Slides
Page 1
Domenica Lorusso,1 Silvia Damian,2 Kosei Hasegawa,3 Kaissa Ouali,4 Matteo Simonelli,5 Ingrid Boere,6 Marcia Cruz Correa,7 Carlos Alberto Gomez-Roca,8 Shigehisa Kitano,9 Edward Wang,10 Jason Howe,11 Calvin Jia,11 Michelle Kinder,11 Louis Viviers,12 Vanda Salutari13 Presentation number 1241RO Preliminary Efficacy of INCB123667 (CDK2 Inhibition) With Bevacizumab in Recurrent Epithelial Ovarian Cancer (rEOC) 1Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome and Humanitas San Pio X, Milan, Italy; 2Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; 3Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Saitama, Japan; 4Institut Gustave Roussy, Villejuif, France; 5IRCCS Humanitas Research Hospital, Rozzano, Italy; Humanitas University, Pieve Emanuele, Italy; 6Erasmus MC Cancer Institute, Rotterdam, Netherlands; 7PanOncology Trials, University of Puerto Rico, Oncologic Hospital Dr. Isaac González Martínez, San Juan, Puerto Rico; 8Institut Universitaire du Cancer de Toulouse (IUCT) – Oncopole, Toulouse, France; 9Department of Advanced Medical Development, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan; 10Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, USA; 11Incyte Corporation, Wilmington, DE, USA; 12Incyte Biosciences International, Morges, Switzerland; 13Policlinico Universitario Fondazione Agostino Gemelli, Rome, Italy
Page 2
Content of this presentation is copyright and responsibility of the author. Permission is required for re-use. Disclosures • Lorusso: Consultant – Novartis, PharmaMar. Advisory board and invited speaker – AstraZeneca, Clovis Oncology, Corcept, Genmab, GSK, Immunogen, MSD, Seagen, Sutro. Coordinator for ENGOT trial with institutional support – Clovis Oncology, Corcept, Genmab, MSD, Immunogen. Received grant for founding academic trial – Clovis Oncology, GSK, MSD
Page 3
Content of this presentation is copyright and responsibility of the author. Permission is required for re-use. Introduction • The CDK2/Cyclin E1 complex is crucial for cell-cycle progression and DNA replication1 • Cyclin E1 overexpression identifies a poor prognostic subgroup of patients with OC who derive less benefit from SoC therapies and have a high unmet need for new treatments2-7 • INCB123667 is a novel, selective, oral small-molecule CDK2 inhibitor • INCB123667 monotherapy (50 mg bid) demonstrated a manageable safety profile and an ORR of 31% in patients with PROC treated in an ongoing phase 1 study (NCT05238922)8 • Combination treatment with INCB123667 + bevacizumab in a CCNE1-amplified OC model resulted in enhanced inhibition of tumour growth compared with either agent alone9 Figure used with permission of EUREKA SCIENCE (FZC), from D’Mello SR, Chin PC. Treating neurodegenerative conditions through the understanding of neuronal apoptosis. Curr Drug T argets CNS Neurol Disord. 2005;4:3-23. Copyright© 2005 Bentham Science Publishers Ltd; permission conveyed through Copyright Clearance Center, Inc. 1. Siu KT, et al. Cell Cycle. 2012;11:57-64. 2. Aziz D, et al. Gynecol Oncol. 2018;151:327-336. 3. Kang EY, et al. Cancer. 2023;129:697-713. 4. Rosen DG, et al. Cancer. 2006;106:1925-1932. 5. Kim D, et al. NPJ Precis Oncol. 2026;10:244. 6. Etemadmoghadam D, et al. Clin Cancer Res. 2009;15:1417‐1427. 7. Nakayama N, et al. Cancer. 2010;116:2621‐2634. 8. Lorusso D, et al. ESMO 2025. Presentation 974P. 9. Incyte Corporation. Data on file. bid, twice a day; CDK, cyclin-dependent kinase; OC, ovarian cancer; ORR, objective response rate; PROC, platinum-resistant or platinum-refractory ovarian cancer; RB, retinoblastoma protein; SoC, standard of care. INCB123667 G1 M/G1 checkpoint G2/M checkpoint G1/S checkpoint P P P PRB RBE2F E2FM Cell cycle Cyclin A CDK2 Cyclin E CDK1 Cyclin B CDK1 Cyclin A CDK4/6 Cyclin D G2 G0 phase (resting) Transcription of cell cycle and apoptotic genes CDK2
