Incyte’s KRAS G12D Drug Shows 81% Response Rate in Pancreatic Cancer Trials

Key points

• Incyte’s INCB161734 achieved an 81% confirmed objective response rate and 100% disease control rate in a Phase 1 trial for metastatic pancreatic ductal adenocarcinoma (PDAC) when paired with modified FOLFIRINOX.
• The six-month progression-free survival rate for the modified FOLFIRINOX arm was 90%, while the gemcitabine/nab-paclitaxel arm showed a 58% response rate and 80% six-month progression-free survival.
• Incyte President Pablo Cagnoni stated the company is 'neck and neck' with Revolution Medicines, whose drug zoldonrasib showed an 82% response rate in similar settings, despite Incyte’s drug being an 'ON/OFF' inhibitor versus RevMed’s 'ON' state target.
• The company has launched a global Phase 3 trial (DAWN-303) for first-line metastatic PDAC, with top-line data anticipated in 2028, and plans an adjuvant Phase 3 trial for 2027.
• Incyte also reported data for INCA33890, a bispecific antibody, showing a 71.4% response rate in microsatellite-stable colorectal cancer, and announced new collaborations with Bristol Myers Squibb and Synnovation for pancreatic cancer combinations.

Background

This development follows the FDA approval of Revolution Medicines’ Rasonque earlier in 2026, which validated the potential of RAS-targeting therapies in pancreatic cancer. Recent archive coverage noted that Tango Therapeutics also reported an 82% response rate for a chemo-free combination involving Rasonque at ESMO, highlighting a broader industry shift toward targeted multi-agent therapies in aggressive cancers.

How outlets are covering it

STAT emphasized the strategic importance of these results for Incyte’s future-proofing strategy, noting the impending patent loss of its blockbuster JAK inhibitor Jakafi in 2028. Fierce Biotech focused on the competitive dynamic, quoting Incyte’s leadership as viewing their drug as comparable to Revolution Medicines’ zoldonrasib, with both companies leading the field. Incyte’s press release highlighted the breadth of its portfolio, including new collaborations and data for colorectal cancer, framing INCB161734 and INCA33890 as the foundation of its solid tumor pipeline. While all sources agree on the efficacy data, Fierce Biotech noted the disparity in response rates between chemotherapy arms, which Incyte attributed to the different chemotherapies used rather than the inhibitor itself.

Why it matters

The data supports Incyte’s decision to advance INCB161734 into late-stage trials, potentially establishing a new standard of care for KRAS G12D-mutated pancreatic cancer. With approximately 40% of pancreatic tumors harboring this mutation, the drug’s success could significantly impact treatment options for a high-mortality cancer. The results also intensify competition in the RAS inhibitor space, where multiple companies are racing to develop next-generation therapies that may outperform current standards.

What to watch

Incyte expects top-line data from its Phase 3 DAWN-303 trial in 2028. The company plans to initiate a Phase 3 trial in the adjuvant setting in 2027 and a Phase 3 study in second-line colorectal cancer in the first half of 2027. New Phase 1b trials combining INCB161734 with navlimetostat and SNV1521 are also planned for advanced PDAC.