Pancreatitis or inflammation of the pancreas comes in both acute and chronic forms and has long been appreciated as a risk factor for developing pancreatic cancer. While common and in most cases mild, severe acute pancreatitis can be fatal due to severe inflammation causing local damage that can have serious systemic consequences. The ability to predict which patients who initially present with acute pancreatitis will develop severe disease is currently limited. With the adoption of AI, new models may help to more accurately predict patients who will develop severe and life-threatening disease, and in the future may be able to help predict those that may develop pancreatic cancer.

Peter Hegyi, MD, PhD and Tamas Gonda, MD, were awarded a collaborative Hirshberg Foundation Seed Grant in 2023 to evaluate the use of AI and machine learning to predict which patients will develop severe acute pancreatitis and to predict those who may develop pancreatic cancer. Dr. Hegyi, Professor and Director of the Institute for Pancreatic Diseases at Semmelweis University in Budapest, Hungary, and Dr.Tamas Gonda, Associate Professor of Medicine in Gastroenterology at New York University Grossman School of Medicine, sought build a database of well characterized acute pancreatitis patients across NYU and Semmelweis University to develop a model to predict acute pancreatitis severity. They also set out to build a multi-institutional coalition to identify cases and imaging where pancreatic cancer was diagnosed with 2 years of acute pancreatitis to then extend this deep learning model to predict which acute pancreatitis patients may later develop pancreatic cancer. 

The team developed and validated a deep learning model that predicts acute pancreatitis severity using contrast-enhanced CT scans. Their model was trained on over 10,000 CT studies and then fine-tuned on over 500 additional cases where severity outcome was known. In both internal and external data sets, the new deep-learning model outperformed established prediction tools. The model was then used to analyze a cohort of images from patients with known outcomes (also called a retrospective analysis) and it was able to identify 73% of patients that went on to develop severe acute pancreatitis. These results support the continued validation of early, automated risk triage for acute pancreatitis. A recent paper, Deep learning-based prediction of acute pancreatitis severity from abnormal CT with multicenter external validation, was published in the May 2026 journal Radiology Advances.

Current and future research will focus the new machine learning algorithms on images from patients with acute pancreatitis who later develop pancreatic cancer. This will train the programs to identify image-based changes in the hopes of generating a predictive model to stratify these patients’ cancer risk at the time of acute pancreatitis onset. The ability to use image-based biomarkers for this high-risk population will lead to earlier pancreatic cancer diagnoses and better treatment options. 

Early detection remains one of the greatest opportunities to change outcomes for pancreatic cancer patients. The Hirshberg Foundation is committed to funding bold and innovative research that makes early detection possible. Better diagnostic approaches offer the greatest opportunity for successful treatment and improved survival, yet too many patients are still diagnosed at advanced stages. AI-driven imaging represents one of many promising approaches with the potential to change how pancreatic cancer is found and treated. Continued funding is critical to move these discoveries from the laboratory into real-world clinical care. The power to detect pancreatic cancer sooner helps expand treatment options and save lives.

The wait is over. On Sunday May 31st 2026, Brian M Wolpin MD, MPH, the Director of the Hale Family Center for Pancreatic Cancer Research at Dana Farber Cancer Institute, presented the highly anticipated results for Revolution Medicine’s phase 3 clinical trial, RASolute 302, evaluating daraxonrasib in metastatic pancreatic cancer at the 2026 American Society for Clinical Oncology Annual Meeting in Chicago.

Mutations in KRAS (one of three forms of RAS) are present in >90% of pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer, resulting in uncontrolled tumor cell growth and survival. Daraxonrasib, a RAS(ON) inhibitor, binds the active form of the RAS protein to block growth and survival signaling to cancer cells. Remarkably, daraxonrasib treatment was associated with a 60% reduction in the risk of death for the patients enrolled in this study. These findings resulted in a standing ovation and a round of applause from clinicians in the audience who know what a game changer these results are for patients with pancreatic cancer.

Most treatments come with side effects and that is particularly true for cancer treatments. For patients in this trial, almost 100% reported at least one adverse event. However, the types of adverse events differed between the patients on daraxonrasib and those on chemotherapy. Rashes and mouth inflammation were the most common high grade adverse events for the daraxonrasib group while low white blood cells (neutropenia), low platelets, and anemia were the most common high grade adverse events for the chemotherapy group. Most importantly, while adverse events caused a reduction in the amount of drug given to patients in both groups, the discontinuation rate was only 1.2% for daraxonrasib group compared to 11.2% in the chemotherapy, suggesting the of side effects for daraxonrasib were more manageable than chemotherapy causing less patients to stop treatment early.

