Preliminary results from the phase 1b/2, open-label, multi-center study of ZL-1310, a DLL3-targeted ADC, in patients with neuroendocrine carcinomas and other selected solid tumors
Presenter: Rohit Thummalapalli, MD Session: Phase I Clinical Trials Time: 4/21/2026 9:00:00 AM → 4/21/2026 12:00:00 PM
Authors
Rohit Thummalapalli 1 , Ming Lu 2 , Alexander Spira 3 , Amr Mohamed 4 , Rahul Aggarwal 5 , Yu Wang 6 , Namrata Vijayvergia 7 , Jordi Rodon 8 , Andrew Scott Paulson 9 , Pingkuan Zhang 10 , Hui Yang 11 , Yuan Xin 11 , Jingmin Wen 11 , Jie Chen 12 1 Memorial Sloan Kettering Cancer Center, New York, NY, 2 Digestive Oncology Department, Peking University Cancer Hospital and Institute; Digestive Oncology Department, Beijing GoBroad Hospital, Beijing, China, 3 Virginia Cancer Specialists, Fairfax, VA, 4 Department of Medicine, Division of Hematology and Medical Oncology, UH Seidman Cancer Center. Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, 5 University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, 6 Interventional Oncology Department, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China, 7 Fox Chase Cancer Center, Philadelphia, PA, 8 MD Anderson Cancer Center, Houston, TX, 9 Texas Oncology, Dallas, TX, 10 Zai Lab (US) LLC, Cambridge, MA, 11 Zai Lab (Shanghai) Co., Ltd, Shanghai, China, 12 Neuroendocrine Oncology Department, Fudan University Shanghai Cancer Center, Shanghai, China
Abstract
Background: Patients with neuroendocrine carcinomas (NECs) have limited treatment options after front-line therapy, and have a high unmet clinical need for new effective therapies. Delta-like ligand 3 (DLL3) is broadly expressed in NECs. ZL-1310 is a novel antibody-drug conjugate (ADC) that employs the TMALIN ® ( T umor M icroenvironment A ctivable LIN ker-payload) platform, an anti-DLL3 monoclonal antibody linked to a topoisomerase I inhibitor payload via a stable protease-cleavable linker. We report initial safety and efficacy data from Phase 1b of the ZL-1310-002 (NCT06885281) trial assessing ZL-1310 monotherapy in patients (pts) with NECs. Methods: Patients had advanced/metastatic de novo NECs (excluding small cell lung cancer) and had progressed on or after platinum-based chemotherapy. ZL-1310 was given via IV at a starting dose of 1.6 mg/kg every 3 weeks until disease progression or unacceptable toxicity. Antitumor activity was assessed by RECIST v1.1 (investigator-assessed). Results: As of 11 Nov 2025, 28 pts with NECs were treated (GastroEnteroPancreatic (GEP)-NEC: 50%, cervical/uterine: 14%, unknown primary 14%, neuroendocrine prostate carcinoma (NEPC) 7%, bladder 7%, large cell neuroendocrine carcinoma of the lung (LCNEC-L) 4%, mediastinal 4%); median age was 53 years (range: 27, 76), ECOG PS: 0/1 (32%/68%); male: 18 (64%); Asian: 64%; 5 (18%) of the pts had 2 lines of prior therapy. DLL3 expression by immunohistochemistry was performed retrospectively in central laboratory and was available for 26 pts and 80% (21/26) patients were positive (cutoff: H-score ≥ 1). The median H-score was 123 (range: 0-288). Median follow-up was 2.9 months (range: 0.2-6.0); pts received a median of 3.2 treatment cycles (range: 1, 9). Seventeen (61%) of pts remain on treatment; disease progression was the most common reason for treatment discontinuation. A total of 25 pts (89%) had treatment-emergent adverse events (TEAEs), and 4 (14.3%) had Grade 3+ TEAEs. Most common TEAEs (>20%, all grade) include anemia (39%), nausea (36%) and vomiting (29%). One pt (3.6%) decreased the dose of ZL-1310 due to AE (G3 neutrophil count decreased); one pt (3.6%) experienced G2 interstitial lung disease leading to treatment discontinuation. No Grade 5 AE was reported. Objective response rate (ORR) was 48% with 8 confirmed and 2 unconfirmed responses in 21 evaluable pts, including one pt with prior DLL3-targeted bispecific antibody treatment who achieved confirmed PR. Conclusions: ZL-1310 dosed at 1.6mg/kg Q3W is well tolerated. The AE profile observed in pts with NEC is generally consistent with that of SCLC from a larger study. The preliminary efficacy results are encouraging in this patient population with a high unmet need following platinum-based chemotherapy. Phase 2 expansion in NEC is ongoing to further evaluate the safety and efficacy of ZL-1310 and updated data will be presented.
Disclosure
R. Thummalapalli, Boehringer Ingelheim Other, Consulting or Advisory Role. Zai Lab ). M. Lu, None. A. Spira, NEXT Oncology Virginia Other, Leadership. CytomX Therapeutics Other, Honoraria. AstraZeneca/MedImmune Other, Honoraria. Merck Other, Honoraria. Takeda Other, Honoraria. Amgen Other, Honoraria. Janssen Oncology Other, Honoraria. Novartis Other, Honoraria. Incyte Other, Consulting or Advisory Role. Amgen Other, Consulting or Advisory Role. Novartis Other, Consulting or Advisory Role. Mirati Therapeutics Other, Consulting or Advisory Role. Gritstone Oncology Other, Consulting or Advisory Role. Jazz Pharmaceuticals Other, Consulting or Advisory Role. Takeda Other, Consulting or Advisory Role. LAM Therapeutics ). Roche ). AstraZeneca ). Boehringer Ingelheim ). Astellas Pharma ). A. Mohamed, None.. R. Aggarwal, None.. Y. Wang, None.. N. Vijayvergia, None.. J. Rodon, None.. A. Paulson, None. P. Zhang, Zai Lab Employment, Stock. H. Yang, Zai Lab Employment, Stock. Y. Xin, Zai Lab Employment, Stock. J. Wen, Zai Lab Employment, Stock. J. Chen, None.
Cited in
Control: 10380 · Presentation Id: 12095 · Meeting 21436