinical trials that gather more information ...