GT Biopharma Explores KRAS Inhibitor Combination Following Positive Pancreatic Cancer Study Results

GT Biopharma is exploring the potential of combining its investigational natural killer (NK) cell engager GTB-5550 with KRAS inhibitors following encouraging preclinical findings in pancreatic cancer models.

The clinical-stage immuno-oncology company presented the new data at the Society for Immunotherapy of Cancer (SITC) 2026 Annual Meeting, held November 4-8 in Phoenix, AZ. The research evaluated whether GTB-5550, developed using the company’s proprietary TriKE® platform, could enhance the antitumor activity of KRAS inhibitors.

The findings come as researchers increasingly investigate combination approaches to address a key limitation of KRAS-targeted therapies: the development of resistance. Although RAS inhibitors have made significant progress in treating certain cancers, tumor cells can activate alternative signaling pathways that allow them to evade treatment. Combining targeted therapies with other mechanisms of antitumor activity could help produce more sustained responses.

In preclinical orthotopic patient-derived pancreatic ductal adenocarcinoma (PDAC) xenograft models, treatment with GTB-5550 alongside a KRAS inhibitor produced stronger tumor control than KRAS inhibition alone. Researchers reported complete tumor clearance in several animals, along with reductions in local tumor invasion and the prevention of metastatic spread.

The combination also resulted in approximately twice the level of tumor infiltration compared with KRAS inhibitor monotherapy. Additional findings included greater persistence of adoptively transferred NK cells and increased expression of CXCR3, a receptor associated with immune cell trafficking. Researchers also observed elevated markers of apoptosis in tumor cells, suggesting greater tumor cell death with the combination treatment.

GT Biopharma said the results support further investigation of GTB-5550 as a potential partner for targeted therapies in pancreatic cancer.

“We continue to make progress enrolling patients into our ongoing Phase 1a/1b dose-escalation basket trial with GTB-5550 across multiple tumor types,” says Michael Breen, executive chairman and CEO of GT Biopharma.

Breen adds that, in light of recent advances in KRAS-targeted treatments and the new preclinical findings, the company is evaluating options for a future Phase 1b study combining GTB-5550 with a KRAS inhibitor in patients with pancreatic cancer.

The proposed combination would bring together targeted inhibition of cancer-driving mutations with GT Biopharma’s approach to harnessing NK cells, potentially addressing resistance mechanisms that can limit the effectiveness of KRAS inhibitors.

For more information, visit www.gtbiopharma.com.