Intracranial activity of ZL-1310, a DLL3-targeted ADC, in patients with previously treated extensive-stage small cell lung cancer and baseline brain metastasis: Analysis of a phase 1 trial
Presenter: Pingkuan Zhang, MD Session: Phase I Clinical Trials Time: 4/21/2026 9:00:00 AM → 4/21/2026 12:00:00 PM
Authors
Pedro Rocha 1 , Manish Patel 2 , Yi-Long Wu 3 , Jun Zhao 4 , Grace Dy 5 , María Eugenia Olmedo García 6 , Qiming Wang 7 , Valentina Gambardella 8 , Oscar Juan-Vidal 9 , Afshin Dowlati 10 , David Vicente Baz 11 , Alexander Spira 12 , Anne C. Chiang 13 , Yingying Du 14 , Martin Gutierrez 15 , Xiaorong Dong 16 , Jie Hu 17 , Mariam Alexander 18 , Haiyong Wang 19 , Wenxiu Yao 20 , Liza Villaruz 21 , Zhen Wang 3 , Pingkuan Zhang 22 , Renke Zhou 22 , Xiao Wang 22 , Luis Paz-Ares 23 1 Instituto de Investigacion Oncologica Vall d’Hebron (VHIO), Barcelona, Spain, 2 Florida Cancer Specialists/Sarah Cannon Research Institute, Sarasota, FL, 3 Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China, 4 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China, 5 Roswell Park Comprehensive Cancer Center, Buffalo, NY, 6 Hospital Universitario Ramón y Cajal, Madrid, Spain, 7 Henan Cancer Hospital, Zhengzhou, China, 8 Hospital Clínico Universitario de Valencia, INCLIVA, Valencia, Spain, 9 Hospital Universitari i Politècnic La Fe, Valencia, Spain, 10 University Hospitals Seidman Cancer Center and Case Western Reserve University, Cleveland, OH, 11 Hospital Universitario Virgen Macarena, Sevilla, Spain, 12 NEXT Oncology Virginia, Fairfax, VA, 13 Yale Cancer Center, Yale School of Medicine, New Haven, CT, 14 The First Affiliated Hospital of Anhui Medical University, Hefei, China, 15 Hackensack University Medical Center, Hackensack, NJ, 16 Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, 17 Zhongshan Hospital, Fudan University, Shanghai, China, 18 Medical University of South Carolina, Charleston, SC, 19 Cancer Hospital of Shandong First Medical University, Jinan, China, 20 Sichuan Cancer Hospital, Chengdu, China, 21 UPMC Hillman Cancer Center, Pittsburgh, PA, 22 Zai Lab (US) LLC, Cambridge, MA, 23 Hospital Universitario 12 de Octubre, Madrid, Spain
Abstract
Background: Brain metastasis (BM) is prevalent in extensive-stage small-cell lung cancer (ES-SCLC) and also a common cause for treatment failure. BM remains as an unmet need with limited treatment options available such as palliative radiotherapy. 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 protease-cleavable linker. ZL-1310 has demonstrated encouraging systemic efficacy in heavily pre-treated ES-SCLC. We report the initial intracranial efficacy of ZL-1310 from a phase 1 study. Methods: This multi-country Phase 1 study (NCT06179069) enrolled adults with ES-SCLC who have progressed following ≥1 platinum-based chemotherapy. Those with stable or asymptomatic BM are eligible (including those with no prior brain radiotherapy). ZL-1310 is given intravenously every 3 weeks until disease progression or unacceptable toxicity. Systemic efficacy was assessed by investigators using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Intracranial efficacy was assessed by blinded independent radiologists using Modified Criteria for Radiographic Response Assessment in NeuroOncology (mRANO). Results: As of 1 Aug 2025, 104 pts received ZL-1310 across 6 dose levels (0.8-2.8 mg/kg). The median age was 65 years (range: 36, 80); 42.3% of pts were female, and 28.8% were Asian. Fifty-four (51.9%) had 1 prior line and the remaining 50 (48.1%) had 2 or more lines of prior therapies. A total of 94 (90.4%) received a prior anti-PD‑L1, 13 (12.5%) had prior lurbinectedin, and 10 (9.6%) had prior DLL3-targeted therapy. Brain metastases were present in 33 (31.7%) pts (including 11 pts with untreated BM) at baseline. Independently reviewed intracranial efficacy results were available for 24 pts, including 15 pretreated with radiation and 9 untreated. Confirmed intracranial response was 58.3% (14/24, 95% CI: 36.6, 77.9%), including 5 CR and 9 PR. The intracranial response rate in pts without prior brain radiation was 66.7% (6/9) and 53.3% (8/15) in pts with prior brain radiation. Intracranial disease control rate was 95.8% (23/24). The median time to onset of intracranial response was 5.6 weeks (min 5.1, max 8.7 weeks). Of the 33 pts with BM and systemic efficacy evaluable, confirmed ORR was 61%, including 1 confirmed CR. Grade ≥3 treatment-related adverse events were reported for 22/104 (21.2%) pts overall and 5/39 (12.8%) pts in the 1.6 mg/kg dose level; those reported in ≥2 pts at the 1.6 mg/kg dose level included anemia and neutropenia (2 pts each). Independent mRANO evaluation is ongoing and updated data will be provided. Conclusions: ZL-1310 is well tolerated and demonstrated encouraging systemic efficacy in heavily pretreated ES-SCLC with BM. The preliminary independent assessment also showed ZL-1310 has high intracranial efficacy including in patients with untreated BM.
