"Cornerstone therapy" potential highly recognized, ZAI LAB (09688) zoci continues to expand future value boundaries

Title context: "Cornerstone therapy" potential highly recognized, ZAI LAB (09688) zoci continues to expand future value boundaries Text: Recently, the 2026 European Society for Medical Oncology (ESMO) Congress was held in Madrid, Spain, attracting widespread attention from the international academic community, and global secondary market investors are also actively seeking investment opportunities therein. It was observed that on October 23, ZAI LAB's US stock price rose sharply, with intraday gains reaching as high as 11.12% that day; its trading volume that day reached 3.6915 million shares, a new high in nearly 2 months, corresponding to a turnover of US$86.9231 million, reflecting significantly heated trading enthusiasm in the market. The reason for the positive reaction in the secondary market is that the company announced at that day's ESMO Congress the first data from a global Phase Ib clinical study evaluating zocilurtatug pelitecan (Zoci, formerly ZL-1310) in combination with atezolizumab (with or without carboplatin) for first-line treatment of extensive-stage small cell lung cancer (ES-SCLC). Its stunning data results have won widespread recognition from the global academic community and capital markets, and also filled investors with expectations for the product's future global commercialization prospects. Investment bank Cantor published a research report stating that the data Zai Lab's DLL3 ADC zoci announced this time in first-line extensive-stage small cell lung cancer has reached "Home Run" level, and thoracic oncology experts from NYU Grossman School of Medicine who participated in the discussion are optimistic that zoci can replace first-line chemotherapy, has the potential to change the first-line treatment landscape, and gradually grow into a cornerstone therapy (Backbone Therapy) for small cell lung cancer treatment. Stunning clinical data, taking another step toward "chemotherapy-free" As a DLL3-targeting ADC drug independently developed internally by ZAI LAB and with global clinical development independently advanced, and also one of the fastest-advancing DLL3 ADCs globally, Zoci has been highly exposed at international authoritative conferences since entering Phase I clinical trials, and has demonstrated broad therapeutic prospects in the fields of small cell lung cancer and neuroendocrine tumors. In less than two years, Zai Lab advanced zoci from the first-in-human (FIH) investigational new drug (IND) application to the global Phase III registrational study stage, and obtained orphan drug designation and fast track designation from the US FDA, orphan drug designation from the European EMA, and breakthrough therapy designation from China's National Medical Products Administration, fully demonstrating that it has gained unanimous recognition from the global industry and authoritative regulatory agencies, and also reflecting the outstanding collaboration capabilities and clinical development efficiency of Zai Lab's global team. Against this backdrop, ZAI LAB bringing Zoci's latest research results in first-line treatment of small cell lung cancer to this year's ESMO Annual Meeting undoubtedly became the focus of industry attention. It is understood that the data announced by Zai Lab this time came from a global Phase Ib study evaluating Zoci in combination with atezolizumab for first-line treatment of extensive-stage small cell lung cancer (ES-SCLC), with two regimens: a chemotherapy-free "dual-drug regimen" (Zoci + atezolizumab), and a "triple-drug regimen" adding carboplatin on this basis. The dual-drug regimen is the core of this data. At the recommended Phase III study dose (RP3D) of 1.6 mg/kg (n=33), the confirmed objective response rate (ORR) of the dual-drug regimen reached 81.8%, and the 6-month progression-free survival rate was 81.9%. Responses not only came quickly but also lasted. Among 15 patients followed for at least 6 months, at a median follow-up of 10 months, both median progression-free survival (mPFS) and median duration of response (mDoR) had not yet been reached, with 10 patients (66.7%) still free of disease progression. Safety is also a highlight of the dual-drug regimen. At the 1.6 mg/kg dose, adverse events related to Zoci were mostly Grade 1 or Grade 2; the incidence of Grade 3 adverse events (TRAE) related to Zoci was only 9.1%, with no treatment-related discontinuations and no treatment-related deaths, and only 1 case of interstitial lung disease (ILD)/non-infectious pneumonitis, which was Grade 1. As a comparison, the triple-drug regimen (n=13, pooled across multiple dose levels) had a confirmed ORR of 92.3%, mPFS of 8.4 months, and mDoR of 7.7 months. But after adding carboplatin, toxicity increased significantly: the incidence of Grade 3 treatment-emergent adverse