Comparing the Targeted Therapy Daraxonrasib With or Without Chemotherapy to Chemotherapy Alone for First-Line Treatment of Metastatic Pancreatic Cancer (RASolute 303)

About the Study

This study is testing a new targeted drug called daraxonrasib to see if it helps people with metastatic pancreatic cancer live longer or keep their cancer from growing longer than standard chemotherapy alone. Researchers are comparing daraxonrasib by itself or combined with chemotherapy to standard chemotherapy. 

Daraxonrasib is an oral targeted therapy designed to block a pathway called RAS, which plays a role in many pancreatic cancers. Daraxonrasib is not FDA‑approved and is only available through participation in a clinical trial or through a program known as expanded access. You can read more about expanded access for daraxonrasib. 

What the Study Involves

Participants are randomly assigned (by chance) to one of three groups. Participants do not get to choose which group they will be in. 

Daraxonrasib alone (oral targeted therapy)

Participants in this group will take daraxonrasib orally (by mouth) every day.

Participants will continue taking daraxonrasib as long as it is helping, their cancer isn't growing and side effects are manageable.

Daraxonrasib plus chemotherapy

Participants in this group will take daraxonrasib orally (by mouth) every day.

Participants will also receive two chemotherapy drugs intravenously (injection in the veins).

• Gemcitabine (IV)
• Nab‑paclitaxel (IV)

Participants will receive chemotherapy in 28‑day cycles, with treatment given on specific days during each cycle, followed by rest periods.

Participants in this group will continue taking daraxonrasib and chemotherapy as long as it is helping and side effects are manageable.

Standard chemotherapy alone

Participants in this group will receive two chemotherapy drugs intravenously (injection in the veins).

• Gemcitabine (IV)
• Nab‑paclitaxel (IV)

Participants will receive chemotherapy in 28‑day cycles, with treatment given on specific days during each cycle, followed by rest periods.

Participants in this group will continue taking chemotherapy as long as it is helping and side effects are manageable.

All participants

Participants can expect regular monitoring, which may include:

• Clinic visits including physical exams and vital signs checks.
• Blood tests to check organ function and measure drug levels.
• Imaging scans (such as CT or MRI) to see whether the cancer is shrinking, stable, or growing.
• Questionnaires about symptoms and quality of life, including pain and daily functioning.
• Monitoring for side effects, including recording and grading any adverse events.

Additional Considerations

• Participants are randomly assigned to a treatment group and do not get to choose which treatment they receive. 
• Some participants may receive standard chemotherapy alone.
• Daraxonrasib is investigational and only available through research studies or the expanded access program.

In order to participate, people must meet all of the following:

• Have pancreatic adenocarcinoma (the most common type of pancreatic cancer) that is metastatic (has spread outside the pancreas and surrounding area). 
• Have not received any treatment for metastatic disease.
• Have measurable disease (the cancer can be seen and measured on scans so doctors can track how it responds to treatment).
• Have good overall physical functioning. 
• Have had testing on their cancer to look at a biomarker known as a RAS mutation. People may be eligible regardless of their RAS mutation results (either mutated or not mutated).
• Must be able to swallow oral medication
• Adequate organ function (bone marrow, liver, kidney, coagulation).

People with any of the following cannot join the study:

• Have already received treatment for metastatic pancreatic cancer
• Have previously received a RAS‑targeted therapy.
• Have active or untreated spread to the brain or central nervous system.
• Have any other conditions that may affect the ability to take or absorb the study drug.