Incyte Presents Updated Clinical Data for KRAS G12D and TGFβR2×PD-1 Programs in Pancreatic and Colorectal Cancers
Incyte has announced new clinical findings from its expanding oncology portfolio, highlighting the potential of two investigational cancer therapies in difficult-to-treat pancreatic and colorectal cancers. The updated data cover INCB161734, a KRAS G12D inhibitor being evaluated in pancreatic ductal adenocarcinoma (PDAC) and advanced or metastatic colorectal cancer (CRC), and INCA338901, a TGFβR2×PD-1 bispecific antibody being investigated in microsatellite stable colorectal cancer (MSS CRC).
The findings were presented in three rapid oral sessions at the European Society for Medical Oncology (ESMO) Congress 2026. The presentations included updated Phase 1 results for INCB161734 in patients with KRAS G12D-mutated pancreatic cancer, clinical activity and safety data for the same investigational drug in advanced or metastatic colorectal cancer, and preliminary findings for INCA33890 in patients with MSS CRC receiving combinations with standard-of-care therapies.
The results provide additional evidence of clinical activity across multiple treatment settings and combinations. In pancreatic cancer, INCB161734 demonstrated encouraging response rates when combined with established chemotherapy regimens. In colorectal cancer, the investigational KRAS G12D inhibitor showed activity both as a monotherapy and in combination with cetuximab. Meanwhile, INCA33890 produced promising preliminary responses when added to standard treatment regimens for MSS CRC, including among patients with liver and peritoneal metastases.
Pablo J. Cagnoni, M.D., President of Incyte and Global Head of Research and Development, said the company remains focused on improving outcomes for people living with cancer. He noted that the findings for INCB161734 and INCA33890 highlight the potential of both programs to improve treatment options for patients with challenging malignancies.
According to Cagnoni, the company continues to observe encouraging clinical activity and manageable safety profiles across pancreatic and colorectal cancers, supporting further development across tumor types and lines of therapy. He also described the two programs as emerging foundations of Incyte’s growing solid tumor portfolio, with the potential to address significant unmet medical needs.
INCB161734 Shows Encouraging Activity in Metastatic Pancreatic Cancer
INCB161734 is an investigational inhibitor targeting KRAS G12D, a mutation being explored as a therapeutic target in several cancers. Incyte presented updated Phase 1 findings evaluating the drug in combination with two standard-of-care chemotherapy regimens in patients with metastatic pancreatic ductal adenocarcinoma carrying a documented KRAS G12D mutation.
The data cutoff was July 6, 2026, and the analysis included 54 patients treated with INCB161734 at a dose of 1,200 mg once daily. The drug was administered with either gemcitabine plus nab-paclitaxel, known as GEMNabP, or modified FOLFIRINOX, referred to as mFOLFIRINOX.
The results indicated substantial antitumor activity with both combinations, alongside safety findings that Incyte described as manageable and broadly consistent with the established safety profiles of the chemotherapy regimens.
INCB161734 Plus mFOLFIRINOX
Among patients receiving INCB161734 with mFOLFIRINOX, the objective response rate (ORR) was reported as 89% when confirmed and pending responses were included, while the confirmed-only response rate was 81%. The disease control rate (DCR) reached 100%, indicating that all patients in the reported group achieved either a tumor response or disease stabilization under the study’s assessment.
The six-month landmark progression-free survival (PFS) rate was 90%. PFS measures the length of time patients live without their cancer progressing or dying, while a landmark PFS rate describes the proportion of patients who remain progression-free at a specified time point. The six-month result offers an early indication of disease control, although longer follow-up will be needed to establish the durability of benefit.
The median treatment duration for patients receiving the combination was six months. Incyte also reported that no treatment-related adverse events led to discontinuation of INCB161734 in this group.
The most frequently reported treatment-related adverse events (TRAEs) were diarrhea, occurring in 68% of patients; nausea, in 64%; vomiting, in 57%; and decreased neutrophil count, also in 57%.
These gastrointestinal and blood-count-related events are important considerations when combining an investigational targeted therapy with intensive chemotherapy. Incyte reported that gastrointestinal treatment-related adverse events were predominantly Grade 1 or Grade 2 and improved during treatment.
INCB161734 Plus GEMNabP
The second combination, INCB161734 plus gemcitabine and nab-paclitaxel, also produced encouraging results in patients with metastatic PDAC.
The ORR was 69% when confirmed and pending responses were included, compared with 58% for confirmed responses alone. The DCR was 96%, indicating broad disease control among patients treated with the combination.
