Zai Lab reports strong, rapid brain metastasis responses with Zocilurtatug Pelitecan in SCLC and other neuroendocrine cancers
Zai Lab Limited has unveiled compelling new clinical and preclinical data highlighting the potential of its oncology pipeline, led by zocilurtatug pelitecan (zoci, formerly ZL-1310), a DLL3-targeting antibody-drug conjugate (ADC). The findings, presented at the American Association for Cancer Research Annual Meeting 2026 in San Diego, underscore the therapy’s promising activity in patients with extensive-stage small cell lung cancer (ES-SCLC) and brain metastases, as well as in other aggressive neuroendocrine carcinomas (NECs). Collectively, the data reinforce Zai Lab’s broader ambition to advance innovative cancer therapies for patient populations with limited treatment options and poor prognoses.
Zoci represents a next-generation ADC designed to selectively target DLL3, a protein commonly overexpressed in small cell lung cancer and other neuroendocrine malignancies. By delivering a cytotoxic payload directly to cancer cells, the therapy aims to maximize anti-tumor activity while minimizing systemic toxicity. The latest clinical data suggest that this targeted approach may be particularly effective in addressing one of the most challenging aspects of ES-SCLC: the development of brain metastases.
Brain metastases are a frequent and devastating complication in patients with ES-SCLC, often driving disease progression and significantly limiting survival. Historically, treatment options for such patients have been inadequate, with therapies such as radiotherapy offering only modest benefits while delaying systemic treatment. Against this backdrop, the results from Zai Lab’s ongoing global Phase 1 clinical trial (NCT06179069) provide a notable advancement.
The study evaluated zoci as a monotherapy administered intravenously every three weeks across multiple dose levels ranging from 0.8 mg/kg to 2.8 mg/kg. With a median follow-up of 7.9 months, the trial demonstrated that zoci induced rapid and substantial regression of intracranial lesions in patients whose cancer had spread to the brain. Importantly, these responses were assessed using modified Response Assessment in Neuro-Oncology for Brain Metastases (mRANO-BM) criteria by an independent radiologic review committee, lending robustness to the findings.
Among the 136 patients treated in the study, 36 percent presented with baseline brain metastases. Within this subgroup, patients who completed at least two post-baseline scans achieved an intracranial objective response rate (iORR) of 53.7 percent, including seven complete responses. At the 1.6 mg/kg dose level, which is emerging as a key therapeutic dose, the confirmed iORR increased to 62.5 percent, with four patients achieving complete intracranial responses.
These results are particularly significant given the historical difficulty of achieving meaningful responses in brain metastases from small cell lung cancer. Moreover, intracranial tumor reductions were observed across multiple dose levels, suggesting consistent activity of the therapy. Notably, responses were seen regardless of whether patients had previously received intracranial radiotherapy, with response rates of 50 percent in previously treated patients and 60 percent in those who had not undergone such treatment. This finding indicates that zoci may provide therapeutic benefit independent of prior interventions, potentially expanding its applicability across diverse patient populations.
The safety profile of zoci in this trial was also encouraging. Most treatment-emergent adverse events were reported as low grade, and treatment discontinuations were minimal. Grade 3 or higher treatment-related adverse events occurred in 19.9 percent of patients overall and in 16.4 percent of patients receiving the 1.6 mg/kg dose. The most common high-grade adverse events included neutropenia, anemia, thrombocytopenia, lymphopenia, and leukopenia—findings consistent with the known effects of cytotoxic therapies. Importantly, no treatment-related neurological serious adverse events or complications related to intracranial metastases were observed, a critical consideration for therapies targeting brain lesions.
According to Luis Paz-Ares, MD, PhD, senior investigator and Chair of the Medical Oncology Department at Hospital Universitario 12 de Octubre and Head of the Lung Cancer Unit at Spanish National Cancer Research Center, the results represent a meaningful step forward in addressing a major unmet need. He emphasized that patients with ES-SCLC and brain metastases typically face poor outcomes and limited effective treatment options. The ability of zoci to generate rapid and robust responses across multiple dose cohorts, regardless of prior radiotherapy, suggests that it could emerge as a novel therapeutic option for this challenging disease setting.
In addition to the ES-SCLC data, Zai Lab also presented preliminary findings from an ongoing Phase 1b/2 trial (NCT06885281) evaluating zoci in patients with extrapulmonary neuroendocrine carcinomas (epNECs) and other selected solid tumors. These malignancies are often aggressive, associated with poor prognosis, and lack effective standard-of-care therapies, particularly in previously treated patients.
In this study, zoci was administered intravenously at a dose of 1.6 mg/kg every three weeks until disease progression or unacceptable toxicity. The data cutoff for the current analysis was February 18, 2026, with a median follow-up of 3.7 months in the Phase 1b portion. Among 46 patients who had previously received platinum-based chemotherapy and other systemic treatments, zoci demonstrated encouraging anti-tumor activity across multiple epNEC subtypes.
