Pancreatic ductal adenocarcinoma (PDAC) has been the textbook hard-to-treat cancer: median overall survival in the metastatic setting has hovered around 6–12 months for two decades. Over 90% of PDACs carry a mutation in KRAS — long considered "undruggable" until the first KRAS G12C inhibitors (sotorasib, adagrasib) reached FDA approval in lung cancer in 2021–2022. But the G12C variant is rare in PDAC (~1–2%); the dominant PDAC variants are G12D (~40%), G12V (~30%), and G12R (~15%) — all of which the G12C-only inhibitors miss.
Two things have changed that landscape in the past 18 months:
ASCO 2026 is the first major conference where the Phase 3 program is fully visible. Here's what to watch.
NCT07491445 is the registrational Phase 3 testing daraxonrasib as monotherapy and daraxonrasib + gemcitabine/nab-paclitaxel (GnP) versus standard-of-care chemotherapy in patients with metastatic PDAC who have not had prior treatment for advanced disease. This is the trial that, if positive, could move the front-line PDAC standard for the first time in a decade.
NCT07252232 tests daraxonrasib versus standard-of-care observation as adjuvant treatment after surgical resection of PDAC. The fact that Revolution Medicines launched a Phase 3 in both the metastatic AND adjuvant settings simultaneously is unusual and reflects high confidence in the Phase 1/2 RMC-6236-001 data.
NCT05379985 is the original Phase 1/2 of daraxonrasib in advanced solid tumors with RAS mutations. Updated data from this study — especially in PDAC subgroups by mutation variant — is widely anticipated at ASCO and ESMO.
NCT06128551 tests elironrasib (RMC-6291, G12C-selective) and daraxonrasib as monotherapies and combination therapy in patients with KRAS G12C-mutated solid tumors. The combination of variant-selective + pan-RAS is a novel approach — the variant-selective drug provides depth of inhibition, the pan-RAS drug provides breadth against resistance mutations that arise after G12C-only therapy.
G12D is the dominant KRAS variant in PDAC (~40%), so G12D-selective therapy has the largest addressable patient population in pancreatic cancer:
NCT07349537 — RMC-5127 in KRAS G12V-mutant solid tumors. G12V is the second-most-common PDAC KRAS variant (~30%).
NCT07066098 is a Phase 3 of IBI343 (an antibody-drug conjugate targeting claudin 18.2) versus placebo in patients with CLDN18.2-positive PDAC that has progressed after prior therapy. Claudin 18.2 is expressed in ~60% of PDAC — a much broader target than any single KRAS variant. ADC technology brings a chemotherapy payload directly to claudin 18.2-positive cells, which limits systemic toxicity.
Spevatamig (PT886) is a bispecific antibody targeting both claudin 18.2 and FGFR2b. NCT05482893 (Phanes Therapeutics) is enrolling PDAC, gastric, GEJ, and biliary patients in a Phase 1/2 dose-escalation + expansion design with combination arms (spevatamig + paclitaxel/gemcitabine; spevatamig + pembrolizumab + oxaliplatin). Notable: ASCO 2026 should bring early efficacy signals on the bispecific approach in this group.
NCT06953999 is a 3-arm Phase 3 (Akeso) in first-line metastatic PDAC: ivonescimab (a PD-1 × VEGF bispecific antibody) + AK117 (anti-CD47) + GnP chemo, vs ivonescimab + AK117 placebo + GnP, vs double placebo + GnP. The design tests both whether ivonescimab adds benefit over chemo alone AND whether AK117 add-on adds further benefit. Pancreatic cancer is notoriously immune-cold, so the PD-1/VEGF bispecific approach is mechanistically attractive: the VEGF arm normalizes tumor vasculature to help immune cells reach the tumor, and the PD-1 arm unleashes them once they arrive.
NCT07562152 — atebimetinib + gemcitabine/nab-paclitaxel as first-line metastatic PDAC. The -metinib stem suffix is typically reserved for MEK1/2 inhibitors (trametinib, binimetinib, cobimetinib, selumetinib); MEK is downstream of RAS in the MAPK pathway. Targeting MEK in combination with chemotherapy is a long-standing PDAC strategy that has previously underperformed, but newer agents plus better patient selection (KRAS-mutant enrichment) may produce different results. Confirm the specific mechanism with your oncologist before considering this trial.
About 5–7% of PDAC patients carry a germline BRCA1, BRCA2, or PALB2 mutation, which makes the tumor sensitive to platinum chemotherapy and PARP inhibitors. The PLATINUM-CAN trial (NCT06783140, Phase 2/3) tests NABPLAGEM (nab-paclitaxel + cisplatin + gemcitabine) versus nab-paclitaxel/gemcitabine alone in BRCA1/2 or PALB2-mutated metastatic PDAC as second-line treatment after progression on first-line FOLFIRINOX. The hypothesis: adding cisplatin to the gold-standard GnP regimen will improve outcomes for HRD-positive patients specifically after first-line failure. NCT06095141 takes a different approach — cisplatin in patients with documented homologous recombination deficiency, independent of germline status.
This makes germline + somatic genetic testing more important than ever for PDAC patients. If you have a family history of breast, ovarian, prostate, or pancreatic cancer, ask your oncologist whether germline testing has been done.
Pancreatic cancer causes some of the most severe weight loss and muscle wasting of any malignancy (cachexia), which itself reduces survival and quality of life. Pfizer's NCT06989437 is a combined Phase 2/3 of ponsegromab (a GDF-15 antagonist) in PDAC patients with cachexia — the first dedicated registrational program of a GDF-15 antagonist in pancreatic cancer cachexia. (Anamorelin, a ghrelin-receptor agonist with a different mechanism, was studied in the ROMANA program in lung + colorectal + pancreatic cancers and is approved in Japan for cachexia in those cancers since 2021.) Earlier ponsegromab Phase 2 data (announced 2024, Groarke et al., NEJM) showed clinically meaningful weight gain. If the Phase 3 portion confirms, this could become an important supportive-care option for a symptom that has been undertreatable for decades.
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Find Matching TrialsThis page is for information only and is not medical advice. ClinTrialFinder helps you find clinical trials that may match your situation, but enrollment decisions and treatment choices should always be made with your oncologist or healthcare team. Trial eligibility, recruitment status, and treatment details can change — verify directly with the trial sponsor or on ClinicalTrials.gov before acting on any information here. ASCO 2026 may surface additional data not yet reflected on this page; check the trial registry for the most current status.