Daraxonrasib for Non-Small Cell Lung Cancer

(RASolve 301 Trial)

Recruiting at 5 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

Trial Summary

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.

What data supports the effectiveness of the drug Daraxonrasib for treating non-small cell lung cancer?

The research highlights that targeted therapies for lung cancer, like sotorasib for KRASG12C mutations, have shown promising results in early trials, which often translate well to larger studies. This suggests that new targeted drugs like Daraxonrasib may also be effective. ^{1 2 3 4 5}

How is the drug Daraxonrasib different from other treatments for non-small cell lung cancer?

Daraxonrasib is unique because it targets the KRASG12C mutation, which was once considered impossible to treat. This makes it similar to sotorasib, a drug that has shown promise in treating non-small cell lung cancer with this specific mutation. ^{1 3 6 7 8}

What is the purpose of this trial?

The purpose of this study is to evaluate the safety and efficacy of a novel RAS(ON) inhibitor compared to docetaxel.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

An evaluation of sotorasib for the treatment of patients with non-small cell lung cancer with KRASG12C mutations. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Randomised, double-blind trial of carboplatin and paclitaxel with daily oral cediranib or placebo in patients with advanced non-small cell lung cancer: NCIC Clinical Trials Group study BR29. [2015]

3. England 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. [2018]

4. Switzerland 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. [2018]

5. Netherlands 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. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

KRAS Inhibitor Continues to Impress in NSCLC. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Brain Mural Cells Express CAR T-cell Target. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Kicking KRAS to tackle lung cancer. [2022]