INCB123667 / Incyte - LARVOL DELTA

Safety and preliminary efficacy from a phase 1 study of INCB123667, a selective CDK2 inhibitor, in patients with advanced platinum-resistant and refractory ovarian cancer (OC). (ASCO 2025) - P1 | "In this phase 1 study of pts with heavily pretreated advanced/metastatic platinum-r/r OC, single agent INCB123667 at various doses showed an acceptable safety profile including expected cytopenia and nausea. The encouraging antitumor activity in this difficult-to-treat population support the advancement of INCB123667 into pivotal studies in pts with platinum-resistant OC."

Clinical • Metastases • P1 data • Platinum resistant • Anemia • Gastrointestinal Disorder • Neutropenia • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor • Thrombocytopenia • CCNE1

Interim safety and antitumor activity data from a phase 1 study of INCB123667, a selective CDK2 inhibitor, in patients with metastatic recurrent endometrial cancer. (ASCO 2025) - P1 | "In this interim analysis, single-agent INCB123667 at various doses has shown an acceptable safety profile in pretreated pts with metastatic recurrent endometrial cancer, including expected cytopenia. The encouraging antitumor activity including post-PD-1 based therapy failure supports future development of INCB123667 in advanced/metastatic endometrial cancer."

Clinical • IO biomarker • Metastases • P1 data • Anemia • Carcinosarcoma • Endometrial Cancer • Neutropenia • Oncology • Pain • Sarcoma • Solid Tumor • Thrombocytopenia • CCNE1

A Study to Evaluate the Effect of Food on the Single-Dose Pharmacokinetics of INCB123667 When Administered Orally to Healthy Adult Participants (clinicaltrials.gov) - P1 | N=15 | Completed | Sponsor: Incyte Corporation | Not yet recruiting ➔ Completed

Trial completion

Incyte to Showcase New Data from its Oncology Portfolio at 2025 American Society of Clinical Oncology (ASCO) Annual Meeting (Businesswire) - "Incyte...that multiple abstracts featuring new data from its oncology portfolio will be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 30 – June 3, 2025, in Chicago."

Clinical data • Platinum resistant • Anal Squamous Cell Carcinoma • Endometrial Cancer • Glioblastoma • Merkel Cell Carcinoma • Myelofibrosis • Ovarian Cancer

A Study to Evaluate the Effect of Food on the Single-Dose Pharmacokinetics of INCB123667 When Administered Orally to Healthy Adult Participants (clinicaltrials.gov) - P1 | N=15 | Not yet recruiting | Sponsor: Incyte Corporation

New P1 trial

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

INCB 123667-101: Study of INCB123667 in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=604 | Recruiting | Sponsor: Incyte Corporation | N=340 ➔ 604 | Trial primary completion date: Apr 2024 ➔ Aug 2025

Enrollment change • Monotherapy • Trial primary completion date • Breast Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Safety and tolerability of INCB123667, a selective CDK2 inhibitor, in patients (pts) with advanced solid tumors: A phase I study (ESMO 2024) - P1 | "INCB123667 was generally well tolerated with promising antitumor activity in pts with cyclin E1 overexpressing or CCNE1 amplified advanced/metastatic solid tumors. Dose expansion is ongoing in 6 tumor-specific cohorts. Evaluation of INCB123667 combination tx has been planned."

Clinical • Metastases • P1 data • Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • CCNE1

Incyte’s CDK2 Inhibitor INCB123667 Shows Promising Evidence of Clinical Activity in Patients with Advanced Solid Tumors, Notably Ovarian Cancer (Businesswire) - P1 | N=340 | NCT05238922 | Sponsor: Incyte Corporation | "New data from the Phase 1b dose expansion portion of the trial (data cut-off August 26, 2024) presented today during Incyte’s investor event....Of the 37 evaluable participants with platinum-resistant ovarian cancer treated at three (3) selected dose levels (50mg BID, 100mg QD and 125mg QD) in the expansion portion of the trial, nine participants (24.3%) experienced an overall response (OR; 2 complete responses [CR] and 7 partial responses [PRs]). The highest OR rate of 31.3% (5 responders, including 2 CRs) was found in the 50mg BID cohort (16 evaluable participants)....Results from the Part 1a dose escalation portion of the trial (data cut-off July 15, 2024) include: INCB123667 demonstrated a manageable safety profile (n=84)....Strong selective inhibition of CDK2 was observed resulting in circulating tumor DNA (ctDNA) reduction at all dose levels."