Among response-evaluable patients, the overall response rate (ORR) was 38.2 percent, with 13 out of 34 patients achieving a confirmed response. The disease control rate, which includes patients with stable disease in addition to those with tumor shrinkage, reached 55.9 percent. These findings are particularly noteworthy given the absence of approved standard therapies for previously treated epNEC, highlighting the potential of zoci to fill a critical therapeutic gap.
The safety profile observed in this patient population was consistent with earlier findings. Neutrophil count decrease was the only Grade 3 or higher treatment-related adverse event occurring in more than one patient, reported in 5.2 percent of cases. Overall, the therapy was well tolerated, supporting its continued development in this difficult-to-treat population.
Beyond clinical results for zoci, Zai Lab also presented preclinical data for two additional pipeline candidates: ZL-6201, an LRRC15-targeting ADC, and ZL-1222, a novel immunotherapy combining PD-1 inhibition with IL-12 activity. These programs reflect the company’s commitment to building a diverse and innovative oncology portfolio that leverages multiple therapeutic modalities to address cancer’s complexity.
Rafael G. Amado, MD, President and Head of Global Research and Development at Zai Lab, highlighted the significance of these developments. He noted that the breadth and diversity of the company’s pipeline demonstrate its strategic focus on delivering transformative therapies through a globally integrated research and development model. He also emphasized the rapid advancement of zoci into pivotal development, with plans to initiate three registration-enabling studies by the end of the year.
This accelerated progress is enabled by Zai Lab’s unique operational structure, which integrates capabilities across the United States and China. By combining global scientific expertise with efficient development pathways, the company aims to bring innovative treatments to patients more quickly without compromising quality.
The data presented at AACR 2026 position zoci as a promising candidate in the evolving landscape of targeted oncology therapies. Its demonstrated ability to achieve meaningful intracranial responses in ES-SCLC patients with brain metastases addresses a critical unmet need, while its activity in neuroendocrine carcinomas suggests broader applicability across multiple tumor types.
As the clinical development program advances, further studies will be essential to confirm these findings, evaluate long-term outcomes, and establish the therapy’s role in standard treatment regimens. However, the current results provide a strong foundation for continued optimism, particularly for patients with aggressive cancers who have historically had few effective options.
In an era where precision medicine and targeted therapies are reshaping oncology, zoci exemplifies the potential of antibody-drug conjugates to deliver potent, tumor-specific treatment. If ongoing and future trials validate its efficacy and safety, it could represent a significant step forward in improving outcomes for patients with small cell lung cancer, neuroendocrine carcinomas, and potentially other DLL3-expressing malignancies.
Ultimately, Zai Lab’s latest data highlight not only the promise of a single therapeutic candidate but also the broader impact of innovation in cancer research. By advancing therapies that address critical gaps in care, the company is contributing to a future in which even the most challenging cancers may become more manageable—and, potentially, more survivable.
About Zocilurtatug Pelitecan (Zoci, ZL-1310)
Zoci targets DLL3, a validated therapeutic target for small cell lung cancer that is overexpressed in many neuroendocrine tumors and is generally associated with poor clinical outcomes. Zoci is on track to potentially become Zai Lab’s first global oncology launch, with plans for three registration-enabling studies across 2L+ SCLC, 1L SCLC and extrapulmonary neuroendocrine carcinomas by the end of 2026.
Its potential best-in-class safety profile, coupled with compelling systemic and intracranial efficacy, supports its potential role as a new standard of care in previously treated extensive stage small cell lung cancer, as well as a backbone DLL3-targeting antibody drug conjugate in first line combination regimens, including those that reduce the burdens of chemotherapy, such as check point inhibitors and T-cell engagers.
About ZL-6201
Zai Lab is evaluating ZL-6201 as a potential first-in-class LRRC15-targeting antibody drug conjugate for the treatment of multiple solid tumors. LRRC15 is a type I transmembrane protein and an attractive target for cancer therapy because it is overexpressed in various mesenchymal tumors, such as sarcoma, glioblastoma and melanoma, as well as in cancer associated fibroblasts across many other tumor types.
About ZL-1222
Zai Lab is evaluating ZL-1222 as a potential next-generation bispecific immunocytokine comprising anti-PD-1 and attenuated IL-12 for cancer immunotherapy across multiple indications, with potential to combine potent antitumor activity with improved systemic safety. Previously, interleukin-12 therapies have shown potential benefit across a range of cancer types; however, narrow therapeutic windows and toxicity concerns have limited the utility of this therapeutic class.
About Zai Lab
Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) is an innovative, research-based, commercial-stage biopharmaceutical company based in China and the United States. We are focused on discovering, developing, and commercializing innovative products that address medical conditions with significant unmet needs in the areas of oncology, immunology, neuroscience, and infectious disease. Our goal is to leverage our competencies and resources to positively impact human health.
Source Link:https://www.businesswire.com/
