Incyte (NASDAQ:INCY) presented updated clinical data and development plans for two experimental solid-tumor programs at ESMO in Madrid: INCA33890, a TGF?R2-by-PD-1 bispecific antibody known as “’890,” and INCB161734, a KRAS G12D-targeted small molecule known as “’734.”
The company said both programs are being advanced into pivotal studies focused initially on gastrointestinal cancers, including microsatellite-stable colorectal cancer and pancreatic ductal adenocarcinoma. Incyte also outlined planned expansion into adjuvant settings and additional combination regimens.
’890 Shows Early Activity in First-Line MSS Colorectal Cancer
Elena Garralda, co-director of the Clinical Research Program at Vall d’Hebron Institute of Oncology, reviewed phase I results for ’890 combined with FOLFOX chemotherapy and bevacizumab in previously untreated microsatellite-stable, or MSS, metastatic colorectal cancer.
Garralda noted that approximately 85% of colorectal cancers are MSS and have not derived substantial benefit from immunotherapy. She described FOLFOX plus bevacizumab as the existing first-line standard of care, with response rates generally around 45% to 50%, median progression-free survival of about 10 months and median overall survival of roughly 25 to 30 months in phase III trials.
Among 42 efficacy-evaluable patients receiving the ’890 combination, the overall response rate was 71%, including a confirmed response rate of 67%. The disease-control rate was 100%, while the six-month progression-free survival rate was 81%, with a median follow-up of nearly six months.
The study population included patients with factors associated with more challenging disease, according to Garralda. Sixty-seven percent of first-line participants had liver metastases, while 63% had KRAS-mutant disease. The response rate was 83% among patients with liver metastases and 62% among those with peritoneal metastases. Patients with PD-L1 expression above 1% had an 81% response rate, compared with 50% among those below 1%, although Garralda cautioned that subgroup sizes were small.
Safety results were generally consistent with expected effects of FOLFOX, bevacizumab and checkpoint inhibition, she said. No dose-limiting toxicities or fatal treatment-related events were observed. The company reported that 14% of patients experienced grade 3 or higher immune-related adverse events.
Steven Stein, Incyte’s chief medical officer and head of late development, said the data support the ongoing phase III NEXERA-303 study. The trial is enrolling 700 previously untreated patients with metastatic MSS colorectal cancer and compares FOLFOX plus bevacizumab with either ’890 or placebo. Its primary endpoint is progression-free survival, with overall survival among key secondary measures. Incyte expects topline results in 2029.
Incyte is also initiating a 40-patient proof-of-concept trial of ’890 in stage II or III colorectal cancer patients who remain circulating tumor DNA-positive after surgery and adjuvant chemotherapy. The study will assess circulating tumor DNA clearance after three months of treatment, among other endpoints.
’734 Data in Pancreatic Cancer and Colorectal Cancer
Manuel Hidalgo, director of the Gastrointestinal Cancer Center at NYU’s Perlmutter Cancer Center, presented phase I data for ’734, which Incyte described as a highly selective KRAS G12D ON/OFF inhibitor. KRAS G12D mutations occur in up to 40% of pancreatic cancers, according to Hidalgo.
In previously untreated advanced pancreatic cancer, ’734 was evaluated with either gemcitabine plus nab-paclitaxel or modified FOLFIRINOX. At recommended dose levels, 26 patients received the gemcitabine/nab-paclitaxel combination and 28 received modified FOLFIRINOX.
The overall response rate was 69% with gemcitabine/nab-paclitaxel and 89% with modified FOLFIRINOX. Confirmed or pending response rates were 58% and 81%, respectively, while disease-control rates approached 100% in both groups. Hidalgo said several complete responses were observed and described them as unusual in this disease setting.
Six-month progression-free survival was about 80% for the gemcitabine/nab-paclitaxel regimen and about 90% for modified FOLFIRINOX. Hidalgo said the progression-free survival and overall survival data remain immature.
Reported adverse events were largely consistent with chemotherapy backbones, with nausea and vomiting identified as additional generally low-grade and manageable side effects associated with ’734. Hidalgo said relative chemotherapy dose intensity was in a range expected for the standard regimens.
Incyte’s phase III DAWN-303 study is enrolling 590 patients with metastatic KRAS G12D-mutated pancreatic ductal adenocarcinoma. The study compares chemotherapy plus ’734 against chemotherapy plus placebo. Overall survival, progression-free survival and objective response rate are primary endpoints. Stein said the company expects topline progression-free survival data in 2028.
In a separate later-line colorectal cancer cohort, ’734 combined with cetuximab produced a 36% response rate and approximately 100% disease control in a small group of patients with KRAS G12D-mutated disease. Median progression-free survival was 7.2 months. Hidalgo contrasted those findings with response rates below 5% for standard later-line approaches discussed during the presentation.
Incyte plans to begin a pivotal second- or third-line colorectal cancer study of ’734 plus cetuximab in the first half of 2027. The company also expects to begin an adjuvant pancreatic cancer phase III program in 2027.
Combination Strategy and Additional Programs
Incyte said it is pursuing additional combinations for ’734, including studies with Bristol Myers Squibb’s PRMT5 inhibitor navlimetostat, Synnovation Therapeutics’ PARP1 inhibitor SNV1521 and Genmab’s petosemtamab. The company said these combination programs are intended to broaden the potential role of ’734 across KRAS G12D-mutated gastrointestinal cancers.
For ’890, Incyte cited ongoing or planned work in ovarian, head and neck, and non-small cell lung cancers, as well as additional combinations involving CTLA-4, EGFR-targeted agents and an antibody-drug conjugate.
Company representatives said the two programs, along with its CDK2 inhibitor ’667 in ovarian cancer, target approximately 250,000 newly diagnosed patients annually across their initially specified indications. Incyte emphasized that both ’890 and ’734 were discovered and developed internally and remain investigational.
About Incyte (NASDAQ:INCY)
Incyte Corporation is a biopharmaceutical company that discovers, develops and commercializes medicines for oncology and inflammatory or autoimmune diseases. The company focuses on therapies that target specific biological pathways, including Janus kinase (JAK), fibroblast growth factor receptor (FGFR) and other mechanisms involved in cancer and immune-related conditions.
Its key products include Jakafi (ruxolitinib), a JAK inhibitor used in the United States for certain blood cancers and graft-versus-host disease; Opzelura (ruxolitinib cream), a topical treatment for atopic dermatitis and nonsegmental vitiligo; and Pemazyre (pemigatinib), an FGFR inhibitor approved for selected patients with cholangiocarcinoma and certain myeloid or lymphoid neoplasms.
