ZL-1218 / ZAI Lab - LARVOL DELTA

KEYNOTE-F22: A Phase 1 Study of ZL-1218 in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=34 | Terminated | Sponsor: Zai Lab (Hong Kong), Ltd. | N=60 ➔ 34 | Trial completion date: Mar 2027 ➔ Aug 2025 | Recruiting ➔ Terminated | Trial primary completion date: Mar 2026 ➔ Aug 2025; Sponsor Decision

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Oncology • Solid Tumor

KEYNOTE-F22: A Phase 1 Study of ZL-1218 in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: Zai Lab (Hong Kong), Ltd. | Active, not recruiting ➔ Recruiting | Trial completion date: Nov 2025 ➔ Mar 2027 | Trial primary completion date: Nov 2024 ➔ Mar 2026

Enrollment open • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

KEYNOTE-F22: A Phase 1 Study of ZL-1218 in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=60 | Active, not recruiting | Sponsor: Zai Lab (Hong Kong), Ltd. | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Oncology • Solid Tumor

Preliminary clinical PK and PD analysis of a phase I study of ZL-1218, a humanized anti-CCR8 IgG1 antibody, in patients with advanced solid tumors (ESMO 2024) - P1 | "ZL-1218 was observed to mediate Foxp3+ Treg depletion in the periphery. In addition, paired tumor biopsies revealed CCR8+ cell depletion and concomitant CD8+ cell increase, suggesting ZL-1218's potential to modulate the TME. These data will be updated in the final poster presentation."

Clinical • Metastases • P1 data • Oncology • Solid Tumor • CCR8 • CD8 • FOXP3

Zai Lab to Present Preliminary Data From Phase 1 Trial of ZL-1218, an Investigational Anti-CCR8 Antibody for the Treatment of Advanced Solid Tumors, at ESMO Congress 2024 (Businesswire) - "Zai Lab Limited...announced that data from a Phase 1 study of ZL-1218, the company’s anti-CCR8 antibody, will be presented in a poster session at the European Society for Medical Oncology (ESMO) Congress 2024 taking place September 13-17, 2024, in Barcelona, Spain. The preliminary results from the ongoing dose-escalation clinical trial (NCT05859464) will highlight the potential of ZL-1218 to reduce regulatory T cells and modulate T-cell function in the tumor microenvironment (TME) of advanced solid tumors."

P1 data • Oncology • Solid Tumor

Zai Lab Announces Second Quarter 2024 Financial Results and Recent Corporate Updates (Businesswire) - "Expected Clinical Development and Data Readouts:...(i) ZL-1310 (DLL3 ADC): Potential dose escalation data from the global Phase 1 study in relapsed and refractory second-line+ SCLC at the end of 2024 or early 2025; (ii) ZL-1218 (CCR8): Present the preliminary clinical PK and PD analysis of the global Phase 1 study in solid tumors at 2024 European Society for Medical Oncology (ESMO) in September 2024."

P1 data • PK/PD data • Small Cell Lung Cancer

Zai Lab-Supported Study Published in Cell Provides New Insights with Potential to Improve Treatment of HRD-Positive Ovarian Cancers, Including Through Combination PARP Inhibitor and CCR8 Therapy (Businesswire) - "Zai Lab Limited...announced that data published in the journal Cell demonstrate that neoadjuvant monotherapy with the poly (ADP-ribose) polymerase (PARP) inhibitor niraparib results in a high response rate and reshapes the tumor microenvironment (TME), providing new targets for immunotherapy and combination regimens in patients with homologous recombination deficiency (HRD) positive ovarian cancer. The study revealed niraparib preferentially suppresses certain immune cells that support the growth of HRD-positive ovarian tumors. This Zai Lab-supported study also showed that targeted clearance of infiltrating regulatory T cells (eTregs) using Zai Lab’s investigational CCR8 antibody, ZL-1218, significantly sensitized niraparib against HRD tumors, resulting in decreased tumor burden in pre-clinical models."

Preclinical • Ovarian Cancer

Trial in progress: A phase I, open-label, multicenter study of ZL-1218, an anti-CCR8 IgG1, as a single agent and as combination therapy with anti-PD-1 antibody to evaluate the safety, tolerability, and pharmacokinetics in subjects with advanced solid tumor (AACR 2024) - "Methods This is a Phase I study of ZL-1218 as a single agent and in combination with pembrolizumab (P) to evaluate the safety, tolerability, pharmacokinetics/pharmacodynamics, and preliminary antitumor activity in subjects with advanced solid tumor malignancies. (2) Subjects with symptomatic or uncontrolled brain metastasis requiring concurrent treatment, impaired major organ functions, active autoimmune disease, or active infections. Part 1 Dose Escalation is ongoing in the US and EU."