P1 data • Endometrial Cancer • Gastrointestinal Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Ovarian Cancer • Triple Negative Breast Cancer

Incyte to Present Late-Breaking Phase 3 Results for Retifanlimab (Zynyz) and Initial Data from Phase 1 CDK2 Inhibitor Program at the European Society of Medical Oncology (ESMO) Congress 2024 (Businesswire) - "Incyte...announced that the Company will present key data from its oncology portfolio at the upcoming European Society of Medical Oncology (ESMO) Congress 2024, to be held September 13-17 in Barcelona and virtually....'Notably, a Presidential Symposium will feature new, pivotal results from the Phase 3 POD1UM-303/InterAACT2 study of retifanlimab (Zynyz) for the treatment of squamous cell anal carcinoma (SCAC). The POD1UM-303 data will support the supplemental Biologics License Application (sBLA) filing for retifanlimab in SCAC planned by year end 2024'...We will also present new data on INCB123667, a potential first-in-class CDK2 inhibitor, which we believe has the potential to enhance outcomes and serve as a foundational treatment for platinum-resistant ovarian and other cancers.'"

FDA filing • P1 data • P3 data • Anal Carcinoma • Oncology • Solid Tumor • Squamous Cell Carcinoma

Incyte Reports 2023 Fourth Quarter and Year-End Financial Results, Provides 2024 Financial Guidance and Highlights R&D Priorities (Businesswire) - P1 | N=340 | NCT05238922 | Sponsor: Incyte Corporation | "JAK2V617Fi (INCB160058), a potent and selective JAK2 pseudokinase domain binder, cleared the Investigational New Drug (IND) process with the FDA and a Phase 1 study is anticipated to initiate in the first half of 2024. In January 2024, Incyte highlighted promising early clinical efficacy data for its selective small molecule inhibitor of CDK2 (INCB123667), which demonstrated its potential use as monotherapy or combination therapy for late-stage cancers. In a Phase 1 study of INCB123667, early clinical activity was observed with several partial responses (PR) achieved in patients with amplification/over expression of CCNE1, a cell cycle regulator and potential predictive biomarker. Tumor shrinkage was observed across multiple tumor types, including CCNE1+ patients with ovarian cancer. The safety profile of for INCB123667 aligns with the mechanism of action. Additional data is expected to be presented in 2024."

IND • New P1 trial • P1 data • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

Incyte Highlights Growth Opportunities and Provides Business Updates at the 42nd Annual J.P. Morgan Healthcare Conference (Businesswire) - "Additionally, the Company will highlight progress across its Oncology pipeline and the research it is advancing in areas of high potential, including promising early clinical efficacy data for INCB123667, a potent and selective inhibitor of CDK2, demonstrating its potential use as monotherapy or combination therapy for late-stage cancers."

P1 data • Oncology • Solid Tumor

Study of INCB123667 in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=340 | Recruiting | Sponsor: Incyte Corporation | N=250 ➔ 340

Enrollment change • Metastases • Monotherapy • Breast Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Incyte Reports 2023 First Quarter Financial Results and Provides Updates on Key Clinical Programs (Businesswire) - "At AACR, Incyte presented data demonstrating INCB123667 exhibited significant single-agent activity in vivo in CCNE1high breast cancer xenograft and patient-derived xenograft models....Preclinical in vivo data presented at AACR show that INCA33890 has a greater anti-tumor effect than either individual benchmark antibodies or a simple combination of these."

Preclinical • Breast Cancer • Oncology • Solid Tumor

Study of INCB123667 in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=250 | Recruiting | Sponsor: Incyte Corporation | N=155 ➔ 250

Enrollment change • Breast Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Development of a CDK2-selective small molecule inhibitor INCB123667 for the treatment of CCNE1hi breast cancers (AACR 2023) - "Treatment resulted in cell growth inhibition and antitumor activity in vitro and in vivo. Our data demonstrate the therapeutic potential of CDK2 inhibition in CCNE1hi HR+ HER2− and TNBC breast cancer models.Acknowledgments: R&D services provided by Pharmaron, Crown Bioscience, and Champions Oncology"

Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CCNE1 • CDK1 • CDK2 • CDK7 • CDK9 • ER • HER-2

Discovery of INCB123667, a potent and selective cyclin-dependent kinase 2 (CDK2) inhibitor for the treatment of cyclin E dysregulated cancers (AACR-NCI-EORTC 2022) - "Our data indicate that INCB123667 is a selective and potent CDK2 kinase inhibitor that has antitumor activity in cyclin E-overexpressing cancers and tumor xenograft models. These preclinical findings support the ongoing clinical evaluation of INCB123667 as a CDK2-selective inhibitor for the treatment of cancer."

Breast Cancer • Eye Cancer • Oncology • Ovarian Cancer • Retinoblastoma • Solid Tumor • CDK1 • CDK7 • CDK9

Study of INCB123667 in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=155 | Recruiting | Sponsor: Incyte Corporation | Trial primary completion date: May 2025 ➔ Apr 2024

Monotherapy • Trial primary completion date • Breast Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Study of INCB123667 in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=155 | Recruiting | Sponsor: Incyte Corporation | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy • Breast Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor