A first-in-human (FIH), Phase 1/2, dose-escalation and dose-optimization study of central nervous system (CNS)-penetrant, PARP1-selective inhibitor EIK1004 in patients with advanced solid tumors with or without brain metastases
Presenter: Meghal Gandhi Session: Phase I and Phase II Clinical Trials in Progress Time: 4/21/2026 2:00:00 PM → 4/21/2026 5:00:00 PM
Authors
Timothy A. Yap 1 , Jian Zhang 2 , Yanhua Xu 3 , Sanum Chaudry 4 , Kevin H. Eng 4 , Yawei Zhang 4 , Viola J. Chen 4 , Gerald Falchook 5 1 University of Texas MD Anderson Cancer Center, Houston, TX, 2 Fudan University Shanghai Cancer Center, Shanghai, China, 3 Impact Therapeutics, Shanghai, China, 4 Eikon Therapeutics, Jersey City, NJ, 5 Sarah Cannon Research Institute at HealthONE, Denver, CO
Abstract
Background: PARP inhibitors (PARPi) selectively kill tumor cells harboring genetic mutations in critical DNA repair genes (e.g., BRCA1/2). Approved nonselective PARPi have demonstrated robust antitumor activity, but are associated with significant hematologic toxicities that limit dose intensity and clinical benefit. Drugs that selectively inhibit PARP1, but spare PARP2, may improve the risk-benefit profile by retaining antitumor activity while avoiding PARP2-related toxicities. Furthermore, current PARPi have variable brain penetrance, limiting their utility for targeting CNS tumors or brain metastases. EIK1004 (IMP1707) is a potent, CNS-penetrant, PARP1-selective inhibitor that demonstrates tumor growth inhibition in preclinical brain metastasis models. Methods: Study EIK1004-001 (IMP1707-101) is a FIH, global, multi-center, Phase 1/2 study evaluating the safety and potential antitumor activity of EIK1004 monotherapy in patients with advanced ovarian, breast, prostate, or pancreatic cancer, with or without brain metastases (NCT06907043). The study consists of Part 1 (Dose Escalation; using the Bayesian optimal interval [BOIN] design) and Part 2 (Dose Optimization). All participants must have a deleterious or suspected deleterious mutation in select homologous recombination repair genes and received no more than one prior line of PARPi treatment. Eligible participants must be ≥ 18 years, have histologically or cytologically confirmed tumors and received appropriate prior antitumor therapies, and have evaluable disease (eg, at least 1 measurable lesion by RECIST 1.1 [or RANO-BM for brain metastases] and/or serum tumor markers). Primary endpoints include safety and tolerability including identifying the maximum tolerated dose or maximum achievable dose, and recommended dose(s) for expansion (RDE). Secondary endpoints include evaluation of EIK1004 pharmacokinetics and preliminary antitumor activity including overall response, duration of response, and progression-free survival. Part 2 will open once the RDE is determined from Part 1. This study opened on 23-Jan-2025 and is actively enrolling participants.
Disclosure
T. A. Yap, University of Texas MD Anderson Cancer Center Employment, g., Board of Directors, non-salaried role), ). AbbVie; Acrivon, Adagene; Almac; Aduro; Amphista; Artios; Astex; AstraZeneca; Athena; Atrin; Avenzo; Avoro; Axiom; Baptist Health Systems; Bayer; BeiGene; BioCity Pharma; Blueprint; Boxer Other, Consulting/Advisory Role. Bristol Myers Squibb; C4 Therapeutics; Calithera; Cancer Research UK; Carrick Therapeutics; Circle Pharma; Clovis; Cybrexa; Daiichi Sankyo; Dark Blue Therapeutics; Diffusion; Duke Street Bio Other, Consulting/Advisory Role. 858 Therapeutics; EcoR1 Capital; Ellipses Pharma; EMD Serono; Entos; F-Star; Genesis Therapeutics; Genmab; Glenmark; GLG; Globe Life Sciences; GSK; Guidepoint; Ideaya Biosciences; Idience; Ignyta Other, Consulting/Advisory Role. I-Mab; ImmuneSensor; Impact Therapeutics; Institut Gustave Roussy; Intellisphere; Jansen; Kyn; MEI