A Phase 1 Study of ZL-1218 in Subjects With Advanced Solid Tumors

A Phase I, Open-label, Multicenter Study of ZL-1218 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 Malignancies

The purpose of this study is to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of ZL-1218 as a single agent and as combination therapy in subjects with advanced solid tumor malignancies.

Study Overview

• Status: Terminated
• Conditions: Malignant Solid Tumor
• Intervention / Treatment: Drug: ZL-1218; Drug: Pembrolizumab

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Hangzhou, China, 310009
    • Zai Lab Site 1002
  • Shanghai, China, 200123
    • Zai Lab Site 1001
• Spain
  • Barcelona
    • Barcelona, Barcelona, Spain, 8023
      • Zai Lab Site 8005
    • Barcelona, Barcelona, Spain, 8035
      • Zai Lab Site 8001
  • Madrid
    • Madrid, Madrid, Spain, 28040
      • Zai Lab Site 8007
    • Madrid, Madrid, Spain, 28050
      • Zai Lab Site 8008
    • Pozuelo de Alarcón, Madrid, Spain, 28223
      • Zai Lab Site 8004
  • Sevilla
    • Seville, Sevilla, Spain, 41009
      • Zai Lab Site 8003
  • Valencia
    • Valencia, Valencia, Spain, 46009
      • Zai Lab Site 8002
    • Valencia, Valencia, Spain, 46010
      • Zai Lab Site 8006
• United States
  • California
    • Irvine, California, United States, 92618
      • Zai Lab Site 2005
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Zai Lab Site 2007
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Zai Lab Site 2001
  • New York
    • New York, New York, United States, 10029
      • Zai Lab Site 2002
  • Washington
    • Spokane, Washington, United States, 99208
      • Zai Lab Site 2003

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult men and women ≥ 18 years of age. If 18 years is not the age of majority, then adult men and women ≥ age of majority per local regulation.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Life expectancy > 12 weeks.
• Subjects must have histologically confirmed and documented diagnosis of locally advanced unresectable or metastatic advanced solid tumor that is refractory to standard treatment, or intolerant to standard treatment, or for which no standard treatment exists.Subjects must have at least one target lesion as defined by RECIST v1.1 on CT, PET/CT, or MRI scan.
• Subjects must have a site of disease which is not previously irradiated and is safe and amenable to biopsy per the treating institution's guidelines. Subjects must be willing to undergo a tumor biopsy at screening and on treatment, per the protocol guidelines.
• Subjects must have a site of disease which is not previously irradiated and is safe and amenable to biopsy per the treating institution's guidelines. Subjects must be willing to undergo a tumor biopsy at screening and on treatment, per the protocol guidelines.

Exclusion Criteria:

• Symptomatic or uncontrolled brain metastasis requiring concurrent treatment, inclusive of but not limited to surgery, radiation, and/or corticosteroids.
• Prior exposure to CCR8 inhibitor (anti-CCR8 antibody) or hypersensitivity to any ingredient of the study drug.
• Out of range value within 10 days prior to the first dose of study treatment.
• Subjects have received a live or live-attenuated vaccine within 30 days of planned start of study therapy.
• Subjects with known history of, or any evidence of active, non-infectious pneumonitis.
• Impaired cardiac function or clinically significant cardiac disease within the last 3 months before administration of the first dose of the study drug.
• Treatment with any systemic anti-cancer treatment (including investigational products) within 4 weeks before first dose of study drug.
• Non-palliative radiotherapy within 2 weeks prior to first dose of study drug or have had history of radiation pneumonitis.
• Major surgery within 4 weeks of the first dose of study drug.
• Infections requiring systemic antibiotic therapy.
• Any medical conditions that would, in the investigator's judgement, prevent the subject's participation in the clinical study due to safety concerns, compliance with the study procedures, or interpretation of the study results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Dose Escalation; ZL-1218; Drug: ZL-1218 ZL-1218 dose escalation	Drug: ZL-1218; ZL-1218 dose escalation
Experimental: Part 1: Dose Escalation; ZL-1218 in combination with Pembrolizumab; Drug: ZL-1218 ZL-1218 dose escalation Drug: Pembrolizumab (KEYTRUDA®) Combination treatment with ZL-1218	Drug: ZL-1218; ZL-1218 dose escalation; Drug: Pembrolizumab; Combination treatment with ZL-1218
Experimental: Part 2: Cohort Expansion; Prior CPI Therapy; Drug: ZL-1218 ZL-1218 recommended dose Drug: Pembrolizumab (KEYTRUDA®) Combination treatment with ZL-1218	Drug: ZL-1218; ZL-1218 dose escalation; Drug: Pembrolizumab; Combination treatment with ZL-1218
Experimental: Part 2: Cohort Expansion; CPI therapy Naive; Drug: ZL-1218 ZL-1218 recommended dose Drug: Pembrolizumab (KEYTRUDA®) Combination treatment with ZL-1218	Drug: ZL-1218; ZL-1218 dose escalation; Drug: Pembrolizumab; Combination treatment with ZL-1218

