692P - First-in-human study of ELU001, a targeted nanoparticle drug conjugate, in subjects with folate receptor α (FRα) overexpressing solid tumors

Background

ELU001 is small nanoparticle drug conjugate (∼6 nm), designed to penetrate deep into solid tumors and be eliminated rapidly by the kidneys to reduce toxicity versus antibody drug conjugates. ELU001 has ∼13 folic acid targeting moieties and ∼21 cathepsin-B cleavable exatecans, a topoisomerase-1 inhibitor, covalently bound to short polyethylene glycol chains surrounding a silica core. ELU001 binds cancer cells expressing FRα releasing exatecan intracellularly. ELU001 demonstrated efficacy in preclinical models with low to high levels of FRα.

Methods

Phase 1 / 2 multicenter, open label clinical trial. Part 1, Dose Escalation, enrolled patients with cancers likely to overexpress FRα. Escalating doses of ELU001, administered once a week (QW) (0.58-1.94 mg/m² for 3 weeks, 1 week rest), every other week (Q2W) (1.5-2.25 mg/m²), or every three weeks (Q3W) (2.75-3.5 mg/m²). Primary objective of Part 1: identify the starting dose and regimen for Part 2, Tumor Group Expansion.

Results

As of May 8, 2023, 40 patients (18 ovarian, 7 endometrial, 10 colorectal, 3 non-small cell lung and 2 cholangiocarcinoma) enrolled in Part 1 (15 QW, 14 Q2W, 11 Q3W), median prior lines of therapy 5 (2-13). To date 23 were evaluable for first tumor assessment at ∼8 weeks after first dose (1 Partial Response,18 Stable Disease and 4 Progressive Disease). 7 patients continued treatment for >6 cycles (4 for >8, 3 for >11). Treatment-Emergent Adverse Events: Grade 3 and 4 (≥ 10%): QW/Q2W/Q3W: neutropenia (46.7%/28.6%/50%), anemia (46.7%/28.6%/30%), leukopenia (40.0%/14.3%/10.0%), and thrombocytopenia (20%/7%/40%). Grade 1 and 2, (All regimens ≥ 20%): anemia (38.5%), fatigue (23.1%), neutropenia (30.8%), diarrhea (20.5%) and vomiting (23.1%). No evidence of ocular, liver, renal or cardiac toxicities, interstitial lung disease or peripheral neuropathy. Preliminary half-life ∼22 hours. The Q2W regimen had a better hematological safety profile with no related discontinuations.

Conclusions

Safety and efficacy of ELU001 demonstrated expected, manageable safety profile based on the payload, exatecan, with promising activity in heavily pretreated patients across several cancer indications with low, moderate or high FRα expression.

Clinical trial identification

NCT05001282.

Editorial acknowledgement

Legal entity responsible for the study

Elucida Oncology.

Funding

Elucida Oncology.

Disclosure

W.W. Ma: Financial Interests, Institutional, Principal Investigator: Elucida Oncology. D. Orr, G.P. Adams, A.W. Tolcher: Financial Interests, Institutional, Local PI: Elucida Oncology. C.A. Perez: Financial Interests, Institutional, Local PI: Accutar Biotech, Kinnate Biopharma, Relay Therapeutics, Seagen Inc., Kura Oncology, Hyamab Inc., Xilio Therapeutics, Elucida Oncology, Tallac Therapeutics, Ribbon Therapeutics, Mirati Therpeutics, Elpiscience Biopharmaceuticals, Dracen Pharmaceuticals, Zhuhai Yufan Biotechnologies Co., Genentech, Inc., Jazz Pharmaceuticals, Artios Pharma. Y.R. Murciano-Goroff: Financial Interests, Institutional, Local PI: Elucida Oncology. E.P. Hamilton: Financial Interests, Institutional, Other, Consulting/Advisory Role: Genentech/Roche, Novartis, Lilly, Pfizer, Mersana, iTeos, Janssen, Loxo, Relay Therapeutics, Olema Pharmaceuticals, Orum Therapeutics, Stemline Therapeutics, Arcus, AstraZeneca, Daiichi Sankyo, Seagen, Ellipses Pharma, Greenwich LifeSciences, Tubulis, Verascity Science, Theratechnologies; Financial Interests, Institutional, Research Grant: Oncomed, Genentech/Roche, Zymeworks, Rgenix, Arqule, Clovis, Millennium, Acerta Pharma, Sermonix Pharmaceuticals, Black Diamond, Karyopharm, Curis, Syndax, Novartis, Boehringer Ingelheim, Immunomedics, FujiFilm, Taiho, Deciphera, Molecular Templates, Onconova Therapeutics, Dana Farber Cancer Hospital, Hutchinson MediPharma, MedImmune, Seagen, Compugen, TapImmune, Lilly, Pfizer, H3 Biomedicine, Merus, Regeneron, Arvinas, StemCentRx, Verastem, eFFECTOR Therapeutics, CytomX, InventisBio, Lycera, Mersana, Radius Health, AbbVie, Nucana, Leap Therapeutics, Zenith Epigenetics, Harpoon, Orinove, AstraZeneca, Tesaro, Macrogenics, EMD Serono, Daiichi Sankyo, Syros, Sutro, G1 Therapeutics, PharmaMar, Olema, Immunogen, Plexxicon, Amgen, Akesobio Australia, Shattuck Labs, ADC Therapeutics, Aravive, Atlas MedX, Ellipses, Incyte, Jacobio, Mabspace Biosciences, ORIC Pharmaceuticals, Pieris Pharmaceuticals, Pionyr Immunotherapeutics, Repertoire Immune Medicine, Treadwell Therapeutics, Accutar Biotechnology, Cascadian Therapeutics, Artios, BeiGene, Bliss BioPharmaceuticals, Context Therapeutics, Cullinan-Florentine, Dantari, Duality Biologics, Elucida Oncology, Infinity Pharmaceuticals, K-Group Beta, Kind Pharmaceuticals, Loxo Oncology, Oncothyreon, Orum Therapeutics, Prelude Therapeutics, Profound Bio, Relay Therapeutics, Tolmar, Torque Therapeutics. Y. Zhao: Financial Interests, Institutional, Local PI: Elucida Oncology, PDS Biotechnology, Zai Lab, Mirati, Alpine, Pfizer, Merck. C. Anders: Financial Interests, Institutional, Local PI: Elucida Oncology; Financial Interests, Institutional, Research Funding: PUMA, Lilly, Merck, Seattle Genetics, Nektar, Tesaro, G1-Therapeutics, ZION, Novartis, Pfizer, AstraZeneca, Immunomedics, Athenex, Caris, Roche; Financial Interests, Personal, Research Funding: Novartis; Financial Interests, Personal, Advisory Role: Genentech, Eisai, Seattle Genetics, AstraZeneca, Novartis, Immunomedics, Ipsen, Athenex, Roche; Financial Interests, Personal, Other, Honoraria: Genentech, Eisai, Ipsen, Seattle Genetics, AstraZeneca, Novartis, Immunomedics, Elucida Oncology, Athenex; Financial Interests, Personal, Royalties: UpToDate, Jones and Bartlet. C. Reddick, H. Wroe McClintock, E. Bayever: Financial Interests, Personal, Full or part-time Employment: Elucida Oncology.