The six-month landmark PFS rate was 80%, while the median treatment duration was seven months. One patient discontinued INCB161734 because of treatment-related adverse events, which Incyte characterized as a low discontinuation rate.
The most common TRAEs were diarrhea, nausea and decreased neutrophil count, each reported in 65% of patients. Anemia occurred in 58%.
Across both treatment groups, the company said INCB161734 was tolerable when administered with chemotherapy. The overall safety and tolerability profile was broadly consistent with the known profiles of the standard-of-care regimens, and most gastrointestinal adverse events were low grade and improved over the course of treatment.
The findings are preliminary and come from an early-stage clinical study. Nevertheless, the response rates and six-month PFS results support continued investigation of INCB161734 in metastatic pancreatic cancer, where treatment options remain limited and durable disease control is challenging to achieve.
Phase 3 Development Plans for Pancreatic Cancer
Incyte is advancing INCB161734 into later-stage clinical development to further evaluate its potential in pancreatic cancer. The global Phase 3 DAWN-303 study is underway and is evaluating INCB161734 in combination with investigator-selected standard-of-care chemotherapy in patients with first-line metastatic PDAC.
The study will assess the investigational therapy alongside either GEMNabP or mFOLFIRINOX, building on the clinical activity and safety findings reported in the Phase 1 analysis. Incyte anticipates topline results from DAWN-303 in 2028.
The company is also planning a Phase 3 study in the adjuvant setting for pancreatic cancer in 2027. Adjuvant treatment is administered after primary treatment, such as surgery, with the aim of reducing the risk of cancer recurrence. Evaluating INCB161734 in this setting would extend its development beyond metastatic disease and explore whether KRAS G12D inhibition could provide benefits earlier in the treatment pathway.
In addition, Incyte plans two Phase 1b clinical collaborations to investigate novel combinations involving INCB161734 in advanced or metastatic PDAC.
One planned study will combine INCB161734 with navlimetostat, Bristol Myers Squibb’s MTA-cooperative PRMT5 inhibitor. A second planned Phase 1b trial will evaluate INCB161734 alongside SNV1521, Synnovation’s PARP1 inhibitor.
These studies are intended to explore additional combination approaches for patients with advanced pancreatic cancer. Their progress will help determine whether combining KRAS G12D inhibition with other targeted mechanisms can expand treatment options. Further clinical data will be required to establish the safety, efficacy and appropriate patient populations for these investigational combinations.
INCB161734 Demonstrates Activity in Advanced or Metastatic Colorectal Cancer
Incyte also presented new Phase 1 results for INCB161734 in advanced or metastatic colorectal cancer carrying a KRAS G12D mutation. The analysis, with a data cutoff of July 6, 2026, included 49 patients and evaluated the investigational drug at 1,200 mg once daily as a monotherapy and in combination with cetuximab.
The findings showed antitumor activity and a manageable safety profile, supporting further evaluation of the treatment in patients whose disease has progressed following previous therapies.
Among heavily pretreated patients who received INCB161734 in combination with cetuximab, the reported ORR was 36% and the DCR was 100%. Median PFS was 7.2 months, with a reported 95% confidence interval of 5.4 months to not estimable (NE).
The ORR represents the proportion of patients whose tumors shrink by a predefined amount following treatment, while the DCR includes patients who experience either a response or stable disease. The reported results suggest that the combination demonstrated disease-control activity in this heavily pretreated population. However, the findings come from an early-stage study and will require confirmation through further clinical evaluation.
The safety analysis covered INCB161734 administered alone and in combination with cetuximab. The monotherapy group included 24 patients, while the combination group included 25 patients in the reported safety analysis. In the combination dose-escalation phase, no dose-limiting toxicities were observed, and a maximum tolerated dose was not reached.
Incyte also reported low rates of treatment-related adverse events leading to treatment discontinuation or dose modification across the monotherapy and combination groups. These findings support continued dose evaluation and further investigation of INCB161734 in this patient population.
Cetuximab is an established targeted therapy used in certain colorectal cancer treatment settings. Its evaluation alongside INCB161734 reflects the company’s strategy of investigating the KRAS G12D inhibitor in combination with other anticancer therapies.
Planned Phase 3 Study in Previously Treated CRC
Incyte expects to initiate the Phase 3 DAWN-302 study in the first half of 2027. The trial will evaluate INCB161734 in combination with cetuximab in patients with previously treated metastatic colorectal cancer.
The planned study represents an important step toward determining whether the activity observed in Phase 1 can translate into meaningful clinical benefit in a larger patient population. The results will also help establish the potential role of the combination in the treatment sequence for patients with KRAS G12D-mutated disease.