Page 4
Content of this presentation is copyright and responsibility of the author. Permission is required for re-use. Study Design • INCB123667 is being evaluated in combination with anticancer therapies in a phase 1, open-label, multicentre, dose escalation and dose expansion study (NCT05238922) in patients with advanced solid tumours • Here, we report preliminary phase 1 efficacy and safety data from patients with PROC who received INCB123667 + bevacizumab *Dose escalation tumours were HR+/HER2− breast cancer (regardless of CCNE1 mutation/cyclin E1 overexpression status) or other solid tumours (documented CCNE1 amp/cyclin E1 overexpression preferred but not mandatory). †CCNE1 amp determined by a qualified local laboratory or cyclin E1 overexpression determined by central laboratory (CLIA assay). ‡Dose escalation started 1 dose level below the highest dose demonstrated to be safe in the monotherapy part of the study for INCB123667 combinations with bevacizumab, olaparib and paclitaxel, and 2 dose levels below the highest dose demonstrated to be safe for the monotherapy part of the study for INCB123667 combinations with palbociclib and ribociclib.1 All patients with PROC were treated with INCB123667 50 mg bid + bevacizumab 10 mg/kg q2w IV in dose escalation/expansion. §Continuous 28-day cycles. Bevacizumab is administered until disease progression, unacceptable toxicity or 15 months of treatment have been received. 1. Lorusso D, et al. ESMO 2025. Presentation 974P. amp, amplification; bid, twice a day; CLIA, chemiluminescent immunoassay; DCR, disease control rate; DLT, dose-limiting toxicity; DOR, duration of response; HR, hormone receptor; IV, intravenously; ORR, objective response rate; PK, pharmacokinetics; PO, orally; PROC, platinum-resistant or platinum-refractory ovarian cancer; q2w, every 2 weeks; SoC, standard of care. Key Eligibility Criteria Dose Escalation • Any advanced/metastatic solid tumour* • Progressed on or ineligible/intolerant to SoC • CCNE1 amp not mandatory but preferred Dose Expansion • Advanced/metastatic epithelial ovarian, fallopian, or primary peritoneal carcinoma • Prior first-line platinum-taxane chemotherapy • CCNE1 amp or cyclin E1 overexpression required† • Number of prior lines of therapy was not limited Secondary Endpoints • ORR, DCR, DOR • PK Primary Endpoints • Safety and tolerability • DLTs Bevacizumab§ (10 mg/kg q2w IV) Paclitaxel Palbociclib Ribociclib Olaparib INCB123667 (50 mg bid PO) combination cohorts Dose escalation and dose expansion‡
Page 5
Content of this presentation is copyright and responsibility of the author. Permission is required for re-use. Baseline Disease Characteristics Data cutoff: July 30, 2026. *Including patients with PROC who received INCB123667 50 mg bid orally + bevacizumab 10 mg/kg q2w intravenously in dose escalation (n=3) and dose expansion (n=20). †Data derived from NeoGenomics, August 24, 2026. ‡CCNE amplification status was based on a local test result (n=5) and where not available or not amplified locally, on the central test result using cell-free