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

Rhea-AI Summary

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.

Positive

• 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

Negative

• 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

Medical Research Analyst

The Phase 1a/1b trial results for ZL-1310 show remarkable promise in treating extensive-stage Small Cell Lung Cancer. The 74% objective response rate across all dose levels is particularly impressive for this aggressive cancer type, especially considering these were heavily pretreated patients. The drug demonstrates efficacy even in patients with brain metastases, a historically challenging area to treat.

The safety profile appears manageable, with mostly Grade 1-2 adverse events and only 20% of patients experiencing Grade ≥3 treatment-related events. The low discontinuation rate and minimal dose reductions suggest good tolerability. The drug's activity across various DLL3 expression levels indicates potential broad applicability, though confirmation in larger trials is needed.

Financial Analyst

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 74% across all tested dose levels of ZL-1310 in patients with recurrent extensive-stage small cell lung cancer (SCLC)

-- 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

SHANGHAI & CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) today presented data from the ongoing global Phase 1a/1b study of ZL-1310, a potential best-in-class next-generation antibody-drug conjugate (ADC), at the EORTC-NCI-AACR (ENA) Symposium 2024 in Barcelona, Spain, as an oral presentation during the plenary session. ZL-1310 is being tested in patients with previously treated extensive-stage Small Cell Lung Cancer (ES-SCLC) after at least one prior platinum-based chemotherapy regimen.

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 92% of patients progressed after immune checkpoint inhibitors. Fifty-six percent had failed at least two prior lines of therapy. Twenty-eight percent of patients had brain metastases at baseline. At the time of the data cutoff, Oct. 10, 2024, 19 patients had at least one post-baseline tumor assessment per RECIST v1.1. DLL3 expression H-scores were assessed in 16 out of 19 patients.

“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 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 in China and worldwide.

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 China, and (6) other factors identified in our most recent annual and quarterly reports and in other reports we have filed with the U.S. Securities and Exchange Commission (SEC). We anticipate that subsequent events and developments will cause our expectations and assumptions to change, and we undertake no obligation to update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise, except as may be required by law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release.

Our SEC filings can be found on our website at www.zailaboratory.com and on the SEC’s website at www.sec.gov.

View source version on businesswire.com: https://www.businesswire.com/news/home/20241024949177/en/

Investor Relations:

Christine Chiou / Lina Zhang

+1 (917) 886-6929 / +86 136 8257 6943

christine.chiou1@zailaboratory.com / lina.zhang@zailaboratory.com

Media:

Shaun Maccoun/ Xiaoyu Chen

+1 (857) 270-8854 / +86 185 0015 5011

shaun.maccoun@zailaboratory.com / xiaoyu.chen@zailaboratory.com

Source: Zai Lab Limited

FAQ

What is the objective response rate for ZL-1310 in SCLC patients?

ZL-1310 demonstrated a 74% objective response rate (ORR) across all tested dose levels in patients with recurrent extensive-stage small cell lung cancer.

How effective is ZLAB's ZL-1310 in patients with brain metastases?

All six response-evaluable patients with baseline brain metastases achieved a partial response (PR) to ZL-1310 treatment.

What are the main safety concerns with ZL-1310 treatment?

The main safety concern was Grade ≥3 treatment-related adverse events occurring in 20% of patients, with neutropenia being the most common, affecting 12% of patients.

How long have patients been responding to ZL-1310 treatment?

Of the 14 responders, 13 remain on treatment with the longest patient ongoing at 6.5+ months, though median duration of response is not yet estimable due to short follow-up.