Clinical • Combination therapy • IO biomarker • Metastases • PK/PD data • Oncology • Solid Tumor • CCR8

Zai Lab Presentations at AACR 2024 Annual Meeting to Showcase Ongoing Clinical Studies in Key Global Oncology Programs (Businesswire) - "Zai Lab Limited...announced that two poster presentations highlighting ongoing global clinical studies in its oncology pipeline will be presented at the upcoming American Association for Cancer Research (AACR) Annual Meeting 2024 taking place April 5-10, 2024, in San Diego, California. The global oncology programs to be showcased at AACR 2024 include a Phase 1a/1b study of ZL-1310 (NCT06179069), a novel antibody-drug conjugate (ADC) within the Zai Lab pipeline that targets the Delta-like ligand 3 (DLL3), a validated therapeutic target for the treatment of small cell lung cancer (SCLC)....Also featured at AACR 2024 will be Zai Lab’s Phase 1 study (NCT05859464) of ZL-1218, an anti-CCR8 antibody that blocks regulatory T cells (Treg) which suppress antitumor immunity in tumor tissue and is designed to deplete Treg cells selectively in tumors and minimally in other tissue."

Trial status • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Zai Lab Announces First Quarter 2023 Financial Results and Corporate Updates (GlobeNewswire) - "Anticipated Major Milestones in 2023: Odronextamab: Zai Lab partner Regeneron Pharmaceuticals, Inc. (Regeneron) to initiate confirmatory studies in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) including in earlier lines in the second quarter of 2023....ZL-1218: Zai Lab to initiate a global Phase 1 study."

New P1 trial • New trial • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Phase 1 Study of ZL-1218 in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: Zai Lab (Hong Kong), Ltd.

Combination therapy • Metastases • New P1 trial • Oncology • Solid Tumor

ZL-1218 targets the most suppressive intratumoral Treg subpopulation to avoid peripheral toxicities (SITC 2022) - "Conclusions These findings suggest that ZL-1218 antibody may deliver optimal tumor-targeted Treg depletion in the clinic while limiting peripheral toxicities to avoid autoimmune response. Ethics Approval The study was approved by IACUC committee in Zai Lab (US) LLC (Protocol approval number 2020-11_1)."

Clinical • IO biomarker • Oncology • CCR8 • CD4 • CTLA4 • FOXP3 • IL2RA • IL7R • TIGIT

Zai Lab to Present New Oncology Research at 2022 Society for Immunotherapy of Cancer Annual Meeting (GlobeNewswire) - "Zai Lab Limited...will present new data from its internal immuno-oncology pipeline at the upcoming Society for Immunotherapy of Cancer (SITC) Annual Meeting on November 8-12, 2022 in Boston, Mass. These presentations will focus on two key global discovery programs: ZL-1211, an anti-CLDN18.2 antibody and ZL-1218, an anti-CCR8 antibody."

P1/2 data • Preclinical • Oncology • Solid Tumor

ZL-1218, a novel anti-CCR8 antibody, exerts potent antitumor effect by depleting intratumoral regulatory T cells (AACR 2022) - "We are currently exploring the significance of these distinct populations and the impact of ZL-1218-mediated depletion of both CCR8 high- and CCR8 low-expressing subsets in multiple indications. Together, these data support the advancement of ZL-1218 into clinical evaluation as a novel therapeutic candidate to treat human solid tumors."

IO biomarker • Oncology • Solid Tumor • CCR8 • CD4 • FOXP3

Zai Lab to Present New Oncology Research at 2022 AACR Annual Meeting (GlobeNewswire) - "For the first time, Zai Lab will present data on ZL-1218, a novel antibody that targets the CCR8 receptor selectively expressed on resident regulatory T-cells (Tregs) in solid tumors. This oral presentation will highlight the discovery and development of this therapeutic, including the antitumor activity of ZL-1218 in an animal model, as a single agent and in combination with anti-PD-1. This presentation provides preclinical data supporting ZL-1218 as a potential clinical therapeutic candidate for solid tumors."

Preclinical • Oncology • Solid Tumor

Zai Lab Announces Financial Results and Corporate Updates for Twelve Months Ended December 31, 2021 (GlobeNewswire) - "Anticipated 2022 Zai Milestone: Simurosertib: Initiate a Phase 2 biomarker-driven proof-of-concept study in the second quarter of 2022; ZL-1201: Determine a recommended Phase 2 dose in the ongoing Phase 1 trial in mid-2022; Present preclinical data of ZL-1201 in combination with standard of care therapeutic antibodies in hematologic and solid tumor models at the 2022 AACR annual meeting; ZL-1211: Present preclinical data of ZL-1211 (Claudin18.2), ZL-2201 (DNA-PK), and ZL-1218 (CCR8) at the 2022 AACR annual meeting."

Clinical • New P2 trial • Preclinical • Hematological Malignancies • Oncology • Solid Tumor