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First‑Line Study of Zoldonrasib (RMC‑9805) Drug Combination vs Gemcitabine/Nab‑Paclitaxel in Patients with Metastatic KRAS G12D‑Mutated Pancreatic Cancer

Verified siteRegistered drugNo placebo
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What is this trial about?

A plain-language summary of the goals, design and what participants do

The study involves patients with Pancreatic Adenocarcinoma that has spread to other parts of the body, known as metastatic disease. In this type of cancer, a specific genetic change called KRAS G12D is often present, which means a small part of the tumor’s DNA is altered. The aim of the research is to find out whether a new combination of medicines can work better than the current standard chemotherapy when used as the first treatment given after diagnosis.

One group will receive two experimental oral tablets taken by mouth: one containing Zoldonrasib and the other containing Daraxonrasib. The other group will receive the usual chemotherapy delivered through an intravenous infusion (a drip into a vein), which includes the drugs gemcitabine and nab-paclitaxel. The oral medicines are taken at home, while the intravenous drugs are given in a clinic or hospital setting.

Participants are assigned to one of the two treatment options by chance and will follow a schedule of regular visits for safety checks, blood tests, and imaging scans to see how the cancer is responding. They will also complete questionnaires about pain and overall well‑being. Treatment continues until the cancer grows, side effects become too severe, or the participant chooses to stop. The study is open‑label, meaning both the doctors and participants know which treatment is being given.

The research process

The trial runs in 10 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Enrollment and Randomization

    After giving informed consent, you are assigned by the study to one of two treatment groups. The assignment is random, meaning it is decided by chance and not by any personal factor.

    The two possible groups are: the test group that receives the oral medicines Zoldonrasib and Daraxonrasib, or the comparator group that receives the intravenous medicines Gemcitabine and Nab‑Paclitaxel.

  2. Step 2

    Baseline Assessments

    Before the first dose, you undergo a series of examinations that include blood tests, vital‑sign measurements, and imaging scans to document the extent of the pancreatic cancer.

    You also complete questionnaires that measure pain and overall quality of life. These results serve as the reference point for later comparisons.

  3. Step 3

    Start of Treatment

    If you are in the test group, you begin taking Zoldonrasib as an oral tablet at a dose of 1200 mg and Daraxonrasib as an oral tablet at a dose of 300 mg. The tablets are swallowed with water as directed by the study protocol.

    If you are in the comparator group, you receive Gemcitabine by intravenous (IV) infusion at a dose of 1000 mg per square meter of body‑surface area (mg/m²) and Nab‑Paclitaxel by IV infusion at a dose of 125 mg/m². The infusion is administered in a clinical setting by qualified staff.

  4. Step 4

    Repeated Treatment Cycles

    Treatment is given in repeated cycles as defined by the study protocol. Each cycle continues until the end of the study, disease progression, or an unacceptable level of side effects.

    Oral tablets are taken on the schedule specified in the protocol (for example, daily), while IV infusions are given on the days scheduled by the study team.

  5. Step 5

    Regular Monitoring Visits

    You attend clinic visits at regular intervals. During these visits, health professionals check vital signs, perform blood tests, and ask about any new or worsening symptoms.

    Blood samples are also taken to measure the concentrations of Zoldonrasib and Daraxonrasib (if you are in the test group) to ensure the drugs are at appropriate levels.

  6. Step 6

    Imaging Assessments

    Imaging scans (such as CT or MRI) are repeated during the study to evaluate whether the tumor is shrinking, staying the same, or growing. The scans are interpreted according to standard criteria (RECIST v1.1).

  7. Step 7

    Questionnaire Completion

    At designated visits you complete the EORTC QLQ‑PAN26 pain scale and the EORTC QLQ‑C30 global health status questionnaire. These tools help assess changes in pain and overall quality of life over time.

  8. Step 8

    Management of Side Effects

    If you experience treatment‑related side effects, the study team may adjust the dose, pause treatment, or provide supportive medication, following the protocol’s safety guidelines.

    All side effects, whether mild or serious, are recorded and reported as part of the trial’s safety monitoring.

  9. Step 9

    End of Treatment

    Treatment ends when disease progression is documented, when side effects become unacceptable, or when the planned treatment period is completed.

    You will be informed of the reason for stopping treatment and will receive instructions for the next phase of care.

  10. Step 10

    Post‑Treatment Follow‑Up

    After treatment stops, you continue to have periodic follow‑up visits. These visits focus on monitoring overall health, checking for late side effects, and collecting survival information.

Who can join the trial?

