A Phase 3, Randomized, Open-Label Study of Zoldonrasib (RMC-9805) Plus Daraxonrasib (RMC-6236) Versus Gemcitabine and Nab-Paclitaxel as First-Line Treatment in Patients with Metastatic KRAS G12D-Mutated Pancreatic Adenocarcinoma (RASolute 309)
This Phase 3 clinical trial is comparing a new combination of targeted medicines against standard chemotherapy for people newly diagnosed with advanced (metastatic) pancreatic cancer. To take part, a person's tumour must have a specific genetic change known as a KRAS G12D mutation. Participants will be placed by chance into one of two groups. One group will receive two new targeted drugs, zoldonrasib and daraxonrasib. The other group will receive standard chemotherapy medicines called gemcitabine and nab-paclitaxel. The main goal of the trial is to find out which treatment keeps the cancer from growing for longer and helps people live longer overall. The trial team will also look closely at side effects and how the treatments affect day-to-day quality of life and pain levels.
At a glance
What is this study about?
Pancreatic cancer is often difficult to treat, particularly when it has spread to other parts of the body (known as metastatic cancer). In many people with this condition, the cancer cells have a fault in a gene called KRAS. This fault acts like a broken switch that stays turned on, telling cancer cells to grow and spread uncontrollably. One of the most common types of this fault is called KRAS G12D.
Historically, it has been very difficult to make medicines that target the KRAS switch directly. Most people are offered standard chemotherapy combinations, such as gemcitabine and nab-paclitaxel, through a drip. While chemotherapy can help shrink or slow down the tumour, doctors are looking for more precise treatments that can attack cancer cells while causing less damage to healthy parts of the body.
This trial is looking at two new experimental drugs called zoldonrasib and daraxonrasib. They are designed to work together to block the faulty KRAS switch directly. By comparing this new drug combination with standard chemotherapy, doctors hope to discover whether these targeted medicines can keep the cancer under control for longer, help patients live longer, and offer a better quality of life.
Key takeaways
- The study tests two new targeted drugs against standard chemotherapy for advanced pancreatic cancer.
- It is specifically for people whose cancer carries the KRAS G12D genetic change.
- This trial is for first-line treatment, meaning you haven't yet received drug therapy for advanced disease.
- Participants are randomly assigned to either the targeted therapy group or the chemotherapy group; there is no placebo.
- Researchers want to find out if the new treatment slows cancer growth and improves life expectancy and quality of life.
Who may be eligible?
This study is for adults aged 18 and over who have been diagnosed with pancreatic adenocarcinoma that has spread (metastatic disease). Because the study tests targeted medicines, a sample of your tumour must be tested to confirm it has the specific KRAS G12D gene change.
The trial is designed as a 'first-line' treatment. This means it is for people who have not yet had chemotherapy or other drug treatments for their advanced pancreatic cancer. If you have only had treatment in the past for an early-stage cancer that was surgically removed, you may still be eligible depending on when that treatment ended.
You will also need to have reasonably good everyday energy levels and healthy organ function (such as your liver, kidneys, and heart) so your body can safely cope with the treatment. Your hospital doctor or the study team will carry out standard blood tests and health checks to confirm whether taking part is safe for you.
Could this study suit you?
Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.
- Are you 18 years of age or older?
- Have you been diagnosed with pancreatic cancer that has spread (metastatic)?
- Has your tumour tested positive for the KRAS G12D gene fault?
- Have you not yet received chemotherapy or drug treatment for advanced pancreatic cancer?
- Are you well enough to attend regular hospital appointments, blood tests, and scans?
What does participation involve?
If you decide to join this study, a computer will assign you by chance (randomly) to one of two treatment groups. One group will take the experimental targeted tablets (zoldonrasib and daraxonrasib), while the other group will receive standard chemotherapy infusions (gemcitabine and nab-paclitaxel) via a drip at the hospital clinic.
You will need to visit the hospital regularly for check-ups, especially in the first few months. Visits will involve blood and urine tests, physical examinations, heart checks (ECGs), and discussions about how you are feeling. Every few weeks, you will have CT or MRI scans to check how your tumour is responding to the medicine. You will also be asked to fill in short questionnaires about your pain levels and daily wellbeing.
You can stay on the trial treatment for as long as it is helping to keep your cancer under control and the side effects are manageable. Even after you stop the trial medicines, the study team will continue to check in on your health periodically.
Potential risks and benefits
Locations (9)
- —UnverifiedAustria
- —UnverifiedNetherlands
- —UnverifiedGermany
- —UnverifiedSweden
- —UnverifiedSpain
- —UnverifiedBelgium
- —UnverifiedNorway
- —UnverifiedFrance
- —UnverifiedItaly
Common questions
What is a KRAS G12D mutation?
It is a specific change or fault in a gene called KRAS. In healthy cells, this gene helps control growth, but when it is mutated, it stays permanently 'switched on', driving the growth of cancer cells.
Can I choose which treatment group I join?
No. A computer assigns you to a group by chance. This is called randomisation, and it helps ensure the comparison between the new treatment and standard chemotherapy is completely fair.
Is there a dummy drug (placebo) in this study?
No. Everyone taking part will receive active cancer treatment—either the two new targeted drugs or standard chemotherapy. No one receives a placebo alone.
How do I know if my tumour has the KRAS G12D change?
Your care team can test a small sample of tumour tissue from a previous biopsy or collect a new sample to check your tumour's genetic makeup.
What happens if my cancer gets worse during the trial?
Your health will be monitored closely with regular scans. If tests show the treatment is no longer working, or if side effects become too troublesome, your doctor will stop the trial treatment and discuss other available care options with you.
How to find out more
Always speak to your GP or specialist before deciding to take part in a study.
Discussion
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