What is a clinical trial?

A clinical trial is a research study involving human participants designed to evaluate medical interventions — such as drugs, devices, or behavioral strategies. Trials follow a structured protocol and are registered on ClinicalTrials.gov. They progress through phases: Phase 1 (safety), Phase 2 (efficacy), Phase 3 (large-scale comparison), and Phase 4 (post-market surveillance).

How do I find clinical trials I'm eligible for?

You can search ClinicalTrials.gov or use ClinicalMetric to filter by condition, phase, or location. Each trial listing includes eligibility criteria such as age range, sex, diagnosis, and prior treatment history. Contact the study team directly or ask your physician to refer you to a relevant trial.

Are clinical trials safe to participate in?

Clinical trials are conducted under strict ethical and regulatory oversight, including IRB approval and FDA regulation in the US. All participants must give informed consent after reviewing potential risks and benefits. Phase 1 trials carry more uncertainty, while Phase 3 trials involve interventions with an established safety profile. Participation is always voluntary and you may withdraw at any time.

What are the phases of clinical trials?

Clinical trials progress through four main phases. Phase 1 tests safety and dosing in a small group (20–80 people). Phase 2 evaluates efficacy and side effects in a larger group (100–300). Phase 3 compares the intervention against standard treatments in thousands of participants. Phase 4 occurs after approval and monitors long-term effects in the general population.

Do participants get paid for joining clinical trials?

Many clinical trials offer compensation for time and travel expenses, though payment structures vary widely by study. Compensation is not intended to be coercive. Some trials also cover treatment costs for participants. Always review the consent form carefully and ask the study coordinator about any financial considerations before enrolling.

Pancreatic Cancer Clinical Trials 2026: KRAS Inhibitors, Immunotherapy, and New Treatments

Medical Notice

This article is for informational purposes only and does not constitute medical advice. Clinical trial eligibility and availability vary. Always consult a qualified oncologist before making any treatment decisions or considering participation in a clinical trial.

Summary

Pancreatic ductal adenocarcinoma (PDAC) remains one of oncology's most difficult challenges — with a 5-year survival rate of approximately 13% for all stages combined, it is the third leading cause of cancer-related death in the United States. However, 2026 represents a genuinely pivotal moment: KRAS G12D inhibitors are entering Phase 2 trials after years of KRAS being considered "undruggable," personalized mRNA cancer vaccines are showing early efficacy signals in Phase 2, and liquid biopsy is enabling earlier detection in high-risk individuals. With over 800 active pancreatic cancer clinical trials on ClinicalTrials.gov, patients at all stages of disease have more options than at any previous point. This guide covers the most important trials recruiting in 2026, molecular testing requirements, and how to find a study.

Why Pancreatic Cancer Has Been Difficult to Treat

PDAC is characterized by a dense stromal (fibrous tissue) environment that physically excludes immune cells and limits drug delivery, late-stage diagnosis in over 80% of patients, and near-universal activating mutations in KRAS that drive tumor growth. For decades, KRAS was considered undruggable because its structure offered no obvious binding pocket for small-molecule inhibitors. The breakthrough with sotorasib (KRAS G12C) in lung cancer opened a new era, but KRAS G12C is rare in pancreatic cancer — KRAS G12D is the dominant mutation (approximately 40% of PDAC cases), and targeting G12D required different chemistry.

Additionally, PDAC does not respond to checkpoint inhibitor immunotherapy (anti-PD-1/PD-L1) in the way that cancers like melanoma or lung cancer do — the immunosuppressive microenvironment and low mutational burden render these drugs largely ineffective as single agents. Combination strategies to "heat up" the tumor microenvironment before adding immunotherapy are a major 2026 research theme.

KRAS G12D Inhibitors: The Most Anticipated Trials

After the success of sotorasib and adagrasib against KRAS G12C mutations in lung cancer, the field turned to KRAS G12D — which affects approximately 40% of pancreatic cancer patients. Several KRAS G12D inhibitors are now in clinical trials.

MRTX1133 (Mirati/BMS): The most advanced KRAS G12D selective inhibitor; Phase 1/2 trial (NCT05737706) is recruiting patients with KRAS G12D-mutant solid tumors including pancreatic cancer. Early data shows encouraging single-agent activity in PDAC.
HRS-4642 (Heurigen): Oral KRAS G12D inhibitor in Phase 1 with pancreatic cancer expansion cohorts; combination with chemotherapy is planned for 2026.
Requirement: All KRAS G12D inhibitor trials require tumor molecular profiling confirming KRAS G12D mutation — patients must have recent tissue or liquid biopsy results.
Pan-KRAS inhibitors: BI 1701963 and RMC-6236 (RAS(ON) multi-selective) target multiple KRAS mutations simultaneously and may offer options for patients with KRAS G12V or other non-G12D mutations.

mRNA Personalized Cancer Vaccines

Moderna/Merck's mRNA-4157/V940 personalized cancer vaccine generates a custom neoantigen vaccine based on sequencing each patient's tumor. In the KEYNOTE-942 trial for resected melanoma, the vaccine plus pembrolizumab reduced recurrence by 44% compared to pembrolizumab alone — a landmark result that triggered Phase 3 trials across multiple tumor types.