9 criteria

  • Be at least 18 years old (or meet the local age required to agree to join a study) when you sign the consent form.
  • Have an ECOG performance status of 0 or 1, which means you are either fully active (0) or able to do light work but not vigorous activity (1).
  • Have a confirmed diagnosis of pancreatic adenocarcinoma (a type of pancreatic cancer) that has been verified by looking at your tissue under a microscope.
  • Have been told that the cancer has spread to other parts of the body (metastatic disease) no more than 6 weeks before signing the consent form.
  • Not have received any systemic (whole‑body) anticancer treatment for advanced or metastatic pancreatic cancer. If you had treatment before surgery (called neoadjuvant or adjuvant therapy), it is allowed as long as it was finished at least 6 months before the cancer spread.
  • Have measurable metastatic disease according to RECIST v1.1, a set of rules doctors use to measure tumor size on scans.
  • Have a documented KRAS G12D mutation identified by a validated assay (a reliable test that shows a specific genetic change in your tumor).
  • Have tumor tissue available that meets the study’s requirements.
  • Have adequate organ function, meaning your blood, liver, kidney and clotting tests are within normal limits.

Who cannot join the trial?

6 criteria

  • Having a known genetic change (called a driver mutation) that already has an approved targeted medicine, such as changes in the BRCA1 or BRCA2 genes, a condition called microsatellite‑instability high or mismatch repair deficient, or an NTRK gene fusion.
  • Having previously received a medicine that blocks the MAPK pathway, which is a specific cell‑signaling route used by some cancers.
  • Having active or untreated cancer that has spread to the brain or spinal fluid covering membranes (known as central nervous system metastatic disease or leptomeningeal disease).
  • Having any health problem that could make it difficult to swallow, digest, or absorb the study medicines.
  • Having had a major operation (such as major surgery) within the 28 days before being assigned to a treatment group.
  • Being unable or unwilling to attend the required study visits or to follow the study procedures.
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Investigated drugs

  • Gemcitabine

    is a chemotherapy drug that is given through an IV. It works by stopping cancer cells from growing and dividing. In this trial it is used as one part of the standard treatment that is compared with the new medicines.

  • Nab‑paclitaxel

    (also called paclitaxel albumin‑bound) is another chemotherapy drug given by IV. It helps to disrupt the structure of cancer cells, making it harder for them to multiply. In the study it is combined with gemcitabine as the standard treatment arm.

  • Zoldonrasib (RMC‑9805)

    is an experimental oral medication that targets a specific mutation (KRAS G12D) found in some pancreatic cancers. By blocking the abnormal signal that drives tumor growth, it aims to slow or stop the cancer. In the trial it is taken together with daraxonrasib to test a new treatment approach.

  • Daraxonrasib (RMC‑6236)

    is an experimental oral drug designed to work on the same KRAS G12D mutation. It is meant to complement zoldonrasib by further inhibiting the cancer‑driving pathway. Patients in the study receive this medication along with zoldonrasib as the new therapy being tested.

What is already known about the treatment

  • Gemcitabine

    This medication is given by intravenous infusion, usually once every week. It is an approved chemotherapy drug that is widely used for pancreatic cancer and several other solid tumors. Gemcitabine works by blocking the building blocks needed for DNA, which stops cancer cells from multiplying. It belongs to the class of nucleoside analog chemotherapeutic agents.

  • Zoldonrasib (RMC-9805)

    Zoldonrasib is taken as an oral tablet taken daily. It is an investigational drug that is currently being studied in clinical trials for KRAS G12D‑mutated pancreatic cancer. The medicine blocks the KRAS protein, a key signal that tells cancer cells to grow, thereby slowing tumor growth. It is classified as a targeted KRAS inhibitor.

  • Daraxonrasib (RMC-6236)

    Daraxonrasib is also an oral tablet taken once a day and has received orphan‑drug status for a rare form of pancreatic cancer. It is an experimental therapy still in clinical testing, aimed at tumors with KRAS G12D mutations. The drug binds to the KRAS protein and prevents it from sending growth signals to the cell. It is categorized as a targeted KRAS inhibitor.

  • Paclitaxel Albumin‑Bound (Nab‑Paclitaxel)

    This medication is administered by intravenous infusion, usually once every three weeks. It is an approved chemotherapy used together with gemcitabine for advanced pancreatic cancer. Nab‑paclitaxel works by stabilizing the microtubules inside cells, which stops cancer cells from dividing properly. It belongs to the taxane class of chemotherapy agents.

Investigated diseases

Pancreatic Adenocarcinoma - Pancreatic adenocarcinoma is a cancer that starts in the glandular cells of the pancreas. It typically begins as a small tumor in the head or body of the pancreas and can grow to invade nearby blood vessels and ducts. As it expands, cancer cells may spread to surrounding organs such as the duodenum, liver, and lymph nodes. Over time, the disease can disseminate through the bloodstream to distant sites like the lungs. The growth of the tumor often leads to blockage of the pancreatic duct, causing digestive problems. The disease progresses silently until it becomes large enough to cause symptoms.
Trial detailsLast updated 14 Oct 2026
Age18+ yearsPhasePhase IIITrial ID2025-524969-24-00Protocol codeRMC-9805-309Estimated enrolment223 patientsSponsorRevolution Medicines Inc.

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