June 17, 2026
For decades, pancreatic cancer has defied nearly every major therapeutic advance in oncology. Five-year survival rates hovered in the low single digits, and conference after conference brought negative trial results. Now, two landmark developments are giving researchers and patients new reasons for optimism.
"This is a burgeoning era in drug development in pancreatic cancer," says Hani M. Babiker, M.D., a physician-scientist focused on pancreatic cancer and early-phase oncology at Mayo Clinic Comprehensive Cancer Center in Jacksonville, Florida. Dr. Babiker was centrally involved in both advances. "We are seeing evidence that we're headed in the right direction in our efforts to fight this cancer."
Daraxonrasib: Finally inhibiting KRAS
One of the most promising developments involves daraxonrasib, formerly RMC-6236, which is an oral KRAS-targeted therapy studied in the phase 3 RASolute 302 trial.
More than 90% of pancreatic cancers contain KRAS mutations that drive tumor growth. For decades, attempts to inhibit KRAS failed because the protein's structure left few opportunities for drugs to bind effectively.
"It's a very smooth protein without any pockets to target," Dr. Babiker says. "And it binds extremely tightly to GTP, the on-switch for KRAS signaling. That makes it difficult for drugs to interrupt the signaling process."
Daraxonrasib takes a fundamentally different approach. Rather than targeting a pocket, the oral agent acts as a molecular "glue," using a cyclophilin chaperone to inhibit signaling across multiple KRAS subtypes. This mechanism blocks KRAS from activating RAF and triggering the downstream signaling that drives cancer cell proliferation.
"The results of the phase 3 RASolute 302 trial are striking," Dr. Babiker says. "Daraxonrasib demonstrated a median overall survival of 13.2 months compared with 6.7 months for chemotherapy. And it did so with an oral tablet rather than combination intravenous chemotherapy."
Mayo Clinic was among the study's highest-accruing sites nationally across all three campuses, with Mayo Clinic in Florida playing a particularly active role. The U.S. Food and Drug Administration (FDA) recently granted daraxonrasib a Commissioner's National Priority Voucher designation intended to accelerate potential review and availability. Frontline and perioperative studies are already underway, and scientists are investigating combination approaches with other novel agents.
FDA approval for tumor treating fields (TTFields)
Another recent advance comes from an entirely different direction. In February 2026, the FDA approved TTFields combined with chemotherapy for patients with unresectable locally advanced pancreatic adenocarcinoma (LA-PAC).
Approval was based on findings from the PANOVA-3 trial, a global, randomized phase 3 study conducted across 20 countries and 198 sites. The trial randomized patients with LA-PAC to gemcitabine and nab-paclitaxel chemotherapy with or without TTFields. The PANOVA-3 trial results were published in the Journal of Clinical Oncology.
PANOVA-3 showed improvements in overall survival, distant progression-free survival, pain deterioration and time to opioid use. The therapy also improved several quality-of-life measures.
TTFields delivers low-intensity electrical fields through arrays placed on the skin. The noninvasive therapy inhibits cancer cell proliferation, alters tumor permeability to improve drug delivery and changes the tumor microenvironment. And it may enhance tumor immunogenicity.
Dr. Babiker first became interested in the technology more than a decade ago after seeing its success in glioblastoma. His laboratory at Mayo Clinic in Florida later studied TTFields in pancreatic cancer models before the therapy advanced into larger clinical trials.
Dr. Babiker, who served as the global principal investigator for PANOVA-3 and chaired the international steering committee, notes that the approval addresses a long-standing care gap.
"About 80% of patients present with advanced disease, and more than half of them have tumors that cannot be surgically removed because they involve major blood vessels," he says. "This is the first positive randomized trial for this patient subset. Historically, it's been an area with tremendous unmet need and very few advances, so seeing a positive trial in this setting is extremely encouraging."
Researchers continue to evaluate how TTFields may work in combination with other systemic therapies. Mayo Clinic in Florida is currently prescribing TTFields in clinic. An investigator-initiated trial combining the therapy with platinum and gemcitabine and nab-paclitaxel has completed accrual with results anticipated later this year.
Partnership that leads to better outcomes
Mayo Clinic in Florida offers patients a subspecialized, high-volume program built around multidisciplinary expertise.
The pancreatic cancer team includes medical oncologists, surgical oncologists, radiation oncologists, gastroenterologists, interventional radiologists, genetic specialists, nutritionists, palliative care teams and social workers. Physicians regularly review cases in multidisciplinary tumor boards to determine the best treatment strategy for each patient.
"Our team is subspecialized and focused on this disease," Dr. Babiker says. "We think outside the box to pursue every possible treatment option for our patients."
The Florida campus has expanded its pancreatic cancer referral base significantly in recent years and draws patients from across the United States and internationally. Its clinical trials portfolio spans phases 1 through 3, and gives eligible patients access to therapies unavailable elsewhere.
A turning point
Despite the recent momentum in pancreatic cancer research, Dr. Babiker stresses that substantial unmet needs remain. Pancreatic cancer incidence continues to rise, including among younger adults.
Still, after years of stalled progress, he believes the field has entered a new phase.
"This is only the beginning," Dr. Babiker says. "In partnership with Mayo colleagues and community oncologists, we can achieve a great deal to help patients and families now and in the future who are facing this aggressive disease."
For more information
Babiker HM, et al. Tumor treating fields with gemcitabine and nab-paclitaxel for locally advanced pancreatic adenocarcinoma: Randomized, open-label, pivotal phase III PANOVA-3 study. Journal of Clinical Oncology. 2025;43:2350.
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