A phase 1/2 study of a first-in-human immune-stimulating antibody conjugate (ISAC) BDC-1001 in patients with advanced HER2-expressing solid tumors.

• DOI: 10.1200/jco.2023.41.16_suppl.2538
• Publication Date: 2023-06-04T15:12:10Z
• Authors: Bob T. Li; Mark D. Pegram; Keun-Wook Lee; Manish Sharma; Jeeyun Lee; Alexander I. Spira; Glenn J. Hanna; Yoon-Koo Kang; Drew W. Rasco; Kathleen N. Moore; Benjamin Adam Wei...; Michael N. Alonso; Jason Ptacek; Ming Yin; Coya Tapia; Lu Xu; Edith A. Perez; Ecaterina Elena D...
• Keywords: 03 medical and health sciences; 0302 clinical medicine; 3. Good health

2538 Background: BDC-1001 is a HER2-targeted immune-stimulating antibody conjugate (ISAC), designed to trigger local activation of the innate immune system and generate durable tumor-targeted adaptive response. incorporates trastuzumab biosimilar (EG12014) conjugated proprietary TLR7/8 agonist using non-cleavable linker cell membrane-impermeable payload. An international phase 1/2 study was initiated evaluate safety ± nivolumab (nivo) identify recommended 2 dose (RP2D) considering PK/PD analyses preliminary efficacy. Methods: Dose-escalation (3+3, +backfills) enrolled patients (pts) with HER2-positive (amplified, or IHC 3+) HER2 low (IHC 2+ not amplified) solid tumors who had progressed after standard therapies. given IV q3w, q2w, q1w as monotherapy (mono; n=91) q2w nivo 240 mg (combo; n=27). Results: As Nov 23, 2022, 118 pts 16 different tumor types, were doses ranging from 0.15 20 mg/kg. Mean age 61 yrs median 4 5 prior lines therapy (range, 1-11; 1-14; anti-HER2 (HER2Tx) [66%/70%], immunotherapy (IO) [23%/22%]) for mono combo, respectively. Median follow-up time 5.0-6.1 months. Treatment well tolerated only 1 DLT (Gr3 supraventricular tachycardia) at 8 mg/kg combo cohort. Low-grade IRRs most common related TEAEs (mono, 26.5%; 25.9%). A SAE (Gr4, bronchopulmonary hemorrhage) seen in pt 1.1%). Antitumor activity observed range malignancies. There confirmed (RECIST 1.1) PRs (all MSS low/intermediate TMB, Tx: HER2Tx, IO) including colon cancer (CRC) q3w cohort, 3 cohorts (mono 1/7; 2/7; ovarian, biliary, rectal cancers). After data cut, an additional PR (unconfirmed) reported week 6 CRC receiving 12m/kg 1qw combo. Ten SD lasting ≥6 months (8 mono; combo; HER2Tx; IO; e.g., endometrial, colorectal, gastric). Durable SDs frequent cohorts. exposure (e.g., C min ) correlated among Increases myeloid T infiltration markers post-Tx biopsies align mechanism action (MoA). No anti-drug antibodies detected. Conclusions: well-tolerated. Targeted serum levels achieved, encouraging clinical noted heavily pretreated various positive tumors, especially Immune biomarker changes plasma consistent MoA this ISAC. These support further development expansion HER2-expressing RP2D. Clinical trial information: NCT04278144 .