events (TEAE) rose from 21.2% with the dual-drug regimen to 76.9%, mainly hematologic toxicity. In short, the chemotherapy-free dual-drug regimen achieved a better balance among efficacy, durability, and safety; while adding platinum-based chemotherapy exchanged for a higher response rate but also brought a significantly heavier burden of hematologic toxicity. This is also the reason why the dual-drug regimen became the focus of subsequent development. In fact, the current standard of care for first-line small cell lung cancer is immune checkpoint inhibitors combined with chemotherapy, with a response rate of 60-70%, median progression-free survival of about 5 months, and accompanied by about 60% Grade 3 or higher treatment-related adverse events. By comparison (cross-trial indirect comparison, not head-to-head), the data performance of Zoci combined with atezolizumab dual-drug regimen in the complete absence of chemotherapy conveys a key signal: a chemotherapy-free regimen based on Zoci is expected to deliver better safety and more durable disease control while achieving efficacy not inferior to platinum-containing chemotherapy, pushing first-line treatment of ES-SCLC one step further toward "chemotherapy-free." This approach has also extended to combination development. It is understood that this year, ZAI LAB has entered into a global clinical research collaboration with Amgen to evaluate zoci in combination with IMDELLTRA (tarlatamab, a DLL3/CD3 bispecific TCE) for extensive-stage small cell lung cancer; and entered into a clinical research collaboration with Boehringer Ingelheim to evaluate Zoci in combination with Obrixtamig (a DLL3/CD3 bispecific TCE) for small cell lung cancer and other neuroendocrine cancers. Two multinational pharmaceutical companies holding DLL3 TCEs successively choosing to combine with Zoci has a mechanistic basis: Zoci directly kills tumor cells by ADC internalization and payload release, independent of T cells, and complements the killing pathway of T-cell engagers. This also indirectly reflects that Zoci leads in development in the DLL3 ADC field and has the potential to serve as a cornerstone drug for combination therapy. Global development leadership, continuously expanding the boundaries of clinical value From a market perspective, the global lung cancer treatment market is currently continuing to expand and is expected to grow to US$76.6 billion by 2030, with small cell lung cancer accounting for about 15% of global confirmed lung cancer cases. Among the approximately 250,000 new SCLC cases globally each year, about two-thirds are already at extensive stage (ES-SCLC) at diagnosis, and they also face a severe burden of brain metastases. Although first-line immunotherapy combined with chemotherapy has raised the median overall survival (OS) of ES-SCLC to 12-15 months, long-term survival rates remain extremely low, with the 5-year survival rate hovering at only 5%-10%. It can thus be seen that there is still very large room for improvement in the treatment of small cell lung cancer, especially extensive-stage small cell lung cancer, and clinical needs are very urgent. In recent years, targets such as DLL3, B7-H3, and SEZ6 that are highly expressed on SCLC tumor cells have been successively discovered, becoming important directions for ADC development and giving rise to a batch of highly promising ADC candidate drugs. Among them, DLL3 is highly expressed in SCLC and lowly expressed in normal tissues, and is considered one of the targets with relatively strong specificity. Zoci is precisely one of the globally leading ADCs in development on this target. From the perspective of development progress, Zoci took less than two years to advance from the first-in-human IND to global Phase III studies, and both second-line and first-line have entered or are about to enter global registrational studies, with R&D and regulatory progress in the first tier of global first-line SCLC competition. It is understood that ZAI LAB plans to submit the marketing application for Zoci's first indication to the US FDA in 2027. If progress goes smoothly, Zoci is expected to become the world's first approved DLL3 ADC. Conclusion The data announced at this ESMO Annual Meeting show that Zoci combined with atezolizumab's chemotherapy-free regimen combines a high response rate, positive durability signals, and outstanding safety, providing strong early evidence for its entry into first-line ES-SCLC and for advancing "chemotherapy-free" treatment. Whether it can become the "cornerstone therapy" for first-line small cell lung cancer will ultimately depend on Phase III overall survival data to answer. But this ESMO data at least show that replacing first-line chemotherapy with a safer ADC is no longer merely an idea. From second-line to first-line, from monotherapy to combination, Zoci's development path is gradually becoming clearer.