Pancreatic cancer Phase 2: The mRNA-4157 vaccine is being evaluated in the adjuvant setting (after surgery for resectable PDAC) in combination with pembrolizumab and mFOLFIRINOX chemotherapy — enrollment ongoing at major cancer centers.
Process: Requires surgery with sufficient tumor tissue for sequencing; vaccine manufacture takes approximately 6–8 weeks; treatment begins approximately 9–12 weeks post-surgery.
BioNTech BNT122: A competing individualized neoantigen vaccine in Phase 2 for resected PDAC (IMCODE003); results from early patients showing immune responses.

CAR-T and Cellular Therapies for Solid Tumors

CAR-T cell therapy, which has transformed blood cancer treatment, faces significant challenges in solid tumors including PDAC — the immunosuppressive microenvironment, antigen heterogeneity, and physical barriers limit T-cell trafficking. However, several approaches are showing promise in early trials.

Mesothelin-targeted CAR-T: Mesothelin is highly expressed on pancreatic cancer cells; multiple Phase 1 trials are evaluating anti-mesothelin CAR-T alone and with checkpoint inhibitors or chemotherapy conditioning.
TIL (Tumor-Infiltrating Lymphocyte) therapy: Lifileucel (Amtagvi), FDA-approved for melanoma in 2024, is being studied in pancreatic cancer; PDAC TIL expansion protocols are in development.
Bispecific T-cell engagers: Molecules that simultaneously bind a tumor antigen and CD3 on T-cells; programs targeting CEA, HER2-low, and mesothelin are in Phase 1 for PDAC.

Chemotherapy Combinations and Nanoparticle Delivery

While targeted therapies advance, chemotherapy remains the backbone of PDAC treatment. Gemcitabine plus nab-paclitaxel and FOLFIRINOX remain standard first-line regimens. Active 2026 trials are testing novel combinations:

NALIRIFOX: Liposomal irinotecan + oxaliplatin + fluorouracil (NALIRIFOX regimen) was FDA-approved in 2023 and is now standard first-line for metastatic PDAC; ongoing AMPLIFY-201 trial tests it with anti-PD-1.
Hyaluronidase (PEGPH20): Degrades the hyaluronan barrier in PDAC stroma; combination with nab-paclitaxel/gemcitabine trials ongoing after mixed Phase 3 results prompt refined patient selection.
PARP inhibitors: Olaparib maintenance is standard for BRCA1/2-mutant metastatic PDAC (about 5–7% of patients) following the POLO trial; trials testing PARP + ATR inhibitor combinations for BRCA-wild-type patients.

Early Detection Trials in High-Risk Individuals

For individuals at high hereditary risk (BRCA1/2, PALB2, ATM mutations; familial pancreatic cancer; Peutz-Jeghers syndrome; Lynch syndrome), surveillance and early detection trials offer an important option before cancer develops.

CAPS (Cancer of the Pancreas Screening) consortium studies: Endoscopic ultrasound and MRI/MRCP surveillance protocols for high-risk individuals — ongoing multi-center studies tracking detection rates.
Liquid biopsy early detection: GRAIL Galleri multi-cancer early detection test and competitive platforms are being validated in prospective trials including NHS-Galleri (140,000 UK participants); pancreatic cancer is a key target given how well liquid biopsy signals correlate with early disease.
CA19-9 biomarker studies: Trials optimizing the use of CA19-9 in combination with imaging for earlier diagnosis in average-risk individuals with diabetes of new onset.

How to Find Pancreatic Cancer Trials in 2026

ClinicalTrials.gov: Search "pancreatic cancer" + "recruiting" — filter by phase and location. Request your complete molecular profiling results first (KRAS mutation subtype matters).
Pancreatic Cancer Action Network (PanCAN): PanCAN's Patient Services team provides free, personalized clinical trial matching — they maintain relationships with trial coordinators and can identify studies not yet widely publicized.
NCI-designated cancer centers: These institutions run the largest pancreatic cancer research programs and have access to the most trials; seeking a consultation even if you receive primary care elsewhere can open trial access.
Molecular profiling: Ensure comprehensive genomic profiling (Foundation One CDx or similar) — not just KRAS G12D, but BRCA1/2, PALB2, ATM, NTRK fusions, TMB, and mismatch repair status, all of which determine trial eligibility.

End of Guide // ClinicalMetric Intelligence — CM-INS-072