ZL-1310, an Investigational DLL3-Targeted Antibody-Drug Conjugate (ADC), Demonstrates Promising Objective Response Rates and Safety Profile in Extensive-Stage Small Cell Lung Cancer
Zai Lab presented promising Phase 1a/1b study results for ZL-1310, a next-generation antibody-drug conjugate (ADC), in treating extensive-stage Small Cell Lung Cancer. The study showed a 74% objective response rate across all dose levels in previously treated patients. Key findings include positive responses in patients with brain metastases and favorable safety profile with mainly Grade 1 or 2 adverse events. Of 25 patients treated, only 20% experienced Grade ≥3 treatment-related adverse events, with neutropenia being most common. The drug demonstrated efficacy across various DLL3 expression levels, with 13 of 14 responders still on treatment.
Zai Lab ha presentato risultati promettenti dello studio di fase 1a/1b per ZL-1310, un anticorpo coniugato ai farmaci di nuova generazione (ADC), nel trattamento del carcinoma polmonare a piccole cellule in stadio avanzato. Lo studio ha mostrato un 74% di tasso di risposta obiettivo in tutti i livelli di dose in pazienti precedentemente trattati. Le principali scoperte includono risposte positive nei pazienti con metastasi cerebrali e un profilo di sicurezza favorevole, con eventi avversi principalmente di grado 1 o 2. Dei 25 pazienti trattati, solo il 20% ha sperimentato eventi avversi correlati al trattamento di grado ≥3, con la neutropenia risultata la più comune. Il farmaco ha dimostrato efficacia attraverso vari livelli di espressione di DLL3, con 13 dei 14 rispondenti ancora in trattamento.
Zai Lab presentó resultados prometedores del estudio de fase 1a/1b para ZL-1310, un conjugado de anticuerpo-fármaco de nueva generación (ADC), en el tratamiento del cáncer de pulmón de células pequeñas en etapa avanzada. El estudio mostró una tasa de respuesta objetiva del 74% en todos los niveles de dosis en pacientes previamente tratados. Los hallazgos clave incluyen respuestas positivas en pacientes con metástasis cerebrales y un perfil de seguridad favorable, con eventos adversos principalmente de grado 1 o 2. De los 25 pacientes tratados, solo el 20% experimentó eventos adversos relacionados con el tratamiento de grado ≥3, siendo la neutropenia la más común. El fármaco demostró eficacia en varios niveles de expresión de DLL3, con 13 de 14 respondedores aún en tratamiento.
Zai Lab는 진행성 소세포 폐암 치료를 위한 차세대 항체-약물 접합체(ADC)인 ZL-1310의 1a/1b상 연구 결과를 발표했습니다. 연구에 따르면, 이전에 치료를 받은 환자에서는 모든 용량 수준에서 74%의 객관적인 반응률을 보였습니다. 주요 발견으로는 뇌 전이가 있는 환자에서 긍정적인 반응이 있었고, 주로 1등급 또는 2등급의 부작용이 발생해 안전성 프로필이 우수하다는 점입니다. 25명의 치료를 받은 환자 중 20%만이 3등급 이상의 치료 관련 부작용을 경험하였으며, 주로 발생한 부작용은 호중구감소증이었습니다. 이 약물은 다양한 DLL3 발현 수준에서의 효능을 입증하였으며, 14명의 반응자 중 13명이 여전히 치료를 받고 있습니다.
Zai Lab a présenté des résultats prometteurs d'une étude de phase 1a/1b pour ZL-1310, un anticorps-conjugué de nouvelle génération (ADC), dans le traitement du cancer du poumon à petites cellules à un stade avancé. L'étude a montré un taux de réponse objective de 74% à tous les niveaux de dose chez des patients précédemment traités. Les résultats clés incluent des réponses positives chez des patients avec métastases cérébrales et un profil de sécurité favorable, avec principalement des événements indésirables de grade 1 ou 2. Parmi les 25 patients traités, seulement 20% ont éprouvé des événements indésirables liés au traitement de grade ≥3, la neutropénie étant la plus courante. Le médicament a démontré son efficacité à divers niveaux d'expression de DLL3, avec 13 des 14 répondants encore sous traitement.
