Daraxonrasib for Non-Small Cell Lung Cancer

(RASolve 301 Trial)

Recruiting at 98 trial locations

Overseen By Revolution Medicines Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Revolution Medicines, Inc.

Must not be taking: Direct RAS-targeted, Docetaxel

Disqualifiers: CNS metastases, Cardiovascular, Lung, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 4 years

420 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, daraxonrasib, for individuals with non-small cell lung cancer (NSCLC) to determine its safety and effectiveness compared to the standard treatment, docetaxel. It targets those whose cancer cannot be cured by surgery or radiation and who have a specific RAS mutation (a change in the cancer cell's DNA). Participants should have previously undergone one or two cancer treatments, including a specific type of chemotherapy and immunotherapy. This trial offers a new approach for those whose previous treatments have been unsuccessful. As a Phase 3 trial, it represents the final step before FDA approval, providing a promising new option for patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but ongoing anticancer therapy is not allowed.

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

Research has shown that daraxonrasib, a new treatment being tested for non-small cell lung cancer (NSCLC), has a manageable safety profile based on earlier studies. Most side effects were expected and could be controlled. Patients with previously treated NSCLC who took daraxonrasib experienced some side effects, but these were generally mild to moderate.

Although specific data from these studies aren't provided here, daraxonrasib is already being tested in a Phase 3 trial. This indicates some confidence in its safety, as treatments usually need to prove they are relatively safe in earlier phases before reaching this stage.

Overall, early findings suggest that daraxonrasib could be well-tolerated by patients, with manageable side effects. However, deciding to join a trial is a personal choice, and discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Daraxonrasib is unique because it offers a new approach to treating non-small cell lung cancer by specifically targeting genetic mutations within cancer cells. Unlike traditional treatments like chemotherapy, which attack both healthy and cancerous cells, Daraxonrasib is designed to hone in on specific molecular targets, potentially reducing side effects and improving effectiveness. Researchers are excited about this treatment because it represents a more personalized approach to cancer therapy, which could lead to better outcomes for patients with certain genetic profiles.

What evidence suggests that daraxonrasib might be an effective treatment for non-small cell lung cancer?

Research has shown that daraxonrasib, which participants in this trial may receive, may help treat non-small cell lung cancer (NSCLC) with RAS mutations. In earlier studies, this treatment shrank tumors in over a third of patients. The positive effects lasted an average of 15.1 months, indicating long-lasting benefits. Additionally, early tests showed a decrease in cancer-related DNA in the blood, suggesting the drug effectively targets cancer cells. These findings suggest daraxonrasib could be a promising option for patients with this type of lung cancer. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced non-small cell lung cancer (NSCLC) that can't be cured by surgery or radiation. They should have tried up to two treatments before, including immunotherapy and chemo, and must have a specific RAS gene mutation. Participants need to be able to swallow pills, have decent physical health (ECOG status of 0 or 1), and their organs must work well.

Inclusion Criteria

My cancer can be measured using standard imaging tests.

I am fully active or restricted in physically strenuous activity but can do light work.

My lung cancer cannot be cured with surgery or radiation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either daraxonrasib or docetaxel chemotherapy

Up to approximately 4 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 4 years

What Are the Treatments Tested in This Trial?

Interventions

• Daraxonrasib

Trial Overview

The study tests Daraxonrasib, a new drug targeting the RAS(ON) protein in cancer cells, against docetaxel, an established chemotherapy medication. The goal is to see if Daraxonrasib is safe and works better for patients who've already had some treatment for NSCLC.

How Is the Trial Designed?

Group I: daraxonrasib Experimental Treatment 1 Intervention

study drug

Group II: docetaxel Active Control 1 Intervention

Patients randomized to the comparator control arm will receive docetaxel as the standard of care therapy.

Who Is Running the Clinical Trial?

Revolution Medicines, Inc.

Lead Sponsor

Trials

14

Recruited

4,500+

Published Research Related to This Trial

CT-guided core-needle biopsy is a safe and effective method for obtaining tissue samples from patients with advanced non-small-cell lung cancer (NSCLC) for EGFR gene mutation analysis, with no life-threatening complications reported in the study of 17 patients.

