Zai Lab Showcases 54% Brain Metastases Response for ZL-1310 ADC in SCLC at AACR Investor Call

Key Points

• Zai Lab’s ADC zocilurtatug pelitecan (ZL-1310, "zoci") showed a 54% intracranial overall response rate in SCLC patients with brain metastases (62% at the 1.6 mg/kg dose) with 17% complete responses, rapid onset of effect and a median time on response of nine months, while safety was manageable (primarily myelosuppression and GI symptoms) with no new intracranial safety signals reported.
• In extrapulmonary neuroendocrine carcinomas and other DLL3-expressing tumors, zoci produced a 38% ORR and ~56% disease control rate (33% in GEP-NEC, 44% in other EP-NECs), with responses observed regardless of DLL3 IHC status but possible reduced activity after prior irinotecan/topoisomerase‑1 exposure.
• Zai Lab is advancing zoci globally, with the Phase III DLLEVATE study ongoing (expected enrollment completion H1 2027 and potential accelerated approval in 2028), and multiple combination programs planned or underway with Amgen and Boehringer Ingelheim to evaluate PD‑L1, T‑cell engager, and chemotherapy triplet strategies in first‑line and later settings.

Zai Lab NASDAQ: ZLAB hosted an investor call tied to the 2026 American Association for Cancer Research (AACR) meeting to highlight new data for its DLL3-targeted antibody-drug conjugate (ADC) zocilurtatug pelitecan (zoci; ZL-1310) in small cell lung cancer (SCLC) with brain metastases and in extrapulmonary neuroendocrine carcinomas (EP-NEC). The call featured presentations from Dr. Luis Paz-Ares of Hospital Universitario 12 de Octubre and Dr. Rohit Thummalapalli of Memorial Sloan Kettering Cancer Center, followed by an update on development strategy from Dr. Rafael Amado, Zai Lab’s President and Head of Global Research and Development.

First-time intracranial activity data in extensive-stage SCLC

Paz-Ares described extensive-stage SCLC as “a high-grade, very aggressive carcinoma” with a propensity for brain metastases that can affect both survival and quality of life. He said about 20% of patients present with brain metastases at diagnosis and roughly 30% develop them over the course of disease. He noted real-world data suggesting median overall survival around eight months in patients with brain metastases, particularly those treated with whole-brain irradiation.

He presented first-time intracranial activity data for zoci from the dose escalation and expansion Phase 1 study ZL-1310, which is evaluating the ADC as monotherapy and in combination with atezolizumab, or atezolizumab plus carboplatin, in extensive-stage SCLC. The dataset had a February 2026 cutoff and a median follow-up of about eight months. Intracranial responses were assessed by an independent radiology committee using modified RANO brain metastasis criteria.

Among 136 patients in the study overall, 49 patients (36%) had brain metastases. About one-third of patients with brain metastases had not received prior brain irradiation before entering the trial, while roughly two-thirds had. Paz-Ares said more than 90% of the overall population had received PD-L1 therapy previously, and about 10% had received DLL3 inhibitors.

In patients with brain metastases who were response-evaluable, Paz-Ares reported an intracranial overall response rate (ORR) of 54%, including complete responses in 17% of cases. He also highlighted dose-related activity, stating response rates were highest at 1.6 mg/kg (62%) versus 1.2 mg/kg (50%). Responses were observed both in patients with prior radiotherapy (50%) and those without prior radiotherapy (60%). He added that 21 of 22 responders had responses by the first tumor assessment at about six weeks, and that 14 responses were ongoing with a median time on response of nine months.

On safety, Paz-Ares said the drug was “reasonably well tolerated,” with side effects consistent with topoisomerase-1 inhibitor mechanisms, including cytopenias (myelosuppression) as well as nausea, fatigue, and asthenia, mostly grade 1-2. At 1.6 mg/kg, he cited grade 3 or higher adverse events in the “range of 15%” and said no new intracranial safety signals were identified, including no hemorrhages.

Activity in extrapulmonary NEC and other DLL3-expressing tumors

Thummalapalli presented updated data from a global Phase Ib/II study of zoci in EP-NECs and other DLL3-expressing solid tumors after progression on platinum-based chemotherapy. He said five-year survival in metastatic EP-NEC is less than 15%, with median overall survival of five to eight months, and emphasized that in the second-line setting “there is no established standard of care,” with chemotherapy response rates around 20% and short progression-free survival.

The study included two cohorts: gastroenteropancreatic (GEP) NECs and other EP-NECs (including large cell neuroendocrine carcinoma of the lung, genitourinary or gynecologic NECs, Merkel cell carcinoma, and other DLL3-expressing solid tumors). DLL3 expression was evaluated retrospectively by immunohistochemistry for EP-NEC patients but was not required for enrollment. Thummalapalli said enrollment was evenly split between the U.S. and China, and most patients had advanced-stage disease and high Ki-67 levels.

Among response-evaluable patients, Thummalapalli reported an ORR of 38% to date and a disease control rate of about 56%. ORR was 33% in Cohort 1 (GEP-NECs) and 44% in Cohort 2 (other EP-NECs). He noted tumor reductions across multiple subtypes, while also acknowledging more primary progression in the GEP cohort.