DNA. §Due to sample quantity not sufficient for analysis. bid, twice a day; BRCA, breast cancer gene; ECOG PS, European Cooperative Oncology Group performance status; HRD, homologous recombination deficien cy; PARPi, poly(ADP-ribose) polymerase inhibitor; PD, progressive disease; PROC, platinum-resistant or platinum-refractory ovarian cancer; q2w, every 2 weeks. Total (N=23) Patient and Disease Characteristics* Age, median (range), years 60 (45, 78) ECOG PS, n (%) 0 17 (73.9) 1 6 (26.1) Tumour histology, n (%) Serous 18 (78.3) High-grade serous 14/18 (77.8) Clear cell 3 (13.0) Mucinous 1 (4.3) Carcinosarcoma 1 (4.3) Primary platinum-free interval, n (%) <3 months 2 (8.7) 3-6 months 5 (21.7) >6 months 16 (69.6) Last platinum-free interval ≤6 months, n (%) 23 (100) Total (N=23) Prior Therapies* Number of prior lines of therapy, n (%) 1-2 8 (34.8) 3 5 (21.7) ≥4 10 (43.5) Prior bevacizumab, n (%) 19 (82.6) Prior PARPi, n (%) 15 (65.2) PD during PARPi treatment 14/15 (93.3) Biomarkers* Cyclin E1 overexpression,† n (%) 20 (87.0) CCNE1 amplification‡ 7/20 (35.0) CCNE1 amplification not detected‡ 13/20 (65.0) Cyclin E1 expression unknown,§ n (%) 3 (13.0) CCNE1 amplification‡ 1/3 (33.3) CCNE1 amplification not detected‡ 2/3 (66.7) HRD positive 7 (30.4) BRCA mutation 7/7 (100) HRD negative 5 (21.7) HRD unknown 11 (47.8)
Page 6
Content of this presentation is copyright and responsibility of the author. Permission is required for re-use. Preliminary Efficacy in PROC • Median follow-up was 7.4 months • ORR 48% (95% CI: 27, 69); confirmed ORR 43% (95% CI: 23, 66) — 10 of 11 patients had a confirmed response – Prior PD with PARPi (n=14): ORR 43% (95% CI: 18, 71) – Prior bevacizumab (n=19): ORR 42% (95% CI: 20, 67); confirmed ORR 37% (95% CI: 16, 62) • DCR 91% (95% CI: 72, 99) • Median DOR 5.7 months (95% CI: 3.7, 9.4); median PFS 7.4 months (95% CI: 5.7, 9.3) *Including RECIST-evaluable patients with PROC who received INCB123667 50 mg bid orally + bevacizumab 10 mg/kg q2w intravenously in dose escalation and dose expansion. RECIST-evaluable patients had a baseline scan and met at least 1 of the following criteria: ≥1 postbaseline scan, ≥63 days of treatment or study discontinuation. bid, twice a day; CI, confidence interval; DCR, disease control rate; DOR, duration of response; EOT, end of treatment; ORR, objective response rate; PARPi, poly(ADP-ribose) polymerase inhibitor; PD, progressive disease; PFS, progression-free survival; PR, partial response; PROC, platinum-resistant or platinum-refractory ovarian cancer; RECIST, Response Evaluation Criteria In Solid Tumours; SD, stable disease; q2w, every 2 weeks. Best Percentage Change From Baseline in Sum of Target Lesions, % –100 100 80 PD 20 –30 PD SD SD SD SD SD SD SD SD SD SD PR PR PR PR PR PR PR PR PR PR PR 60 40 20 0 –20 –40 –60 –80 Dose escalation Dose expansion PR SD PD PD at EOT Ongoing Death PARPi discontinuation due to PD Prior bevacizumab 0 50 100 150 200 250 300 350 Days 400 450 500 550 600 650 700 Dose escalation Dose expansion
Page 7