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Dose Limiting Toxicities	Number of subjects with dose limiting toxicities (DLTs) through dose escalation only.	Approximately 24 months
Incidence of Treatment Emergent Adverse Events	Number of subjects with treatment-emergent adverse effects through dose escalation and expansion.	Approximately 24 months
Incidence of Serious adverse events	Number of subjects with Serious Adverse Events through dose escalation and expansion.	Approximately 24 months
Clinically Significant changes in safety assessments	Changes in safety assessment parameters (e.g., vital signs, electrocardiograms [ECGs], and clinical laboratory results) through dose escalation and expansion.	Approximately 24 months
ORR per RECIST 1.1	Objective Response Rate (ORR) per RECIST 1.1 through dose expansion only.	up to 24 months
ORR per iRECIST	Objective Response Rate per iRECIST through dose expansion only.	up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR per RECIST 1.1	Objective Response Rate (ORR) per RECIST 1.1 through dose escalation only.	up to 24 months
ORR per iRECIST	Objective Response Rate (ORR) per iRECIST through dose escalation only.	up to 24 months
Duration of Response per RECIST 1.1	Duration of Response per RECIST 1.1 through dose escalation and expansion.	up to 24 months
Duration of Response per iRECIST	Duration of Response per iRECIST through dose escalation and expansion.	up to 24 months
PFS per RECIST 1.1	Progression-Free Survival (PFS) per RECIST 1.1 through dose escalation and expansion.	up to 24 months
PFS per iRECIST	Progression-Free Survival (PFS) per iRECIST through dose escalation and expansion.	up to 24 months
DCR per RECIST 1.1	Disease Control Rate (DCR) per RECIST 1.1 through dose escalation and expansion.	up to 24 months
DCR per iRECIST	Disease Control Rate (DCR) per iRECIST through dose escalation and expansion.	up to 24 months
Overall Survival	Overall Survival (OS) through dose escalation and expansion.	up to 24 months
Pharmacokinetics (PK): AUC	Area under curve (AUC) through dose escalation and expansion.	up to 24 months
Pharmacokinetics (PK): Cmax	Maximum serum concentration (CMax) through dose escalation and expansion.	up to 24 months
Pharmacokinetics (PK): Tmax	Time to reach Cmax (Tmax) through dose escalation and expansion.	up to 24 months
Pharmacokinetics (PK): Ctrough	Ctrough through dose escalation and expansion.	up to 24 months
Pharmacokinetics (PK): Vss	Volume of distribution as steady state (Vss) through dose escalation and expansion.	up to 24 months
Pharmacokinetics (PK): CL	Clearance (CL) through dose escalation and expansion.	up to 24 months
Pharmacokinetics (PK): t1/2	Half-life (t1/2) through dose escalation and expansion.	up to 24 months
Immunogenicity	Incidence of anti-drug antibodies (ADAs) through dose escalation and expansion.	up to 24 months
Immunogenicity	Quantity of anti-drug antibodies (ADAs) through dose escalation and expansion.	up to 24 months

Collaborators and Investigators

• Sponsor: Zai Lab (Hong Kong), Ltd.
• Collaborators: Merck Sharp & Dohme LLC; Zai Biopharmaceutical (Shanghai) Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2023
• Primary Completion (Actual): August 28, 2025
• Study Completion (Actual): August 28, 2025

Study Registration Dates

• First Submitted: March 17, 2023
• First Submitted That Met QC Criteria: May 4, 2023
• First Posted (Actual): May 16, 2023

Study Record Updates

• Last Update Posted (Actual): October 20, 2025
• Last Update Submitted That Met QC Criteria: October 14, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; pembrolizumab
• Other Study ID Numbers: ZL-1218-001; KEYNOTE-F22, MK-3475-F22 (Other Identifier: Merck Sharpe & Dohme, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No