Research Highlights from ASCO GI 2026

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The annual American Society of Clinical Oncology Gastrointestinal Cancers Symposium highlighted several new approaches in research and treatment for pancreatic cancer.

The meeting, held from January 8-10, 2026, focused on targeted therapies, such as KRAS G12D inhibitors and degraders, new drugs, and new treatment approaches. Below is just a sampling of some of the exciting trials currently underway. As always, Let’s Win will cover some of these advancements in depth in the coming months.

Targeting KRAS

Treatments targeting KRAS mutations continue to be a significant focus of research.

Preliminary phase I data presented shows that INCB161734, a novel KRAS G12D ON/OFF inhibitor, demonstrates encouraging antitumor activity in advanced and metastatic pancreatic cancer and other solid tumors. In this dose safety and effectiveness study, INCB161734 was tested alone and in combination with the two standard chemotherapy regimens, mFOLFIRINOX and gemcitabine/nab-paclitaxel. Among evaluable patients, the 1,200 mg dose showed a 37 percent objective response rate and 78 percent disease control rate. Early data indicates that combining INCB161734 with either chemotherapy is feasible with manageable safety, allowing for further dose escalation.

Data was presented on another drug targeting KRAS G12D. Setidegrasib (ASP3082) is a KRAS G12D degrader and is being tested alone or in combination with mFOLFIRINOX in patients with previously-treated locally advanced pancreatic cancer or treatment-naïve metastatic disease. The trial includes a dose escalation and expansion cohort of patients who received the novel drug alone, as well as a further cohort of patients who received the recommended phase II dose of 600 mg along with mFOLFIRINOX. According to the researchers, ASP3082 showed promising antitumor activity alone and with mFOLFIRINOX. The findings support continued testing in patients with KRAS G12D-mutant disease in both first-line and later settings.

Novel Drugs and New Treatment Approaches

Adding the investigational drug elraglusib (9-ING-41) to standard first-line gemcitabine and nab-paclitaxel may extend the lives of some patients with metastatic pancreatic cancer, according to phase II data. Among 233 patients with previously untreated disease, the addition of elraglusib to gemcitabine and nab-paclitaxel doubled 12-month overall survival from 22.3 percent to 44.4 percent. Median overall survival improved from 7.2 months with gemcitabine and nab-paclitaxel to 10.1 months with the combination therapy. Elraglusib is a small-molecule inhibitor of glycogen synthase kinase-3 beta designed to disrupt cancer cell survival and combat chemotherapy resistance.

Spevatamig (PT886), a drug targeting claudin 18.2 and CD47, has the potential to be an effective first-line treatment in metastatic pancreatic cancer patients who test positive for the biomarker. Claudin is a protein that normally binds the cells in the stomach. When cancer is present in the stomach or pancreas, the protein appears on the surface of the tumor. Normally CD47 helps protect cells that should be protected. However, cancer cells have a large amount of CD47.

Spevatamig, in combination with chemotherapy, has the potential to be an effective first-line treatment in patients with claudin 18.2 positive metastatic pancreatic cancer. The molecular design of this drug mitigates hematological toxicity, and improves gastrointestinal tolerability, as evidenced by the TWINPEAK study, which includes more than 100 patients in the United States. Early data (2 mg/kg cohort) showed a 40 percent overall response rate, 93 percent disease control rate, and a manageable safety profile.

Platinum-based chemotherapy followed by the combination of durvalumab and olaparib was found to elicit durable antitumor activity in metastatic pancreatic cancer patients with BRCA1, BRCA2, or PALB2 mutations.  In this phase II trial in Spain, the 40 participants achieved a partial or complete response with platinum-based chemotherapy between 2022 and 2024. The primary endpoint was the objective response rate (ORR), with a median follow-up of 11.9 months. There was a 32.5 percent ORR; one patient achieved a complete response, and 12 patients achieved a partial response. The median duration of response was 14.5 months. Overall, the disease control rate with durvalumab plus olaparib was 77.5.

The median progression-free survival (PFS) was 6.7 months, and the PFS rate at 24 months was 22.0 percent. The median overall survival with durvalumab plus olaparib was 15.4 months.

The most frequent adverse events in trial participants included lack of energy, nausea, and anemia. More than a third of patients experienced  adverse events requiring hospitalization. Fifteen percent experienced severe events that may or may not have been related to the drug, the most common of which was anemia.

The OPTIMIZE-1 phase Ib/II study evaluated efficacy and safety of mitazalimab, a human CD40 agonistic IgG1 antibody, in combination with mFOLFIRINOX, in previously untreated patients with metastatic pancreatic cancer. The study met its primary endpoint with promising clinical effectiveness compared to data from older studies of patients treated with just mFOLFIRINOX. The overall response rate was 32.5 percent, with a median duration of response of 14.5 months. Median progression-free survival was 6.7 months, with a 24-month progression-free survival rate of 22.0 percent. The researchers are continuing development of this drug.

In a retrospective study, researchers evaluated the impact of continuous treatment until progression, maintenance therapy, and chemotherapy breaks, in patients with first-line treatment in the Michigan Medicine Optimal Treatment Schedule (MI-OPTS-1) study. There were 183 patients who met these criteria. The researchers concluded the decision to offer breaks or maintenance could potentially be due to differences in group practice, or higher peripheral neuropathy at four months in the chemotherapy break cohort, rather than consideration of health condition in elderly or unfit patients. The patients who received chemotherapy breaks had significantly improved median progression-free survival and overall survival compared to those who had continuous therapy.