He highlighted a potential signal related to prior topoisomerase-1 exposure: in five patients who previously received irinotecan (all GEP-NEC), “no patients showed a response,” while a patient with cervical NEC previously treated with topotecan achieved a partial response on zoci. He said more data are being generated to understand factors associated with response.

On biomarkers, Thummalapalli said the team has not observed a clear relationship between DLL3 expression and response, noting responses in DLL3-negative patients and activity across a range of expression levels. He said preliminary data “does not support excluding patients” based on negative DLL3 expression, citing the drug’s bystander effect as one possible reason.

Safety in EP-NEC appeared consistent with SCLC experience, he said, with most events low grade and common hematologic and gastrointestinal events including anemia, leukopenia, and nausea. He reported one case of grade 2 interstitial lung disease (ILD) among 46 treated patients and suggested the ILD rate in EP-NEC “seems to be lower” than in SCLC, potentially due to differences in lung tumor burden and prior chest radiation frequency.

Development plans and combination strategy

Amado outlined Zai Lab’s development strategy positioning zoci across multiple settings in SCLC and EP-NEC. For previously treated SCLC, he said the global Phase III DLLEVATE study is ongoing, with expected enrollment completion in the first half of 2027. He added that an interim analysis could position zoci monotherapy for potential accelerated approval in 2028.

In first-line SCLC, Amado said Zai Lab is evaluating zoci in combination with a PD-L1 inhibitor with or without chemotherapy and expects to present combination data, including first-line data, at a conference later in 2026. He said the company expects to initiate a pivotal trial by year-end with the selected combination.

Amado also discussed recently announced collaborations with Amgen and Boehringer Ingelheim (BI) to pursue combinations pairing zoci’s cytotoxic tumor debulking with T-cell engager–driven immune activity, which he said could deepen and extend responses with “minimal overlap in toxicity.” He said Zai Lab has initiated a global Phase Ib study with Amgen evaluating zoci plus tarlatamab, including dose exploration and expansion in both tarlatamab-naïve and tarlatamab-exposed patients, and plans to evaluate a triplet in first-line. He also said the company plans to initiate a global Phase Ib/II study with BI evaluating zoci plus Abraxane in neuroendocrine carcinomas, as well as a triplet with atezolizumab in first-line SCLC and, depending on emerging data, potentially first-line EP-NEC. Amgen and BI will sponsor and lead their respective studies, he said.

Q&A: comparisons, trial design, and blood-brain barrier questions

During Q&A, Paz-Ares said it is still “early days” without robust Phase III data, but argued the intracranial response rates reported—54% overall and 62% at 1.6 mg/kg—appear favorable compared with “standard of care drugs, which are more on the 20%-30%,” calling the results encouraging for future survival and quality-of-life impact.

Amado addressed why DLLEVATE stratifies by baseline brain metastases, saying patients with brain metastases have poorer prognosis and stratification ensures balance between arms, particularly because outcomes in the control arm would differ between those with and without brain involvement.

Asked about concordance between intracranial and systemic responses, Paz-Ares said concordance is “pretty high” and emphasized the key message of the AACR presentation was that brain responses were similar to systemic responses, suggesting no apparent access limitation to induce intracranial responses.

On radiotherapy confounding, Amado said the protocol requires at least a seven-day washout for radiotherapy. Paz-Ares added that the dataset was too small to dissect timing effects in detail, but said response rates were similar in those with prior radiotherapy (50%) and those without (60%), and that baseline post-radiotherapy imaging is required. He and Amado discussed brain metastasis–associated blood-brain barrier disruption as a factor, and Amado added zoci’s “very low nanomolar affinity” binding to DLL3 may contribute to the activity observed.

Additional AACR pipeline highlights

Amado briefly highlighted two additional programs being presented around AACR. He described ZL-1222, an IL-12 PD-1 immunocytokine designed to localize IL-12 signaling to the tumor microenvironment and improve tolerability compared with systemic IL-12. He said preclinical studies showed antitumor activity and a pilot non-human primate toxicology study showed tolerability up to 10 mg/kg, with IND-enabling work planned in 2026.

He also discussed ZL-6201, an LRRC15-targeting ADC with a camptothecin-based topoisomerase-1 payload, citing preclinical tumor growth inhibition in LRRC15-positive sarcoma patient-derived xenograft models and activity in models where LRRC15 is expressed on cancer-associated fibroblasts. Amado said a global Phase I study is underway and that enrollment acceleration is planned in 2026.

About Zai Lab NASDAQ: ZLAB

Zai Lab Ltd NASDAQ: ZLAB is a biopharmaceutical company focused on the research, development, manufacturing and commercialization of innovative therapies. Headquartered in Shanghai, China, Zai Lab operates R&D centers in Asia and the United States and maintains commercial offices across Greater China, North America, Europe and Australia. The company's end-to-end platform encompasses discovery biology, translational development, clinical research and global supply chain management.

The company's marketed portfolio is anchored by Brukinsa (zanubrutinib), a next-generation Bruton's tyrosine kinase inhibitor approved for several B-cell malignancies.

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