Incyte Reports Phase 1 Data on TGFβR2×PD-1 Bispecific Antibody in Advanced CRC and KRAS G12D Inhibitor in Advanced PDAC

10/19/2025 – 01:30 PM

• Data presented at ESMO 2025 show INCA33890, a TGFβR2×PD-1 bispecific antibody, has the potential to be an effective treatment in microsatellite stable (MSS) colorectal cancer

• Planned initiation of registrational program for INCA33890 in MSS colorectal cancer in 2026

• Maturing data for INCB161734, a KRAS G12D inhibitor, shows a favorable safety profile and evidence of clinical benefit in heavily pre-treated pancreatic ductal adenocarcinoma (PDAC) patients

• Incyte will expand on the results from the oral presentations at an in-person and webcasted event on Sunday, October 19, 2025, from 1:30 – 3:00 p.m. EDT (7:30 – 9:00 p.m. CEST)

WILMINGTON, Del. – Incyte (Nasdaq:INCY) unveiled compelling clinical data at the European Society of Medical Oncology (ESMO) Congress 2025, highlighting the potential of two novel therapeutic candidates: INCA33890, a TGFβR2×PD-1 bispecific antibody, and INCB161734, a potent, selective, and orally bioavailable KRAS G12D inhibitor. The data, presented in oral sessions, underscore Incyte’s commitment to addressing unmet needs in advanced solid tumors, particularly microsatellite stable (MSS) colorectal cancer and pancreatic ductal adenocarcinoma (PDAC).

“These proof-of-concept data for INCA33890 and INCB161734 represent a significant step forward in our efforts to combat challenging cancers like MSS colorectal cancer and PDAC,” said Pablo J. Cagnoni, M.D., President and Head of Research and Development, Incyte. “The favorable safety profiles observed in monotherapy settings further bolster the rationale for continued clinical development, including exploring combination therapies with current standards of care.”

INCA33890 (TGFβR2×PD-1)

The Phase 1 trial data, presented at ESMO, evaluated INCA33890 as a monotherapy in patients with advanced or metastatic solid tumors, including MSS colorectal cancer, ovarian cancer, squamous cell carcinoma of the head and neck, non-small cell lung cancer, gastric/gastroesophageal junction cancer, and PDAC. The study enrolled patients who had progressed after available therapies or were ineligible for standard treatments, including immune checkpoint inhibitors. Doses ranged from 100 mg to 1,500 mg every two weeks (Q2W) to 900 mg intravenously every four weeks (Q4W). The recommended doses for expansion (RDE) were determined to be 300 mg, 600 mg, and 900 mg Q2W.

Initial data demonstrated promising clinical efficacy and a manageable safety profile. Key observations include:

• A manageable safety profile across all patients (n=260), with immune-related adverse reactions comparable to approved immune checkpoint inhibitors. The most common treatment-related adverse events (TRAEs) were fatigue (13.8%), pruritus (8.8%), and infusion-related reactions (8.4%).
• In a cohort of metastatic MSS colorectal cancer patients (n=105) heavily pre-treated with more than two prior regimens (93.3%) and with active liver metastases (71.4%):
  • 16 patients responded to INCA33890 (14 confirmed), resulting in an objective response rate (ORR) of 15.2% and a median duration of therapy of 7.3 months.
  • ORR was consistent across RDE. Deep tumor responses were observed in patients with liver metastasis (n=9), with an ORR of 12.0% and a disease control rate (DCR) of 20.0%. In patients without liver metastases (n=7), the ORR was 23.3% and DCR was 50.0%.

“The data underscore the potential of INCA33890 to effectively target the TGF-β pathway in MSS colorectal cancer, a particularly challenging subtype of the disease,” said Elena Garralda, M.D., Ph. D., Trial Investigator and Director of Early Drug Development at the Vall d’Hebron Institute of Oncology. “The manageable safety profile further supports its continued development. The bispecific antibody’s mechanism of action, targeting both TGF-β and PD-1, could offer a more comprehensive approach to overcoming tumor-mediated immune suppression.”