Beyond DAWN-302, Incyte is continuing to investigate the potential of INCB161734 through ongoing and planned studies designed to explore resistance mechanisms and additional treatment strategies.
These efforts include an ongoing study evaluating INCB161734 with cetuximab and standard-of-care chemotherapy in first-line metastatic colorectal cancer. The company is also pursuing a tumor-agnostic cohort, which is intended to investigate treatment potential across cancer types rather than limiting enrollment to a single tumor location.
Incyte has previously announced a collaboration with Genmab in colorectal cancer. Together, the planned and ongoing investigations reflect a broader effort to determine how KRAS G12D inhibition might be used across different disease stages, combination regimens and tumor settings.
INCA33890 Shows Preliminary Efficacy in Microsatellite Stable CRC
The third presentation at ESMO 2026 focused on INCA33890, an investigational TGFβR2×PD-1 bispecific antibody being studied in microsatellite stable colorectal cancer.
MSS CRC is a particularly challenging disease setting in which many patients have limited benefit from existing immunotherapy approaches. Incyte is evaluating INCA33890 in combination with standard treatments to assess whether targeting TGFβR2 and PD-1 together can improve antitumor activity.
The updated Phase 1 analysis included 94 patients, with a data cutoff of August 26, 2026. Patients received INCA33890 at a dose of 900 mg intravenously every two weeks in combination with different standard-of-care therapies.
The combinations included bevacizumab alone, FOLFOX plus bevacizumab, FOLFIRI plus bevacizumab, or cetuximab. FOLFOX and FOLFIRI are chemotherapy regimens used in colorectal cancer, while bevacizumab targets vascular endothelial growth factor and cetuximab targets the epidermal growth factor receptor.
The results showed encouraging preliminary efficacy across the evaluated cohorts and selected patient subgroups, with a manageable safety profile reported by the company.
First-Line Combination Produces a 71% Response Rate
The most notable results were reported in the first-line setting among patients receiving INCA33890 in combination with FOLFOX and bevacizumab.
In the reported analysis, this treatment group included 42 patients and achieved an ORR of 71% and a DCR of 100%. The six-month PFS rate was 81%.
These findings indicate that the combination demonstrated substantial preliminary antitumor activity in the studied population. The six-month PFS result also suggests that a considerable proportion of patients remained free from disease progression at that landmark. Further follow-up and controlled clinical studies will be necessary to determine the duration of benefit and the treatment’s comparative effectiveness.
Responses were observed among patients with different patterns of metastatic disease. In patients with liver metastases, the ORR was 83%, with responses recorded in 24 of 29 patients. Among patients with peritoneal metastases, the ORR was 62%, with responses recorded in eight of 13 patients.
The company also reported an ORR of 81% among patients whose tumors had a programmed death-ligand 1 (PD-L1) tumor area positivity (TAP) score of at least 1%. This result was observed in 21 of 26 patients in the subgroup.
The findings across these subgroups are noteworthy because metastatic colorectal cancer can involve different disease distributions, and patient characteristics may influence treatment outcomes. However, the subgroup sizes were relatively small, and the results should be considered preliminary rather than definitive evidence of efficacy in any specific subgroup.
Safety Findings and Treatment Discontinuations
The most common treatment-emergent adverse events (TEAEs) in the first-line treatment setting were neuropathy, reported in 77% of patients; neutropenia, in 58%; and stomatitis, in 47%.
Treatment-emergent adverse events are events that occur after treatment begins and are not necessarily caused by the investigational drug. The reported findings therefore describe events observed during treatment rather than establishing that INCA33890 directly caused every event.
Treatment discontinuation was reported in four patients, representing 9% of the group. Incyte stated that combinations of INCA33890 with standard-of-care therapies were tolerable and that no dose-limiting toxicities were observed.
Because INCA33890 was administered with chemotherapy and other established agents, ongoing assessment of tolerability will be important in determining the contribution of each treatment to the overall safety profile. Additional data from larger trials will be needed to clarify the balance of potential benefits and risks.
Phase 3 and Adjuvant Studies Continue
Incyte is advancing INCA33890 through the global Phase 3 NEXERA-303 study. The trial is evaluating INCA33890 in combination with FOLFOX and bevacizumab as a first-line treatment for patients with MSS CRC. Topline results are expected in 2029.
The company is also conducting a Phase 2 study of INCA33890 in the adjuvant setting for MSS CRC following chemotherapy. This investigation will explore the potential role of the bispecific antibody after initial treatment, extending its development beyond advanced disease.
Together, these studies are designed to provide a more comprehensive assessment of INCA33890’s clinical potential, including its effectiveness when combined with established therapies and its possible role at different stages of colorectal cancer management.