Simultaneous to Sunday’s ASCO presentation, the New England Journal of Medicine published an article “Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer” detailing the trial results. These results are especially meaningful for UCLA as it was one of the RASolute 302 participating locations with Dr. Zev Wainberg, the Co-Director of the UCLA GI Oncology Program and member of the Agi Hirshberg UCLA Center for Pancreatic Diseases, as a lead author of the study. Remarking on the powerful results, Dr. Wainberg said “Now, for the first time, we have demonstrated that targeted inhibition of RAS using an oral inhibitor is changing the landscape of this terrible disease. Seeing this magnitude of benefit in a randomized phase 3 study is very encouraging for all patients with advanced pancreatic cancer and is a paradigm shift in this deadly disease”.

After the presentation Dr. Jennifer J. Knox, MD, MSc a clinical investigator at the Princess Margaret Cancer Center in Toronto, Canada noted “My key takeaway point is that we have a new standard of care in the second line setting with daraxonrasib” highlighting how these results will transform that care for many patients with metastatic pancreatic cancer. The FDA already has daraxonrasib on track for an accelerated approval and on May 1st, 2026, granted Revolution Medicines permission for an expanded access program (see our What Patients Need To Know article) allowing patients trials to access daraxonrasib outside of the clinical trial setting.

Revolution Medicines has two additional ongoing phase 3 trials evaluating daraxonrasib in metastatic patients without any prior chemotherapy (called the first line setting) as well as in patients with localized disease who have undergone surgical resection underscoring the promise of RAS inhibition to all patients with pancreatic cancer. Similarly, as other solid tumors such as non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) harbor RAS mutations, there are clinical trials underway to assess daraxonrasib for indications outside of PDAC.

For patients, this is a huge step towards bringing new treatments and new hope to a pancreatic cancer diagnosis. It’s important to remember that this breakthrough occurred due to years of hard work and dedication from an entire field with the goal to bring better options and outcomes to pancreatic cancer patients that desperately need them. With clinical validation for RAS inhibition now accomplished, we must now continue the hard work and capitalize on momentum to increase the length and quality of life for all pancreatic cancer patients.

RASolute 302 Clinical Trial Details

Who: Patients with metastatic PDAC who had undergone at least one round of chemotherapy with either gemcitabine or fluorouracil were eligible for enrollment.

What: 500 enrolled patients were treated with either 300 mg of daraxonrasib once daily, or with one of the following chemotherapy protocols: gemcitabine plus nab-paclitaxel, modified FOLFIRINOX, FOLFOX, or liposomal irinotecan plus fluorouracil.

Where: The trial was run at more than 60 locations across the United States, France, Germany, Italy, Japan, Puerto Rico, and Spain.

Results

While a majority of PDAC patients have KRAS G12 mutations, daraxonrasib does not target a specific form of RAS (KRAS, NRAS, or HRAS), nor does it target specific mutations. The trial was therefore open to all patients regardless of RAS gene status.

Across all patients, the following results were observed:

Tolerability

Most common adverse events (any grade) — daraxonrasib group:

• Rashes — 85.5%
• Diarrhea — 58.1%
• Stomatitis (mouth inflammation) — 53%
• Nausea — 46.5%
• Vomiting — 36.9%

High-grade (Grade ≥3) adverse events: rashes (13.7%) and stomatitis (12%)

Most common adverse events (any grade) — chemotherapy group:

• Fatigue — 44.4%
• Anemia — 39.7%
• Nausea — 39.3%
• Neutropenia (reduction in white blood cells) — 38.3%
• Diarrhea — 37.9%
• Thrombocytopenia (reduction in platelets) — 33.2%
• Peripheral neuropathy — 25.2%

High-grade (Grade ≥3) adverse events: neutropenia (27.6%) and anemia (16.4%)

While the 5-year survival rate for pancreatic cancer has increased over the last decade to 13%, it continues to be one of the toughest cancers to diagnose and treat. One contributing factor is a lack of biomarkers for disease detection and treatment response. Biomarkers are measurable signs that coincide with biological processes, such as a protein that is only found in people with pancreatic cancer and decreases proportionally with tumor size. When identified, biomarkers can be used for diagnosis, characterization of types of cancer, decisions about which treatment may be beneficial, and can be used to monitor treatment response. 

A biomarker currently used for multiple cancers is carbohydrate antigen 19-9 (also called cancer antigen or CA 19-9) and is the only biomarker currently approved for identifying pancreatic cancer.  Research is focused on identifying new biomarkers for pancreatic cancer to facilitate early diagnosis, characterize different subsets of patients, and monitor disease progression. Howard Katz, Professor of Materials Science and Engineering at Johns Hopkins University and a 2017 Hirshberg Foundation Seed Grant Awardee in collaboration with Kevin Yarema, Associate Professor of Biomedical Engineering at Johns Hopkins University, have turned to an emerging technique called glycoengineering to identify novel biomarkers for pancreatic cancer. This work is detailed in their recent Journal of Biological Chemistry publication titled Profiling the pancreatic cancer secretome with metabolic glycoengineering. 

