— 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, China & CAMBRIDGE, MA, USA I October 24, 2024 I 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.”
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.
SOURCE: Zai Lab
Post Views: 174
— 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, China & CAMBRIDGE, MA, USA I October 24, 2024 I 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.”
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.
SOURCE: Zai Lab
Post Views: 174