Disclosure
P. Rocha, Amgen Other, Honoraria. Daiichi Sankyo Other, Consulting or advisory role. IGES Pharma Consulting or advisory role. AstraZeneca Travel. Bristol Myers Squibb Travel. Daiichi Sankyo Travel. Kyowa Kirin Travel. MSD Travel. PharmaMar Travel. Roche Travel. M. Patel, ION Pharma Other Business Ownership. Daiichi Sankyo Other, Consulting or Advisory Role. UCB Japan Other, Consulting or Advisory Role. Kura Oncology Other, Consulting or Advisory Role. Accutar Biotech Other, Consulting or Advisory Role. Mitsubishi Tanabe Pharma Other, Consulting or Advisory Role. Shivanka Research Other, Consulting or Advisory Role. Johnson & Johnson/Janssen Consulting or Advisory Role. Agenus ). Boehringer Ingelheim ). Cyteir Therapeutics ). Daiichi Sankyo ). Genentech/Roche ). Janssen ). Loxo ). Macrogenics ). Merck ). Moderna Therapeutics ). Pfizer ). Prelude Therapeutics ). Y. Wu, None.. J. Zhao, None. G. Dy, Amgen Other, Consulting fee and/or Honoraria. AstraZeneca Consulting fee and/or Honoraria. Bayer Consulting fee and/or Honoraria. Bristol Myers Squibb Consulting fee and/or Honoraria. Janssen Consulting fee and/or Honoraria. Novartis Consulting fee and/or Honoraria. Regeneron Consulting fee and/or Honoraria. Whitehawk Therapeutics Consulting fee and/or Honoraria. M. Olmedo García, None.. Q. Wang, None.. V. Gambardella, None.. O. Juan-Vidal, None.. A. Dowlati, None.. D. Vicente Baz, 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. Bristol Myers Squibb Other, Honoraria. Bayer Other, Honoraria. Prelude Therapeutics Other, Honoraria. Abbvie Other, Honoraria. Astellas Pharma 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. A. C. Chiang, Amgen Other, Advisory board/consulting. Abbvie Other, Advisory board/consulting. AstraZeneca Other, Advisory board/consulting. BI Other, Advisory board/consulting. Daichi Other, Advisory board/consulting. Fosun Other, Advisory board/consulting. Genentech Other, Advisory board/consulting. Janssen Other, Advisory board/consulting. Merck Other, Advisory board/consulting. Zai Lab Other, Advisory board/consulting. Amgen ). AbbVie ). AstraZeneca ). Genentech ). BMS ). Zai Lab ). Jazz ). AstraZeneca Other, Member of the data and safety monitoring board. . Y. Du, None. M. Gutierrez, Merck Other, Advisory Board/Consultant. Incyte Biosciences Other, Advisory Board/Consultant. Outcomes Matter Innovations LLC Stock. Genomic Testing Cooperative Stock. COTA Stock. Lisata Therapeutics Inc. ). Georgetown University ). Constellation Pharmaceuticals Inc. ). Bristol Meyers Squibb ). AstraZeneca ). Incyte Corporation ). Memorial Sloan Kettering Cancer Center ). Prelude Therapeutics Inc ). Zai Lab ). Boehringer Ingelheim ). Johns & Johnson ). BeiGene ). Novartis ). Merck & Co. ). Seagen Inc. ). X. Dong, None.. J. Hu, None. M. Alexander, Abbvie Other, Consultant or Advisory Board. Amgen Other, Consultant or Advisory Board. Daiichi Sankyo Other, Consultant or Advisory Board. Janssen Other, Consultant or Advisory Board. Regeneron Other, Consultant or Advisory Board. CHEST Other, Consultant or Advisory Board. IDEOlogy Health Other, Speaker Honoraria. MedStar Other, Speaker Honoraria. H. Wang, None.. W. Yao, None.. L. Villaruz, None.. Z. Wang, None. P. Zhang, Zai Lab Employment, Stock. R. Zhou, Zai Lab Employment, Stock. X. Wang, Zai Lab Employment, Stock. L. Paz-Ares, Zai Lab Employment, Stock.
Cited in
Control: 10362 · Presentation Id: 12099 · Meeting 21436