Introduction/Background DB-1303 is an antibody-drug conjugate (ADC) consisting of a humanized anti-HER2 IgG1 monoclonal antibody, covalently linked to a proprietary DNA topoisomerase I inhibitor (P1003) via a maleimide tetrapeptide-based cleavable linker.

Methodology This is a multicentre, dose-escalation/expansion study evaluating DB-1303 IV Q3W in previously treated patients with solid tumours and compelling antitumor activity has been observed (ASCO 2023). This is the first report of dose escalation and expansion results of DB-1303 in patients with HER2-expressing (IHC 1/2/3+ or ISH+) advanced/metastatic endometrial cancer (EC).

Results As of May 8, 2023, 32 patients with EC had received 7 or 8 mg/kg doses of DB-1303. The most common histological sub-type was uterine serous papillary carcinoma (USPC, 34.4%), adenocarcinoma (25.0%), and uterine carcinosarcoma (UCS, 18.8%). The median treatment duration was 2.6 (range, 0.7–10.4) months with 29 patients (90.6%) remaining on treatment. Median number of prior regimens for metastatic disease was 2 (range, 1–10). Nineteen patients (59.4%) had prior immunotherapy (IO) therapy. A total of 17 patients were evaluable for response. Ten patients (58.8%) had objective partial tumour response (4 confirmed, and 6 requiring further confirmation) per RECIST 1.1: 7 USPC (87.5%, 7/8), 1 UCS (50.0%, 1/2), 1 mixed adenocarcinoma (50.0%, 1/2), and 1 adenocarcinoma (33.3%, 1/3). The ORRs for patients at 7 and 8 mg/kg dose were 50.0% (2/4) and 61.5% (8/13), respectively. The overall DCR was 94.1%. Treatment-emergent adverse events (TEAEs) of any grade occurred in 30 patients (93.8%), and the most common (≥20%) were nausea (50.0%), fatigue (31.2%), and vomiting (28.1%); of ≥grade 3 occurred in 10 patients (31.2%), and the most common (≥5%) were hypokalaemia (12.5%), anaemia (6.2%), and syncope (6.2%). No TEAEs led to drug discontinuation or death. No interstitial lung disease occurred.

Conclusion DB-1303 demonstrated a manageable safety profile and promising antitumor activity, with high disease control in patients with advanced/metastatic EC.

Disclosures Kathleen Moore: Receipt of grants/research supports: PTC Therapeutics, Lilly, Merck, Genentech, Clovis, Verastem, GSK; Receipt of honoraria or consultation fees: Aadi, Astra Zeneca, Aravive, Alkemeres, Blueprint pharma, Clovis, Caris, Duality, Eisai, GSK, Genentech/Roche, Hengrui, Immunogen, IMab, Merck, Mersana, Myriad, OncXerna, OncoNova, Panavance, VBL Therapeutics, Verastem; Other support: Associate Director GOG Parnters, GOG Foundation BOD.

Vicky Makker: Receipt of grants/research supports: AstraZeneca (Inst), Bristol Myers Squibb (Inst), Clovis Oncology (Inst), Duality (Inst), Eisai (Inst), Faeth Therapeutics (Inst), Karyopharm Therapeutics (Inst), Lilly (Inst), MSD (Inst), Takeda (Inst), Zymeworks (Inst); Receipt of honoraria or consultation fees: Merck and Eisai-TRAVEL; Other support: Unpaid consulting or advisory role: AarQule, AstraZeneca, Clovis Oncology, Duality, Eisai, Faeth Therapeutics, GlaxoSmithKline, IBM, Immunocore, ITeos Therapeutics, Kartos Therapeutics, Karyopharm Therapeutics, Lilly, MSD, Moero, Morphosys, Novartis, Takeda, Zymeworks

Oladapo Yeku: Receipt of grants/research supports: Ascendis Pharma A/S, Avenge Bio, Inc., Immunocore Limited, Duality Biologics, Merck Sharp & Dohme Corporation, Pionyr Immunotherapeutics Inc., ProfoundBio, and the Department of Defense; Receipt of honoraria or consultation fees: Celldex Therapeutics, GIMV NV, TigaTx Inc. Advisory board role at hC Bioscience.