Zai Lab hat vielversprechende Ergebnisse der Phase 1a/1b-Studie für ZL-1310, ein neuartiges Antikörper-Wirkstoff-Konjugat (ADC), zur Behandlung von fortgeschrittenem kleinzelligem Lungenkrebs präsentiert. Die Studie zeigte eine 74% objektive Ansprechrate über alle Dosierungsstufen bei zuvor behandelten Patienten. Zu den wichtigsten Ergebnissen gehören positive Reaktionen bei Patienten mit Hirnmetastasen und ein günstiges Sicherheitsprofil mit hauptsächlich Grad 1 oder 2 Nebenwirkungen. Von 25 behandelten Patienten erfuhren nur 20% behandlungsbedingte Nebenwirkungen der Grad ≥3, wobei Neutropenie am häufigsten auftrat. Das Medikament zeigte Wirksamkeit bei verschiedenen DLL3-Expressionslevels, wobei 13 von 14 Ansprechenden weiterhin in Behandlung sind.
- High objective response rate of 74% across all dose levels
- 100% response rate in patients with brain metastases
- Strong safety profile with majority of adverse events being Grade 1 or 2
- 13 out of 14 responders remain on treatment
- No treatment discontinuations due to adverse events
- follow-up period of 2.4 months median
- One dose-limiting toxicity observed at 2.4mg/kg dose level
- 20% of patients experienced Grade ≥3 treatment-related adverse events
Insights
The Phase 1a/1b trial results for ZL-1310 show remarkable promise in treating extensive-stage Small Cell Lung Cancer. The
The safety profile appears manageable, with mostly Grade 1-2 adverse events and only
These strong preliminary results could significantly impact Zai Lab's market position in the oncology space. The SCLC market represents a substantial opportunity, with effective treatment options currently available. If ZL-1310 maintains this efficacy profile in larger trials, it could become a leading therapy in this indication. The potential for both monotherapy and combination use across multiple treatment lines expands the commercial opportunity.
The data quality and presentation at a major conference adds credibility and visibility to Zai Lab's development capabilities. This could attract potential partnerships and validate their ADC platform technology, potentially leading to increased institutional investor interest.
-- Objective response rate (ORR) of
-- Favorable pharmacokinetics (PK) and safety profile support continued evaluation of ZL-1310 as a single agent and in combination for the treatment of extensive-stage SCLC in recurrent and first-line therapy
-- Zai Lab to host conference call and webcast to discuss data on October 24, 2024, at 8:30 a.m. ET, following presentation of the data at ENA
Data shared in the ENA presentation from the ongoing Part 1a monotherapy dose-escalation portion of the study included results from 25 patients across four dose cohorts (0.8 mg/kg, 1.6mg/kg, 2.0 mg/kg, and 2.4 mg/kg). Nineteen patients had evaluable tumor assessments.
Key efficacy results include (n=19):
-
The ORR in patients with at least one post-treatment evaluation was
74% (95% CI, 48.8, 90.9). ZL-1310 anti-tumor activity was demonstrated across all dose levels. - Responses were seen in patients with DLL3 H-scores from 5 (range: 5 to 260). No response was observed in a patient whose tumor did not express DLL3.
- Across all cohorts, median length of follow up is 2.4 months making duration of response not estimable. Of the 14 responders, 13 remain on treatment with the longest patient ongoing at 6.5+ months.
- Of the six response-evaluable patients with baseline brain metastases, all achieved a partial response (PR).
- One patient who progressed after prior DLL3 bi-specific therapy achieved PR at the first tumor assessment.
Key safety findings include (n=25):
-
ZL-1310 was well tolerated across all dose levels with the majority of treatment emergent adverse events (TEAE) being Grade 1 or 2. One dose-limiting toxicity (DLT) was observed at 2.4mg/kg (Grade 4 transient neutropenia/thrombocytopenia). Grade ≥3 treatment-related adverse events occurred in five of the 25 patients (
20% ); neutropenia was the most common grade ≥3 event, occurring in three of the 25 patients (12% ). Serious treatment-related adverse events occurred in two patients (8% ); three patients (12% ) required dose reductions, and no patients discontinued treatment due to TEAE.
