INCB161734 / Incyte - LARVOL DELTA

Preliminary phase 1 results of INCB161734, a novel oral Kirsten rat sarcoma (KRAS) G12D inhibitor, as monotherapy or in combination with chemotherapy for advanced/metastatic pancreatic duct adenocarcinoma (PDAC). (ASCO-GI 2026) - P1 | "Funded by Incyte Corporation Clinical Trial Registration Number: NCT06179160 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Combination therapy • Metastases • Monotherapy • P1 data • Preclinical • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS

A Study to Assess the Effect of Itraconazole, Rifampin, and Acid-Reducing Agents on INCB161734 Pharmacokinetics When Administered Orally in Healthy Participants (clinicaltrials.gov) - P1 | N=63 | Completed | Sponsor: Incyte Corporation | Recruiting ➔ Completed

Trial completion

INCB161734-101: A Study to Evaluate INCB161734 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation (clinicaltrials.gov) - P1 | N=710 | Recruiting | Sponsor: Incyte Corporation | N=466 ➔ 710

Enrollment change • Solid Tumor • KRAS

Data from Incyte’s TGFβR2×PD-1 Bispecific Antibody and KRAS G12D Inhibitor to be Presented at the European Society of Medical Oncology (ESMO) Congress 2025 (Businesswire) - "...Results from Phase 1 proof-of-concept studies of INCA33890, a promising TGFβR2×PD-1-directed bispecific antibody, and INCB161734, a novel, selective and orally bioavailable KRAS G12D inhibitor, will be highlighted as oral presentations..."

P1 data • Solid Tumor

Incyte…announced the first clinical data evaluating its…potent, selective and orally bioavailable KRAS G12D inhibitor (INCB161734) for patients with KRAS G12D mutations, specifically pancreatic ductal adenocarcinoma (PDAC). (Businesswire) - "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%). The study is ongoing for the majority of patients; data on durability of response is expected in the first half of 2026."

P1 data • Pancreatic Ductal Adenocarcinoma

Preliminary phase I results of INCB161734, a novel oral KRAS G12D inhibitor, in patients with advanced or metastatic solid tumors (ESMO 2025) - P1 | "Monotherapy expansion at 600 and 1200 mg qd is ongoing, and combinations with standard therapies in CRC and PDAC are enrolling. Updated data will be presented."

Clinical • Metastases • P1 data • Colorectal Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Sarcoma • Solid Tumor • KRAS

A Study to Assess the Effect of Itraconazole, Rifampin, and Acid-Reducing Agents on INCB161734 Pharmacokinetics When Administered Orally in Healthy Participants (clinicaltrials.gov) - P1 | N=72 | Recruiting | Sponsor: Incyte Corporation | Not yet recruiting ➔ Recruiting

Enrollment open

Incyte...Provides Updates on Key Clinical Programs (Businesswire) - "The Phase 1 data in patients with myelofibrosis (MF) as monotherapy and in combination with ruxolitinib are anticipated in the second half of 2025...A Phase 1 study evaluating JAK2V617Fi in MPNs is ongoing. Initial proof of concept data are anticipated in the first half of 2026...Incyte plans to initiate Phase 3 studies for its potentially first-in-class CDK2 inhibitor (INCB123667), in ovarian cancer in 2025 and is also evaluating INCB123667 in combination with other treatments; The Phase 3 study evaluating tafasitamab as first-line treatment for diffuse large B-cell lymphoma (DLBCL) is ongoing. The Phase 3 data are anticipated in the second half of 2025; The Phase 1 studies evaluating KRASG12D and TGFßR2×PD-1 in solid tumors are ongoing. Initial proof of concept data for both studies are anticipated in the second half of 2025."

Clinical data • New P3 trial • Diffuse Large B Cell Lymphoma • Myelofibrosis • Myeloproliferative Neoplasm • Ovarian Cancer • Solid Tumor

Incyte To Present Initial Data for its TGFβR2×PD-1-directed Bispecific Antibody (INCA33890) and its Selective Inhibitor of G12D-mutated KRAS (INCB161734) at the European Society of Medical Oncology (ESMO) Congress 2025 (Incyte Press Release) - "Details on the abstracts accepted for oral presentation at ESMO include: (i) INCB161734 (KRAS G12D)​: Preliminary Phase 1 Results Of INCB161734, A Novel Oral KRAS G12D Inhibitor, In Patients With Advanced Or Metastatic Solid Tumors​ (...Abstract #916O); (ii) INCA33890 (PD-1/TGFβR2): A Phase 1 Study Of INCA33890, A PD-1/Tgfβr2 Bispecific Antibody, For Advanced Solid Tumours​ (...Abstract #1522); (iii) INCAGN2385 (LAG-3)​: Retifanlimab (Anti–PD-1 Mab) Alone Or In Combination With Anti-LAG3 ± Anti-TIM3 Mabs In Previously Untreated, Recurrent And/Or Metastatic (R/M) PD-L1+ HNSCC: A Double-Blind Randomised Controlled Phase 2 Trial (...Abstract #1325)."

