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.

From April 17-22, 2026, the American Association for Cancer Research (AACR) held their annual meeting in San Diego, CA. The AACR Annual Meeting brings together clinicians, researchers, and health-care professionals to discuss the latest advancements in cancer treatment and research. Dr. Vinod Balachandran MD, the Director of the Olayan Center for Cancer Vaccines at Memorial Sloan Kettering Cancer Center provided exciting, updated results for a Phase 1 clinical evaluating a therapeutic messenger RNA (mRNA) vaccine for pancreatic cancer. 

Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer and has only a 13 percent 5-year survival rate. While surgery can potentially cure early-stage disease, many patients see recurrence of their tumors even after surgery and chemotherapy. This highlights the urgency for new treatment strategies to enhance the response of patients diagnosed with resectable PDAC. 

One treatment that has been transformative lung cancer and melanoma is immunotherapy. Immunotherapy uses the patient’s own immune system to fight tumor cells; the most widely effective approach has been checkpoint inhibition (anti-PD1/anti-PDL1/anti-CTLA4 therapies). Checkpoint inhibition has so-far been ineffective for pancreatic cancer, but promising early results are being reported for a different immunotherapy approach called a “cancer vaccine.” 

Dr. Balanchadran is the principal investigator for a phase 1 clinical trial evaluating a messenger RNA (mRNA) cancer vaccine called autogene cevumeran in patients diagnosed with resectable PDAC. Started in December 2019, 16 patients were treated with the mRNA vaccine in combination with atezolizumab, a checkpoint inhibitor, and the chemotherapy FOLFIRINOX after surgery to remove their tumor. Dr. Balanchardran’s presentation provided an update on these 16 patients up to 6 years after their treatment. In 50% of patients (8 out of the 16) treatment activated tumor-specific T cells and of those 8 patients, 7 patients (87%) are still alive 4-6 years after treatment. 

While these results are encouraging, the size of this trial was small and needs to be expanded. Based on the strength of these results, a phase 2 clinical trial has been initiated by Genentech in collaboration with BioNTech, to continue to evaluate the potential of autogene cevumeran for PDAC patients. 

What is a cancer vaccine?

A vaccine is a substance used to train or teach a person’s immune system to respond to a specific disease or pathogen. The immune system consists of red and white blood cells. There are multiple types of white blood cells, and each has a specific role to play in an immune response. The role of one type of these white blood cells, the T cells, is to recognize foreign signals (antigens) and trigger an immune response.  

Tumor cells accumulate genetic mutations as they replicate and these mutated genes produce proteins that can be recognized as foreign signals (called neoantigens) by T cells. In many patients with cancer, T cells cannot detect the neoantigens produced by tumor cells and this is commonly seen in pancreatic cancer. A cancer vaccine can introduce neoantigens to a patient’s T cells in a way that can train them to detect and then destroy tumor cells. 

What is autogene cevumeran?

Autogene cevumeran is the name of the personalized cancer vaccine now being developed by BioNTech and Genentech/Roche, also called BNT122 and RO7198457. It is generated from the mutations found in a patient’s own tumor. Patients’ tumors were removed and the DNA from the tumor was sequenced. An algorithm predicted and selected neoantigens specific to each patient to be used as a vaccine. Up to 20 peptides were chosen based on their predicted ability to train T cells, a type of white blood cell, to recognize and destroy tumor cells. 

The American Association for Cancer Research (AACR) held their annual meeting in San Diego, CA from April 17-22, 2026. The AACR Annual Meeting gathers cancer researchers from around the world to share and discuss, not just clinical results, but also the basic and translational research that fuels new therapeutic innovations. Mara Sherman, PhD, an Associate Member of Cancer Biology & Genetics at Memorial Sloan Kettering Cancer Center (MSKCC), a 2017 Seed Grant Awardee and recent addition to the Hirshberg Foundation’s Scientific Advisory Board, showcased her lab’s research on how cells in a healthy pancreas suppress tumor development in a presentation entitled Identifying stromal barriers to pancreatic tumorigenesis.  

Dr. Sherman’s research focuses on how inflammatory non-tumor cells found in the tumor microenvironment support and aid in tumor growth and progression to potentially target these mechanisms for therapy. One focus of her lab is pancreatic stellate cells (PCSs), a type of stromal cells found in the pancreas. Her previously published work found that when PSCs become activated they regulate and nourish cancer cells to promote tumor growth and progression. Activated PSCs in the tumor microenvironment secrete factors that tumor cells can for growth and survival that can potentially be targeted therapeutically.