All patients had progressed following standard platinum-based chemotherapy, and
“The preliminary results from the ongoing Phase 1 trial of ZL-1310 suggest that this next-generation ADC therapy has the potential to deliver anti-tumor responses in the majority of patients with ES-SCLC, with good tolerability,” said Dr. Alex Spira, a medical oncologist at Virginia Cancer Specialists and NEXT Oncology. “This is particularly encouraging given the urgent need for improved treatment options for these patients. These promising data support continued evaluation of ZL-1310 as a monotherapy in the dose-expansion phase of the ongoing Phase 1 clinical trial and in combination.”
“The ZL-1310 clinical program demonstrates Zai Lab’s commitment and ability to pursue novel modalities and validated cancer targets, and to advance innovative global oncology programs,” said Rafael G. Amado, M.D., President, Head of Global Research and Development, Zai Lab. “Based on the encouraging preliminary findings from our Phase 1 trial, we look forward to continuing development of ZL-1310 and advancing this promising asset across lines of therapy as part of our global oncology pipeline.”
Webcast and Conference Call
To access the webcast and conference call on October 24, 2024, at 8:30 a.m. ET, please register at https://register.vevent.com/register/BI6f8ba8dc42d04cd3afd7095cf7c83d40.
All participants must use the link provided above to complete the online registration process in advance of the conference call. Dial-in details will be in the confirmation email which the participant will receive upon registering.
A replay will be available shortly after the call and can be accessed by visiting the Company's website.
About Zai Lab
Zai Lab (NASDAQ: ZLAB; HKEX: 9688; “Zai Lab”) is an innovative, research-based, commercial-stage biopharmaceutical company based in
For additional information about Zai Lab, please visit www.zailaboratory.com or follow us at www.twitter.com/ZaiLab_Global.
About ZL-1310
ZL-1310 is a novel ADC in Zai Lab’s growing, global oncology pipeline that targets Delta-like ligand 3 (DLL3), an antigen that is overexpressed in many neuroendocrine tumors, is typically associated with poor clinical outcomes, and is a validated therapeutic target for SCLC. ZL-1310 comprises a humanized anti-DLL3 monoclonal antibody linked to a novel camptothecin derivative (a topoisomerase 1 inhibitor) as its payload. The compound was designed with a novel ADC technology platform called TMALIN®, which leverages the tumor microenvironment to overcome challenges associated with first-generation ADC therapies, including off-target payload toxicity.
The ongoing Phase 1a/1b clinical trial is evaluating ZL-1310 as monotherapy and in combination with atezolizumab, an immune checkpoint inhibitor, for the treatment of extensive-stage SCLC.
Zai Lab Forward-Looking Statements
This press release contains forward-looking statements relating to our future expectations, plans, and prospects, for Zai Lab, including, without limitation, statements relating to our prospects and plans for developing and commercializing next generation ADCs, including ZL-1310, the potential benefits of ZL-1310, and the potential treatment of SCLC and neuroendocrine tumors. These forward-looking statements may contain words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “plan,” “possible,” “potential,” “will,” “would,” and other similar expressions. Such statements constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are not statements of historical fact or guarantees or assurances of future performance. Forward-looking statements are based on our expectations and assumptions as of the date of this press release and are subject to inherent uncertainties, risks, and changes in circumstances that may differ materially from those contemplated by the forward-looking statements. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including but not limited to (1) our ability to successfully commercialize and generate revenue from our approved products, (2) our ability to obtain funding for our operations and business initiatives, (3) the results of our clinical and pre-clinical development of our product candidates, (4) the content and timing of decisions made by the relevant regulatory authorities regarding regulatory approvals of our product candidates, (5) risks related to doing business in
Our SEC filings can be found on our website at www.zailaboratory.com and on the SEC’s website at www.sec.gov.
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Investor Relations:
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Source: Zai Lab Limited
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