On October 24, 2024 Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) reported 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 (Free EORTC-NCI-AACR Whitepaper) (ENA) Symposium 2024 in Barcelona, Spain, as an oral presentation during the plenary session (Press release, Zai Laboratory, OCT 24, 2024, View Source [SID1234647391]). 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.

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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.

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