Bhavana Pothuri: Receipt of grants/research supports: Tesaro/GSK, Merck, AstraZeneca, Karyopharm, Sutro, Immunogen, VBL Therapeutics, Onconova,clovis, Genentech, Mersana, Ceslion, Takada, Incyte, Toray, Seagen; Receipt of honoraria or consultation fees: Tesaro/GSK, Merck, AstraZeneca, Eli Lilu, Sutro, SeaGen, Eisai, Natera, GOG Partners.

Whitfield Growden: Receipt of honoraria or consultation fees: Duality Biologics/Advisory Board member.

Erika Hamilton: Receipt of grants/research supports: Abbvie (Inst); Accutar Biotech (Inst); Acerta Pharma (Inst); ADC Therapeutics (Inst); Akeso Biopharma (Inst); Amgen (Inst); Aravive (Inst); ArQule (Inst); Artios (Inst); Arvinas (Inst); AstraZeneca (Inst); AtlasMedx (Inst); BeiGene (Inst); Black Diamond Therapeutics (Inst); Bliss Biopharmaceutical (Inst); Boehringer Ingelheim (Inst); Cascadian Therapeutics (Inst); Clovis Oncology (Inst); Compugen (Inst); Context Therapeutics (Inst); Cullinan Oncology (Inst); Curis (Inst); CytomX Therapeutics (Inst); Daiichi Sankyo (Inst); Dana Farber Cancer Hospital (Inst); Dantari (Inst); Deciphera (Inst); Duality Biologics (Inst); eFFECTOR Therapeutics (Inst); Ellipses Pharma (Inst); Elucida Oncology (Inst); EMD Serono (Inst); Fujifilm (Inst); G1 Therapeutics (Inst); Genentech/Roche (Inst); H3 Biomedicine (Inst); Harpoon (Inst); Hutchison MediPharma (Inst); Immunogen (Inst); Immunomedics (Inst); Incyte (Inst); Infinity Pharmaceuticals (Inst); InventisBio (Inst); Jacobio (Inst); K-Group Beta (Inst); Karyopharm Therapeutics (Inst); Kind Pharmaceuticals (Inst); Leap Therapeutics (Inst); Lilly (Inst); Loxo (Inst); Lycera (Inst); MabSpace Biosciences (Inst); Macrogenics (Inst); MedImmune (Inst); Mersana (Inst); Merus (Inst); Millennium (Inst); Molecular Templates (Inst); Novartis (Inst); Nucana (Inst); Olema Pharmaceuticals (Inst); OncoMed (Inst); Onconova Therapeutics (Inst); Oncothyreon (Inst); ORIC Pharmaceuticals (Inst); Orinove (Inst); Orum Therapeutics (Inst); Pfizer (Inst); PharmaMar (Inst); Pieris Pharmaceuticals (Inst); Pionyr (Inst); Plexxikon (Inst); Prelude Therapeutics (Inst); ProfoundBio (Inst); Radius Health (Inst); Regeneron (Inst); Relay Therapeutics (Inst); Repertoire Immune Medicines (Inst); Rgenix (Inst); Seagen (Inst); Sermonix Pharmaceuticals (Inst); Shattuck Labs (Inst); Stem CentRx (Inst); Sutro Biopharma (Inst); Syndax (Inst); Syros Pharmaceuticals (Inst); Taiho Pharmaceutical (Inst); TapImmune Inc. (Inst); Tesaro (Inst); Tolmar (Inst); Torque (Inst); Treadwell Therapeutics (Inst); Verastem (Inst); Zenith Epigenetics (Inst); Zymeworks (Inst); Other support: Consulting or Advisory Role: AstraZeneca (Inst); Daiichi Sankyo (Inst); Ellipses Pharma (Inst); Genentech/Roche (Inst); Greenwich LifeSciences (Inst); ITeos Therapeutics (Inst); Janssen (Inst); Lilly (Inst); Loxo (Inst); Mersana (Inst); Novartis (Inst); Olema Pharmaceuticals (Inst); Orum Therapeutics (Inst); Pfizer (Inst); Relay Therapeutics (Inst); Seagen (Inst); Stemline Therapeutics (Inst); Theratechnologies (Inst); Tubulis GmbH (Inst); Verascity Science (Inst)