pharma; Mereo; Merck; Merit; Monte Rosa Therapeutics; Natera; Nested Therapeutics; Nexys; Nimbus Other, Consulting/Advisory Role. Novocure; Odyssey; OHSU; OncoSec; Ono Pharma; Onxeo; PanAngium Therapeutics; Pegascy; PER; Pfizer; Piper-Sandler; Pliant Therapeutics; Prolynx; Radiopharma Theranostics; Repare; resTORbio; Roche Other, Consulting/Advisory Role. Ryvu Therapeutics; SAKK; Sanofi; Schrodinger; Servier; Synnovation; Synthis Therapeutics; Tango; TCG Crossover; TD2; Terremoto Biosciences; Tessellate Bio; Theragnostics; Terns Pharmaceuticals Other, Consulting/Advisory Role. Tolremo; Tome; Thryv Therapeutics; Trevarx Biomedical; Varian; Veeva; Versant; Vibliome; Voronoi Inc; Xinthera; Zai Labs; ZielBio Other, Consulting/Advisory Role. Acrivon; Artios; AstraZeneca; Bayer; BeiGene; BioNTech; Blueprint; Bristol Myers Squibb; Boundless Bio; Clovis; Constellation; Cyteir; Eli Lilly; EMD Serono; Forbius; F-Star; GlaxoSmithKline ). Genentech; Haihe; Ideaya; ImmuneSensor; Insilico Medicine; Ionis; Ipsen; Jounce; Karyopharm; KSQ; Kyowa; Merck; Mirati; Novartis; Pfizer; Ribon Therapeutics; Regeneron; Repare; Rubius ). Rubius; Sanofi; Scholar Rock; Seattle Genetics; Tango; Tesaro; Vivace; Zenith ). J. Zhang, None. Y. Xu, Impact Therapeutics Employment, g., Board of Directors, non-salaried role). S. Chaudry, None.. K. H. Eng, None.. Y. Zhang, None.. V. J. Chen, None. G. Falchook, HealthONE; Sarah Cannon Research Institute Employment. Clinical Care Options Other, Honoraria. Abbvie; BostonGene; BostonGene; BridgeBio Pharma; EMD Serono; Fujifilm; Inspirna; Jubilant Pharmaceuticals; Merck; Navire; Predicine Other, Consulting/Advisory Role. Regeneron; Sanofi; Silicon Therapeutics; Silicon Therapeutics; Teon Therapeutics; Turning Point Therapeutics Other, Consulting/Advisory Role. Total Health Conferencing Other, Speakers’ Bureau. 3-V Biosciences; Abbisko; Abbvie; ABL Bio; Accutar Biotech; ADC Therapeutics; Agenus; Aileron Therapeutics; American Society of Clinical Oncology; Amgen; ARMO BioSciences; Artios; AstraZeneca; Bayer ). BeiGene; Bicycle Therapeutics; Bioatla; BioInvent; Biomea Fusion; Biothera; Black Diamond Therapeutics; Boehringer Ingelheim; Celgene; Celldex; Centessa Pharmaceuticals; Ciclomed ). Conjupro Biotherapeutics; Curegenix; Curis; Cyteir; Daiichi; DelMar Pharmaceuticals; eFFECTOR Therapeutics; Eikon Therapeutics; EMD Serono; Epizyme; Erasca; Exelixis; Freenome; Fujifilm; Genmab ). GlaxoSmithKline; Harbour BioMed; Hutchison MediPharma; IDEAYA Biosciences; IgM Biosciences; Ignyta; Immunitas; Immunogen/MacroGenics; Incyte; Jacobio; Jazz Pharmaceuticals; Jounce Therapeutics ). Jubilant Pharmaceuticals; Kineta; Kolltan Pharmaceuticals; Kura Oncology; Lilly; Loxo; MD Anderson Cancer Center; MedImmune; Merck; Metabomed; Millennium; Mirati Therapeutics; miRNA Therapeutics ). Molecular Templates;Navire; NGM Biopharmaceuticals; NiKang Therapeutics; Novartis; Nuvectis Pharma; OncoMed; Oncorus; Oncothyreon; Phanes Therapeutics; Poseida; Precision Oncology ). Prelude Therapeutics; PureTech; Pyramid Biosciences; Pyxis; RasCal; Regeneron; Relay Therapeutics; Rgenix; Ribon Therapeutics; Roche; Samumed; Sapience Therapeutics; Sarah Cannon Research Institute ). Seagen; Silicon Therapeutics; Simcha Therapeutics; Sirnaomics; Strategia Therapeutics; Syndax; Synthorx; Taiho Pharmaceutical; Takeda; Tallac Therapeutics; Tango Therapeutics; Tarus Therapeutics ). Tarveda Therapeutics; TeneoBio; Tesaro; Tocagen; Turning Point Therapeutics; Vegenics; Xencor; Zhuhai Yufan Biotechnologies ). Handbook of Targeted Cancer Therapy Patent, Other Intellectual Property, Other, Royalties. Amgen; Bristol-Myers Squibb; EMD Serono; Fujifilm; Millennium; Sarah Cannon Research Institute; Synthorx/Sanofi Travel, Other, Accommodations, Expenses.
Cited in
Control: 9865 · Presentation Id: 12217 · Meeting 21436