A Phase III Study of RMC-6236 in Patients with Previously Treated NSCLC with RAS Mutations

Summary description of the study

This study is being conducted at many study centers around the world. This study is a randomized, open-label clinical trial. 'Open-label' means that both the patients and the investigators know which patients are receiving RMC-6236 or Docetaxel. 'Randomized' means that patients are assigned either RMC-6236 or Docetaxel randomly. There is a screening period in this study during which the investigators determine whether the patient's tumor has a RAS mutation. This is followed by a pre-screening period (during which patients meet with the investigators and undergo tests to determine if they can participate in the study). Each patient may be asked to visit the study center up to three times during these periods. This is followed by a treatment period and a follow-up period. During the treatment period, half of the patients will receive RMC-6236 and the other half will receive Docetaxel. Patients will receive the study medication as long as they tolerate it, until their cancer worsens, they decide to discontinue treatment, or the study is terminated. Within 30 days after the patient has received the last dose of the study medication, a visit for treatment completion/safety follow-up will take place. After that, they will be contacted every 3 months until the end of the study.

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Intervention under investigation

The study medication is administered in 21-day cycles. RMC-6236 is a tablet taken by mouth with a glass of water. Patients will receive RMC-6236 once daily during each cycle. Docetaxel is administered on the first day of each cycle as a liquid infusion into a vein. Primary (main objective): To investigate the effect of RMC-6236 compared to that of Docetaxel on survival in patients with NSCLC and specific RAS mutations. Primary measurements: The investigators will record the duration of time during and after receiving the study medication that a patient lives without disease progression, as well as the duration of time during and after receiving the study medication that a patient remains alive. Secondary objectives: To investigate the effect of RMC-6236 compared to that of Docetaxel on survival in patients with NSCLC with a RAS mutation (all mutations) and to investigate the effect of RMC-6236 compared to that of Docetaxel on tumor shrinkage in patients with NSCLC with a RAS mutation (all mutations). Secondary measurements: The investigators will record the duration of time during and after receiving the study medication that a patient lives without disease progression, as well as the duration of time during and after receiving the study medication that a patient remains alive. The investigators will record the number of patients whose tumors disappear, remain the same, or grow or shrink during treatment.

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Disease under investigation

Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. The patients in this study have NSCLC that has spread from its original site to surrounding tissue or other parts of the body. Some patients with NSCLC have cancer cells that show changes (mutations) in the RAS genes, which produce RAS proteins. The RAS gene acts like a switch that helps control the growth and division of cells. When there is a mutation in the RAS gene, the switch gets stuck in the 'On' position. This causes the cells to grow and divide too much. These changes stimulate the cancer cells to grow and multiply. There are three different RAS genes that can have mutations at different locations in the gene. The patients included in the study also have a change in the RAS genes. Although lung cancer can go into remission after the first-line treatment, it can also grow back. Options for second-line treatment are limited when first-line treatment options fail. Second-line treatment is usually done with chemotherapy. 'Chemotherapy' is a drug that aims to stop cancer growth but also damages normal cells. One of the commonly used chemotherapeutics is called Docetaxel. RMC-6236 is a potential new drug that blocks RAS proteins and mutations and may limit the growth and spread of cancer cells. RMC-6236 has shown anti-cancer effects in other studies. This study compares the effects of RMC-6236 with that of Docetaxel in NSCLC.

(BASEC)

Sponsor

Sponsor: Revolution Medicines, Inc. Sponsor’s representative in Switzerland: IQVIA AG, Branch Basel

(BASEC)

Name of the authorising ethics committee (for multicentre studies, only the lead committee)

Ethics Committee Vaud

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Date of authorisation

16.09.2025

(BASEC)

Results of the trial