Investor Event and Webcast
Incyte said the data presented during the ESMO oral sessions would be discussed at an in-person analyst and investor event on Monday, October 26, 2026, from 7:30 p.m. to 9:00 p.m. Central European Time, corresponding to 2:30 p.m. to 4:00 p.m. Eastern Daylight Time.
The event will also be available by webcast through the Events and Presentations section of the Investor area on Incyte’s corporate website. A replay is expected to remain available for 30 days.
Further information about the ESMO Congress 2026 and Incyte’s presentations is available on the official ESMO Congress website.
Expanding Incyte’s Solid Tumor Pipeline
The three presentations highlight Incyte’s efforts to advance investigational treatments for pancreatic and colorectal cancers, two disease areas where the need for more effective treatment options remains significant.
INCB161734 has demonstrated encouraging preliminary activity when combined with chemotherapy in metastatic pancreatic cancer and when administered alone or with cetuximab in advanced or metastatic colorectal cancer. Meanwhile, INCA33890 has produced promising early findings in MSS CRC, including a 71% ORR in the reported first-line combination group receiving FOLFOX and bevacizumab.
The programs are at different stages of clinical development, with Phase 3 studies underway or planned for both investigational therapies. Upcoming results will be important in determining whether the early signals translate into sustained clinical benefit and support future treatment options.
Although the findings are encouraging, the reported results are based largely on early-stage studies and preliminary analyses. Larger clinical trials and longer follow-up will be needed to establish the efficacy, durability and safety of these investigational approaches. Incyte’s ongoing studies will help clarify their potential roles in treating patients with KRAS G12D-mutated pancreatic and colorectal cancers and microsatellite stable colorectal cancer.
About INCB161734
INCB161734 is an investigational, novel, selective and orally bioavailable small molecule ON/OFF KRAS G12D inhibitor. KRAS is one of the most frequently altered oncogenic drivers across solid tumors, and the KRAS G12D mutation is among the most common KRAS alterations, occurring in approximately 40% of pancreatic ductal adenocarcinoma (PDAC) cases and approximately 15% of colorectal cancer (CRC) cases.
INCB161734 is being evaluated in the global Phase 3 DAWN-303 (NCT07522073) study which is currently enrolling patients with previously untreated KRAS G12D-mutated PDAC to further evaluate the efficacy and safety of INCB161734 in combination with standard-of-care (SoC) chemotherapy. Incyte will also be initiating the Phase 3 DAWN-302 study evaluating INCB161734 in combination with cetuximab in patients with previously treated metastatic colorectal cancer.
INCB161734 is also being evaluated as a monotherapy and in combination SoC chemotherapy (gemcitabine/nab-paclitaxel [GEMNabP] or modified FOLFIRINOX [mFOLFIRINOX]), in an ongoing open-label Phase 1 study across KRAS G12D-mutated solid tumors (NCT06179160).
About INCA33890
INCA33890 is an investigational, TGFβR2×PD-1 bispecific antibody, developed in collaboration with Merus (now part of Genmab) using their Biclonics® antibody platform, engineered to block TGF-β–mediated signaling in immune cells co-expressing TGF-βR2 and PD-1. TGFβ is known to promote cancer immune evasion and predicts poor response to PD-(L)1 targeted therapies.
INCA33890 aims to spare tissues where TGF-β signaling is important for normal function, avoiding the known toxicity of a broad blocking of the TGF-β pathway. INCA33890 offers a novel, promising, potentially first-in-class targeted treatment strategy for patients with advanced or metastatic solid tumors, including microsatellite stable colorectal cancer (MSS CRC).2,3,4,5
INCA33890 is being evaluated in a Phase 1 study (NCT05836324) in patients with advanced or metastatic solid tumors. It is also being evaluated in Phase 2 and Phase 3 studies, including the Phase 2 NEXERA-204 study (NCT07823322) assessing INCA33890 monotherapy for the treatment of circulating tumor DNA-positive stage 2/3 MSS CRC after curative resection and chemotherapy. Additionally, the Phase 3 NEXERA-303 study (NCT07284849) evaluating the efficacy and safety of INCA33890 in combination with FOLFOX and bevacizumab for patients with previously untreated metastatic MSS CRC is currently enrolling.
About Incyte
Incyte is redefining what’s possible in biopharmaceutical innovation. Through deep scientific expertise and a relentless focus on patients, we have built an established portfolio of first-in-class medicines and an extensive portfolio of next-generation medicines across our key franchises: Hematology, Oncology, and Inflammation and Autoimmunity.