In this study, 70.6% of patients had EGFR gene mutations, and those with mutations showed a significantly higher response rate (91.7%) to the EGFR inhibitor gefitinib compared to nonmutants, who had a 0% response rate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Computed tomography-guided core-needle biopsy specimens demonstrate epidermal growth factor receptor mutations in patients with non-small-cell lung cancer. Chen, CM., Chang, JW., Cheung, YC., et al.[2018]

Efficacy outcomes from early phase trials of targeted therapies for oncogene-driven lung cancer, such as objective response rate (ORR) and progression-free survival (PFS), have historically been consistent with those from later phase trials, suggesting reliability in early trial results.

This consistency implies that early phase trials can provide valuable insights for regulatory approvals and the design of future clinical trials, potentially streamlining the development of new lung cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of targeted therapies for oncogene-driven lung cancer in early single-arm versus late phase randomized clinical trials: A comparative analysis. Tan, AC., Tan, SH., Zhou, S., et al.[2022]

Gefitinib, an EGFR inhibitor, was effective in shrinking tumors in two patients with advanced non-small cell lung carcinoma (NSCLC) before they underwent surgery, demonstrating its potential as a preoperative treatment.

Both patients experienced significant tumor reduction and underwent potentially curative surgeries, but they relapsed after stopping adjuvant gefitinib therapy, indicating the need for further research on long-term outcomes and survival benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Down-staging of EGFR mutation-positive advanced lung carcinoma with gefitinib followed by surgical intervention: follow-up of two cases. Levchenko, EV., Moiseyenko, VM., Matsko, DE., et al.[2018]

Sotorasib is the first commercially available KRASG12C inhibitor, showing promise in improving outcomes for patients with KRASG12C-mutated non-small cell lung cancer (NSCLC), which is prevalent among smokers.

Despite its potential, there are ongoing questions about sotorasib's effectiveness in the brain, optimal dosing, and how it compares to standard treatments, highlighting the need for further research on resistance mechanisms and combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of sotorasib for the treatment of patients with non-small cell lung cancer with KRASG12C mutations. Strohbehn, GW., Sankar, K., Qin, A., et al.[2022]

Citations

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onclive.com

onclive.com/view/daraxonrasib-generates-clinical-activity-with-manageable-safety-in-ras-mutant-nsclc

Daraxonrasib: Clinical Activity in RAS-Mutant NSCLC

Daraxonrasib showed a 38% overall response rate in RAS-mutant NSCLC patients, with a median response duration of 15.1 months. Treatment-related ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06881784

Study of Daraxonrasib (RMC-6236) in Patients With RAS ...

This is a global, randomized, open-label, Phase 3 study designed to evaluate whether treatment with daraxonrasib will improve progression free survival ...

3.

ir.revmed.com

ir.revmed.com/news-releases/news-release-details/revolution-medicines-shares-new-clinical-results-supporting

Revolution Medicines Shares New Clinical Results ...

The median overall survival (OS) was 13.1 (95% CI, 10.9 – NE) and 15.6 months (95% CI, 10.9 – NE). Median follow-up was 16.7 months. RASolute ...

4.

aacrjournals.org

aacrjournals.org/cancerres/article/85/8_Supplement_2/LB218/761318/Abstract-LB218-Early-reduction-in-circulating

Abstract LB218: Early reduction in circulating tumor DNA ...

Early reduction in circulating tumor DNA (ctDNA) is associated with clinical activity of daraxonrasib (RMC-6236) in RAS mutant non-small cell ...

5.

jto.org

jto.org/article/S1556-0864(25)00201-1/pdf

Safety and clinical activity of daraxonrasib (RMC-6236) in ...

Clinical activity is reported in patients treated at 120–. 220 mg with RAS G12X mutant NSCLC receiving 1 or 2 prior lines of therapy, including ...

6.

jto.org

jto.org/article/S1556-0864(25)00201-1/fulltext

6MO: Safety and clinical activity of daraxonrasib (RMC ...

We present results for daraxonrasib in RAS mutant (RASmut) NSCLC from the ongoing phase I Study (NCT05379985), as of a Sep 30 2024 data cutoff. Methods.

7.

jto.org

jto.org/article/S1556-0864(25)00201-1/abstract

Safety and clinical activity of daraxonrasib (RMC-6236) in ...

Patients with previously treated NSCLC have a high unmet medical need, with a median reported overall survival (OS) of <1 year. RAS mutations are the most ...

8.

ir.revmed.com

ir.revmed.com/news-releases/news-release-details/revolution-medicines-present-updated-elironrasib-safety-and

Revolution Medicines to Present Updated Elironrasib ...

Revolution Medicines to Present Updated Elironrasib Safety and Efficacy Data in Patients with KRAS G12C Non-Small Cell Lung Cancer Following ...