Clinical data • Squamous Cell Carcinoma of Head and Neck

A Study to Assess the Effect of Itraconazole, Rifampin, and Acid-Reducing Agents on INCB161734 Pharmacokinetics When Administered Orally in Healthy Participants (clinicaltrials.gov) - P1 | N=72 | Not yet recruiting | Sponsor: Incyte Corporation

New P1 trial

Incyte Reports 2025 First Quarter Financial Results and Provides Updates on Key Clinical Programs (Businesswire) - "The Phase 3 study evaluating tafasitamab as first-line treatment for DLBCL is ongoing. The Phase 3 data are anticipated in the second half of 2025. The Phase 1 studies evaluating KRASG12D and TGFßR2×PD-1 in solid tumors are ongoing and enrolling patients. Initial proof of concept data for both studies are anticipated in the second half of 2025."

P1 data • P3 data • Diffuse Large B Cell Lymphoma • Solid Tumor

Incyte Reports 2024 Fourth Quarter and Year-End Financial Results, Provides 2025 Financial Guidance and Highlights 2025 R&D Milestones (Businesswire) - "Other Hematology/Oncology – key highlights: Incyte plans to initiate Phase 3 studies for its potentially first-in-class CDK2 inhibitor (INCB123667), in ovarian cancer in 2025 and is also evaluating INCB123667 in combination with other treatments. The Phase 3 study evaluating tafasitamab in first-line DLBCL is ongoing. The Phase 3 data are anticipated in the first half of 2025. The Phase 1 studies evaluating KRASG12D and TGFßR2×PD-1 in solid tumors are ongoing and enrolling patients. Initial proof of concept data for both studies are anticipated in 2025."

New P3 trial • P1 data • P3 data • Diffuse Large B Cell Lymphoma • Ovarian Cancer • Solid Tumor

A Study to Evaluate INCB161734 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation (clinicaltrials.gov) - P1 | N=466 | Recruiting | Sponsor: Incyte Corporation | N=322 ➔ 466

Enrollment change • Metastases • Oncology • Solid Tumor • KRAS

KRAS Mutant Gene Editing Abolishes Tumor Growth In Vivo and Overcomes Acquired Resistance to KRASG12C and KRASG12D Small Molecule Inhibitors (ASGCT 2024) - "Recently, KRASG12C inhibitors (sotorasib,adagrasib) have been approved...KRASG12D inhibitors (MTRX-1133 and INCB161734 ) have recently entered clinical development...We demonstrated a synergistic combination between ADGN-121/Abraxane in pancreatic carcinoma and between ADGN-122/Capecitabine in colon Adenocarcinoma...ADGN-121 containing gRNAG12D/mRNACas9 can overcome MRTX1133 resistance in vitro...ADGN-121, and ADGN-122 were effective in invivo targeting selectively the two major KRAS mutations in G12D and G12V, which are present in 4.2% and 3.6% of all cancer patients respectively. Importantly, ADGN-123 and ADGN-121 constitute a potent alternative strategy to overcome resistance associated to small molecule inhibitors of KRASG12C and KRASG12D"

Preclinical • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

INCB161734: A novel, potent, and orally bioavailable KRAS G12D selective inhibitor demonstrates antitumor activity in KRAS G12D mutant tumors (AACR 2024) - "INCB161734 is efficacious against multiple types of G12D-mutated tumors and xenografts, resulting in significant tumor growth inhibition, growth arrest and/or regression in multiple PDAC (HPAC, Panc0403, and 2838c3) and CRC (CT26, GP2D, and LS513) mouse tumor models.These preclinical results demonstrate that INCB161734 is a potent, selective, and orally bioavailable KRAS G12D inhibitor, strongly efficacious against KRAS G12D mutant tumors. The potential benefit of INCB161734 for patients with KRAS G12D mutant disease is under investigation in ongoing clinical trials."

Colorectal Cancer • Oncology • CASP3 • CASP7 • KRAS

A Study to Evaluate INCB161734 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation (clinicaltrials.gov) - P1 | N=322 | Recruiting | Sponsor: Incyte Corporation | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Oncology • Solid Tumor • KRAS