KRAS G12C-mutant pancreatic ductal adenocarcinoma: the decisions you may face
3 treatment settings, 3 with more than one named option. Each section lays out the options the standard of care names, what each is for, the trials behind them with their recorded results, the side effects and cautions on record, and questions to ask. Built from the cancer page's standard-of-care rows; nothing here is advice for your case.
First line
Chemotherapy as for other pancreatic adenocarcinoma: modified FOLFIRINOX, NALIRIFOX or gemcitabine plus nab-paclitaxel; G12C inhibitors are not approved first line.
FOLFIRINOX is a four-drug chemotherapy combination that, in 2011, became the first treatment to meaningfully extend life in metastatic pancreatic cancer; it is now the standard before and after surgery.
NALIRIFOX is a version of FOLFIRINOX using a liposome-wrapped irinotecan, approved in 2024 as a first-line option for metastatic pancreatic cancer.
Gemcitabine plus nab-paclitaxel is the gentler of the two standard chemotherapy backbones for pancreatic cancer, and the base on which most new drugs are being tested.
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
No side-effect rates or interaction flags are recorded for these options yet. The side-effect lookup and interaction checker cover the products that have them.
- Between FOLFIRINOX / mFOLFIRINOX, NALIRIFOX (liposomal irinotecan + oxaliplatin + 5-FU/LV) and Gemcitabine + nab-paclitaxel, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Pancreatic Adenocarcinoma), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (first line), which of the standard options do you recommend and why?Why: Guideline options include: Chemotherapy as for other pancreatic adenocarcinoma: modified FOLFIRINOX, NALIRIFOX or gemcitabine plus nab-paclitaxel; G12C inhibitors are not approved first line.
- Am I a candidate for FOLFIRINOX / mFOLFIRINOX, NALIRIFOX (liposomal irinotecan + oxaliplatin + 5-FU/LV), Gemcitabine + nab-paclitaxel, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Add these to your appointment list, or take the full question set for this cancer.
After first-line chemotherapy
Daraxonrasib (RASolute 302, approved for pancreatic cancer irrespective of KRAS subtype); sotorasib or adagrasib as NCCN-listed options on the CodeBreaK 100 and KRYSTAL-1 cohorts.
The first drug that blocks all active RAS variants, approved by the FDA in August 2026 for metastatic pancreatic cancer, where KRAS drives 90% of tumours.
Sotorasib (Lumakras) was the first drug to hit KRAS, approved in 2021 after four decades of failure.
Adagrasib was the second KRAS G12C inhibitor, with a long half-life and brain penetration, and is approved in lung and colorectal cancer.
Drugs against the most common cancer gene, considered impossible to target until sotorasib in 2021.
- First drugs for a 40-year-old target
- Metastatic PDAC after one prior line of chemotherapy: daraxonrasib vs investigator's choice chemotherapy
OS 13.2 vs 6.7 months, HR 0.40.
Overall survival (months): Daraxonrasib 13.2 vs Chemotherapy (gemcitabine/nab-paclitaxel or mFOLFOX6) 6.7 · HR 0.4 · source
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Hepatotoxicity · CodeBreaK 100 | 25% | 12% |
| Interstitial lung disease · CodeBreaK 100 | 2.2% | 1.1% |
| Diarrhoea · CodeBreaK 100 | 42% | - |
| Musculoskeletal pain · CodeBreaK 100 | 35% | - |
- No adjustment for mild impairment; hepatotoxicity is common and worse after recent immunotherapy.
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Hepatotoxicity · KRYSTAL-1 NSCLC | 37% | 10% |
| Dyspnoea · KRYSTAL-1 NSCLC | 35% | 10% |
| Fatigue · KRYSTAL-1 NSCLC | 59% | 7% |
| Musculoskeletal pain · KRYSTAL-1 NSCLC | 41% | 7% |
- Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
- Modest durability as monotherapy
- Adaptive RTK feedback requires combinations
- Between Daraxonrasib, Sotorasib, Adagrasib and the other options, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in RASolute 302, and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- Which side effects of Sotorasib or Adagrasib are most likely for me, which are reversible, and which would make us stop?Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Pancreatic Adenocarcinoma), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (after first-line chemotherapy), which of the standard options do you recommend and why?Why: Guideline options include: Daraxonrasib (RASolute 302, approved for pancreatic cancer irrespective of KRAS subtype); sotorasib or adagrasib as NCCN-listed options on the CodeBreaK 100 and KRYSTAL-1 cohorts.
- Am I a candidate for Daraxonrasib, Sotorasib, Adagrasib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of RASolute 302 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Add these to your appointment list, or take the full question set for this cancer.
Clinical trials
Elironrasib with daraxonrasib, olomorasib, glecirasib and other G12C-selective inhibitors alone or with chemotherapy or EGFR antibodies.
A next-generation KRAS G12C drug that hits the active form of the protein, from the same company as daraxonrasib.
Olomorasib is Lilly's KRAS G12C pill, designed to combine safely with immunotherapy in first-line lung cancer.
Glecirasib is Jacobio's KRAS G12C inhibitor, approved in China in 2024 for previously treated non-small cell lung cancer with that mutation, and in a phase 3 trial against docetaxel.
- Study of Elironrasib and Daraxonrasib as Monotherapies and Combination Therapy in Participants With Advanced KRAS G12C Mutant Solid TumorsPhase 1/2NCT06128551534 peopleevidence 27Tests ElironrasibPhase 1b/2, Multicenter, Open-label, Dose Escalation and Dose Expansion Study of Elironrasib and Daraxonrasib as Monotherapies and Combination Therapy in Patients With Advanced KRAS G12C-Mutated Solid Tumors
No headline result recorded yet.
- Study of LY3537982 in Cancer Patients With a Specific Genetic Mutation (KRAS G12C)Phase 1/2NCT04956640540 peopleevidence 27Tests OlomorasibA Phase 1/2 Study of LY3537982 in Patients With KRAS G12C-Mutant Advanced Solid Tumors
No headline result recorded yet.
- A Phase II Study Evaluating JAB-21822 Monotherapy in Adult Patients With Pancreatic Cancer and Other Solid Tumors Harboring the KRAS p.G12C Mutation.Phase 2NCT0600828888 peopleevidence 30Tests GlecirasibA Single-arm, Multicenter, Open-label Phase II Clinical Study Evaluating the Efficacy and Safety of JAB-21822 Monotherapy in Patients With Locally Advanced or Metastatic Pancreatic Cancer and Other Solid Tumors Harboring the KRAS p.G12C Mutation.
No headline result recorded yet.
No side-effect rates or interaction flags are recorded for these options yet. The side-effect lookup and interaction checker cover the products that have them.
- Between Elironrasib, Olomorasib and Glecirasib, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in Study of Elironrasib and Daraxonrasib as Monotherapies and Combination Therapy in Participants With Advanced KRAS G12C Mutant Solid Tumors and Study of LY3537982 in Cancer Patients With a Specific Genetic Mutation (KRAS G12C), and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Pancreatic Adenocarcinoma), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (clinical trials), which of the standard options do you recommend and why?Why: Guideline options include: Elironrasib with daraxonrasib, olomorasib, glecirasib and other G12C-selective inhibitors alone or with chemotherapy or EGFR antibodies.
- Am I a candidate for Elironrasib, Olomorasib, Glecirasib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of Study of Elironrasib and Daraxonrasib as Monotherapies and Combination Therapy in Participants With Advanced KRAS G12C Mutant Solid Tumors and Study of LY3537982 in Cancer Patients With a Specific Genetic Mutation (KRAS G12C) apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Add these to your appointment list, or take the full question set for this cancer.