Content of this presentation is copyright and responsibility of the author. Permission is required for re-use. • The median (range) duration of exposure was 7.6 (1.9, 16.9) months for INCB123667 + bevacizumab • Any-grade INCB123667-related TEAEs occurred in 23 (100%) patients – 18 (78%) had a bevacizumab-related TEAE • Grade 3 treatment-related AEs occurred in 12 (52%) patients • Grade 4 treatment-related AEs occurred in 1 patient (thrombocytopenia) • Grade 5 TEAE occurred in 1 patient (sepsis, not considered to be related to treatment) • SAEs occurred in 4 patients (17%) and were treatment-related in 1 patient (4%) – SAEs were colitis, constipation, intestinal obstruction*, sepsis, and small intestinal obstruction (n=1 each) • No patients discontinued INCB123667 due to TEAEs • 2 patients discontinued bevacizumab due to TEAEs (fistula and proteinuria, n=1 each) *Related to INCB123667. AE, adverse event; GGT, gamma-glutamyltransferase; SAE, serious adverse event; TEAE, treatment-emergent adverse event. Any-Grade TEAEs,† n (%) Total (N=23) Anaemia 16 (69.6) Constipation 11 (47.8) Neutropenia 11 (47.8) Nausea 10 (43.5) Hypertension 9 (39.1) Thrombocytopenia 9 (39.1) Abdominal pain 7 (30.4) Leukopenia 7 (30.4) Proteinuria 7 (30.4) Vomiting 7 (30.4) Arthralgia 6 (26.1) Asthenia 6 (26.1) Oedema, peripheral 6 (26.1) Diarrhoea 5 (21.7) Hypercholesterolaemia 5 (21.7) Grade 3 TEAEs,‡ n (%) Total (N=23) Proteinuria 5 (21.7) Intestinal obstruction 3 (13.0) Neutropenia 3 (13.0) Asthenia 2 (8.7) Fatigue 2 (8.7) GGT increased 2 (8.7) Leukopenia 2 (8.7) †Occurring in ≥5 patients. ‡Other grade 3 TEAEs occurring in 1 patient: abdominal pain, anaemia, blood alkaline phosphatase increased, colitis, constipation, diarrhoea, hyperamylasaemia, hyperbilirubinaemia, hypercholesterolaemia, hyperlipasaemia, hypertension, hypertriglyceridaemia, hypoalbuminaemia, hypokalaemia, hyponatraemia, nausea, oedema peripheral, pain in extremity, peripheral sensory neuropathy, sepsis, small intestinal obstruction, thrombocytopenia, vomiting. Safety Outcomes
Page 8
Content of this presentation is copyright and responsibility of the author. Permission is required for re-use. Conclusions DCR, disease control rate; DOR, duration of response; EOC, epithelial ovarian cancer; ORR, objective response rate; PFS, progression-free survival; PROC, platinum-resistant or platinum-refractory ovarian cancer; TEAE, treatment-emergent adverse event. • INCB123667, a novel, selective, oral small-molecule CDK2 inhibitor, in combination with bevacizumab showed promising antitumour activity in heavily pretreated patients with PROC and cyclin E1-overexpression – Preliminary results report an ORR of 48%, a DCR of 91%, a median DOR of 5.7 months, and a median PFS of 7.4 months • INCB123667 + bevacizumab was well tolerated and TEAEs were manageable – The most common TEAEs were anaemia (70%), constipation (48%) and neutropenia (48%), which were mostly low grade – No patients discontinued INCB123667 due to TEAEs; 2 patients discontinued bevacizumab • A phase 3 study of INCB123667 + bevacizumab vs bevacizumab alone as first-line maintenance therapy in patients with EOC with cyclin E1 overexpression will commence in 2026 (MAESTRA3; NCT07797283)
Page 9
European Society for Medical Oncology (ESMO) Via Ginevra 4, CH-6900 Lugano T. +41 (0)91 973 19 00 esmo@esmo.org esmo.org • The authors wish to thank the patients and their families, the investigators, and the site personnel who participated in this study • This study was sponsored by Incyte Corporation (Wilmington, DE, USA) • Medical writing support was provided by Alasdair Gunn, DPhil, of Envision Medical Communications, and funded by Incyte Corporation To download a copy of this presentation, scan code. Copies of this presentation obtained through the QR code are for personal use only and may not be reproduced without written permission of the authors.