Her lab’s more recent research has turned the focus on PSCs in healthy pancreas to identify mechanisms they use to suppress cancer development. A May 2025 publication from her lab demonstrated that in healthy pancreas, PSCs secrete a protein called KITL. In pancreatic tumor models where KITL was genetically deleted, tumors grew earlier than in models with KITL expression and overall survival time was reduced. This work demonstrates the expression of KITL by PSCs is one mechanism by which cells in healthy pancreas are barriers to tumor initiation and progression and identifies a novel pathway for potential therapeutic benefit. Further investigation into other tumor suppressive mechanisms used by healthy tissues and how they break down during tumor initiation and progression may result in identifying other novel therapeutic pathways to explore.

See full publication in Cancer Discovery 

Revolution Medicines announced exciting results on three clinical trials evaluating daraxonrasib, their oral RAS inhibitor, that have the potential to transform treatment options for patients with metastatic pancreatic ductal adenocarcinoma (PDAC). PDAC is the most common type of pancreatic cancer, with a 5-year survival rate of 13%. One reason for this low survival rate is that the majority of patients are diagnosed with advanced, metastatic disease with few treatment options currently available. New treatments with better outcomes for this patient population have the potential to be transformative.

On April 13th, 2026, they shared results from their Phase 3 clinical trial, RASolute 302, demonstrating an unprecedented survival benefit for patients with metastatic PDAC that had previously been treated with chemotherapy. Overall survival (OS) nearly doubled for patients treated with daraxonrasib to 13.2 months compared with 6.7 months for standard-of-care chemotherapy. These data will be presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in June 2026 and will be submitted to the FDA. Approval of daraxonrasib will be a much-needed new treatment for patients with metastatic PDAC who have failed standard chemotherapy and will improve care for patients with this devastating disease.

Results from two additional trials were shared April 21, 2026, at the American Association for Cancer Research (AACR) Annual Meeting. In a presentation in the Minisymposium: Late Breaking Research Session, Dr. Brian Wolpin, MD, MPH, Director of the Hale Family Center for Pancreatic Research at Dana Farber Cancer Institute, shared results from their ongoing Phase 1/2 clinical trial, RMC-GI-102. Patients with newly diagnosed metastatic PDAC were treated with a combination of daraxonrasib with the chemotherapies gemcitabine and nab-paclitaxel. Antitumor activity was demonstrated with 90% of patients showing either stable disease or tumor regression. Additionally,  tumor reduction was seen in 58% of patients with 1 complete response. Importantly, the safety profile was similar to that of each therapy by itself. At 6 months, the progression free survival (PFS) was 84% and OS was 90%.

Preliminary data from RMC-6236-001, a Phase 1/2 clinical trial was also presented. This trial is investigating daraxonrasib as a stand-alone treatment for previously untreated patients with metastatic PDAC. While still early, the disease control rate (DCR) is 92% with an overall response rate of (ORR) of 47% with 1 patient having a complete response. The data from both trials support the recently initiated Phase 3 clinical trial, RASolute 303, evaluating daraxonrasib, alone or in combination with chemotherapy, in newly diagnosed metastatic PDAC patients. 

What is daraxonrasib?

Daraxonrasib is a RAS inhibitor; it binds RAS protein to block its function. RAS has 3 forms: KRAS, NRAS, and HRAS that control cell proliferation and survival. KRASis one of the most frequently mutated genes to cause cancer (see KRAS overview); mutated KRAS is found in more than 90% of PDAC tumors making it an appealing therapeutic target.

Daraxonrasib is a type of drug called a molecular glue; it binds the active form of RAS protein as well as a protein called Cyclophilin A to generate an inactive protein complex. While other RAS inhibitors are specific to the KRAS form of the protein or to specific mutations found in KRAS, daraxonrasib can bind all active forms of RAS, regardless of mutations present, and because of this ability has the potential to treat a range of tumor types outside of PDAC. 

Glossary:

Overall survival (OS):  The length of time from treatment initiation that a patient remains alive. Considered the gold standard for clinical trial endpoints.

Progression-free survival (PFS): The length of time from treatment initiation to when disease progresses. Usually using the RECIST 1.1 criteria for increase in tumor size around 20%. Commonly used as a primary end point in clinical trials 

RECIST 1.1 Criteria: A standardized method for determining disease progression or response in a clinical trial. Tumor size is measured by imaging at the start and then repeated over the course of treatment.  

Complete response (CR): All visible signs of cancer have disappeared due to treatment., frequently measured by imaging. 

Partial response (PR): Tumor size has decreased at least 30% from the initial tumor size but have not completely regressed due to treatment.

Stable disease (SD): When tumors haven’t increased or decreased in size more than 20% of initial tumor size. 

Disease control rate (DCR): The percentage of patients who have stable disease, partial response, or complete response  due to treatment.

Overall response rate (ORR): The percentage of patients who have a response (CR or PR) to treatment based on the RECIST 1.1 criteria. Unlike disease control rate, it does not include patients with stable disease.