Incyte is currently evaluating INCA33890 900 mg Q2W in combination with standard of care (SoC) treatments in patients with MSS colorectal cancer. Dose escalation has been completed without identifying any dose-limiting toxicities (DLTs). The company plans to initiate a registrational program for INCA33890 in MSS colorectal cancer in 2026, signaling a significant commitment to bringing this therapy to market.

INCB161734 (KRAS G12D)

The Phase 1 trial of INCB161734 focused on patients with select advanced or metastatic solid tumors harboring the KRAS G12D mutation, including PDAC, colorectal cancer, NSCLC, OC, and other solid tumors. Patients received varying doses of INCB161734 ranging from 200 mg to 1,600 mg daily. The dose escalation portion of the study is complete, with 600 mg daily and 1,200 mg daily selected for expansion.

Preliminary data demonstrated clinical benefit in heavily pre-treated PDAC patients (n=83). Key findings include:

• A manageable safety profile across all treated patients (n=136). No DLTs were reported in dose escalation, and the maximum tolerated dose (MTD) was not reached. No fatal adverse events (AEs) were considered related to treatment. Common TRAEs included nausea (58.1%), diarrhea (50.7%), vomiting (45.6%), and fatigue (17.4%), mostly Grade 1.
• PDAC patients receiving 600 mg (n=25) and 1,200 mg (n=29) INCB161734 daily demonstrated objective response rates (ORR; 20% and 34%) and high DCRs (64% and 86%). Data on durability of response is expected in the first half of 2026.

“The results with INCB161734 are particularly encouraging in the context of PDAC, a disease with limited treatment options and dismal survival rates,” said Dr. Jayesh Desai, Tiral Investigator, Medical Oncologist and Associate Director of Clinical Research at the Peter MacCallum Cancer Centre. “The observed antitumor activity and strong molecular response in this heavily pretreated patient population suggest that INCB161734 has the potential to become an impactful, selective targeted therapy for PDAC patients carrying the G12D mutation.”

The development of INCB161734 is significant considering the high prevalence of KRAS mutations in various cancers. While KRAS has been a long-sought-after drug target, its smooth, globular structure presented significant challenges for traditional small molecule inhibitors. INCB161734 represents a breakthrough by selectively targeting the G12D mutant form of KRAS, a mutation found in a substantial proportion of PDAC cases.

Based on the initial data, Incyte plans to conduct a comprehensive review to determine the next steps for the INCB161734 program, including initiating discussions with regulatory authorities. The company’s strategic decision-making will likely hinge on continued favorable safety data and the emergence of more mature data on the durability of responses in PDAC patients.

The development of both INCA33890 and INCB161734 underscores Incyte’s strategic focus on developing targeted therapies designed to overcome resistance mechanisms and improve outcomes for patients with difficult-to-treat cancers. The company’s commitment to innovation, coupled with its established expertise in oncology and drug development, positions it to make significant contributions to the field of cancer treatment.

About Incyte

Incyte is a global biopharmaceutical company on a mission to Solve On., Incyte follows the science to find solutions for patients with unmet medical needs. Through the discovery, development and commercialization of proprietary therapeutics, Incyte has established a portfolio of first-in-class medicines for patients and a strong pipeline of products in Oncology and Inflammation & Autoimmunity. Headquartered in Wilmington, Delaware, Incyte has operations in North America, Europe and Asia.

Forward-Looking Statements

This press release contains forward-looking statements that involve risks and uncertainties. Actual results may differ materially from those expressed or implied in such statements due to various factors, including unanticipated delays, the success of further research and development, the ability to enroll sufficient numbers of subjects in clinical trials, determinations made by regulatory authorities, the efficacy and safety of Incyte’s products, market competition, and other risks detailed in Incyte’s filings with the U.S. Securities and Exchange Commission.