Metabolic glycoengineering is the process of introducing non-natural sugar molecules to cells. Cells then use these sugars in biochemical pathways to make proteins; these new proteins are tagged with the synthetic sugar molecules and are used to make cellular components or can be secreted. Katz and Yarema’s groups used this technique to identify all the proteins secreted (called the secretome) by pancreatic cancer cells, identifying several proteins as potential biomarkers. Research is continuing to evaluate the use of the identified proteins as biomarkers for pancreatic cancer and specifically for early disease. An important and unanticipated aspect of this study was that their method increased the production of extracellular vesicles by the cells. As extracellular vesicles have therapeutic potential, Katz and Yarema are also extending their research to ask whether this approach could be used as a theranostic (a technique that combines diagnostic and therapeutic capabilities) strategy.

Though Dr. Katz’s research has mainly focused on electronic material chemistry; he has been driven to find ways to use his training to increase early detection of pancreatic cancer by personal experiences of friends and family with the disease. Through collaboration with Dr. Yarema, he has been able to leverage his experience and expertise to demonstrate the possibility of using this unique technique to identify and create new biomarkers for pancreatic cancer. On his 2017 Seed Grant, Dr Katz says “I am extraordinarily grateful to the Hirshberg Foundation for opening this opportunity to me and hopefully contributing to the urgently needed early detection and eventual eradication of pancreatic cancer.”

Research like this is possible because of donor support. Hirshberg Foundation Seed Grants give scientists the early funding needed to test bold ideas, generate critical data, and pursue discoveries that may otherwise go unexplored. Today’s Seed Grant projects lay the groundwork for tomorrow’s advances in pancreatic cancer detection, treatment, and survival.

The FDA has granted permission for Revolution Medicines to provide access to its investigational RAS inhibitor, daraxonrasib, through an Expanded Access Program (EAP) for certain patients with metastatic pancreatic ductal adenocarcinoma (PDAC).

Previously, daraxonrasib was available only through participation in one of the company’s clinical trials. The new expanded access pathway may allow some patients with previously treated metastatic PDAC to receive the drug outside of a trial setting when other treatment options are limited.

Daraxonrasib has generated significant interest following encouraging results from the phase III RASolute 302 clinical trial. In that study, patients with previously treated metastatic pancreatic cancer (PDAC) who received daraxonrasib lived a median of 13.2 months, compared with 6.7 months for patients receiving chemotherapy. Researchers also reported that side effects were generally manageable and consistent with expectations for this type of therapy. Based on these promising findings, Revolution Medicines requested permission to initiate an Expanded Access Protocol (EAP) for their experimental RAS(ON) inhibitor. 

An EAP allows physicians in the US to request use of investigational drugs for patients not enrolled in the drug’s clinical trials. Sometimes called “compassionate use,” this pathway may allow patients with serious illnesses to receive investigational treatments before full FDA approval. Like a clinical trial, expanded access programs have strict criteria and require physician oversight.

For daraxonrasib, the EAP is intended for adult patients with previously treated metastatic pancreatic cancer who:

• Are no longer benefiting from standard treatment options
• Are unable to enroll in an active clinical trial
• Meet specific medical eligibility requirements established by the program

The first step to accessing daraxonrasib through the EAP is to speak with your oncology team. 

Patients cannot apply for daraxonrasib on their own. Requests must be submitted directly by a treating physician to Revolution Medicines. If a physician believes a patient may qualify, the company will review the request and determine eligibility based on medical criteria, regulatory requirements, and drug availability. Access is evaluated on a case-by-case basis.

Because demand for this therapy is high, not every request may be approved. However, the expanded access program represents an important opportunity for some patients who previously had limited options outside of clinical trials.

Patients with metastatic PDAC have few treatment options. Standard first-line therapies typically include chemotherapy, generally FOLFIRONX or the combination of gemcitabine and Nab-paclitaxel and have no other treatment options if these options stop working. 

The emergence of targeted therapies like daraxonrasib reflects meaningful progress in pancreatic cancer research and may offer some patients another treatment pathway that could extend survival and improve quality of life.

Importantly, daraxonrasib is only one part of a broader wave of KRAS-focused research currently underway. Additional clinical trials are already exploring the drug in earlier treatment settings, including as a first-line therapy and in patients who have undergone surgery.

While no single treatment works for everyone, advances like these are helping move pancreatic cancer care toward a more personalized future.

If you are interested in learning more about daraxonrasib or other clinical trial options, consider asking your care team:

• Have I had comprehensive biomarker or genetic testing?
• Could I qualify for a KRAS-targeted therapy or clinical trial?
• Am I eligible for the daraxonrasib Expanded Access Program?
• Are there ongoing clinical trials that may be appropriate for me now or in the future?

Progress in pancreatic cancer research continues to accelerate, and new treatment approaches are offering hope where few options once existed. 

A pancreatic cancer diagnosis can feel overwhelming, especially when navigating treatment decisions, clinical trials, and emerging therapies. Staying informed and connected to experienced care teams can help patients and families navigate these decisions with greater confidence. The Hirshberg Foundation for Pancreatic Cancer Research is here to help patients and families access trusted information, educational resources, and supportive programs throughout every stage of the journey.