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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05859464
Recruitment Status : Recruiting
First Posted : May 16, 2023
Last Update Posted : May 10, 2024
Sponsor:
Collaborators:
Zai Biopharmaceutical (Shanghai) Co., Ltd.
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Zai Lab (Hong Kong), Ltd.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Malignant Solid Tumor Drug: ZL-1218 Drug: Pembrolizumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : July 24, 2023
Estimated Primary Completion Date : November 2024
Estimated Study Completion Date : November 2025

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Incidence of Dose Limiting Toxicities [ Time Frame: Approximately 24 months ]
    Number of subjects with dose limiting toxicities (DLTs) through dose escalation only.

  2. Incidence of Treatment Emergent Adverse Events [ Time Frame: Approximately 24 months ]
    Number of subjects with treatment-emergent adverse effects through dose escalation and expansion.

  3. Incidence of Serious adverse events [ Time Frame: Approximately 24 months ]
    Number of subjects with Serious Adverse Events through dose escalation and expansion.

  4. Clinically Significant changes in safety assessments [ Time Frame: Approximately 24 months ]
    Changes in safety assessment parameters (e.g., vital signs, electrocardiograms [ECGs], and clinical laboratory results) through dose escalation and expansion.

  5. ORR per RECIST 1.1 [ Time Frame: up to 24 months ]
    Objective Response Rate (ORR) per RECIST 1.1 through dose expansion only.

  6. ORR per iRECIST [ Time Frame: up to 24 months ]
    Objective Response Rate per iRECIST through dose expansion only.


Secondary Outcome Measures :
  1. ORR per RECIST 1.1 [ Time Frame: up to 24 months ]
    Objective Response Rate (ORR) per RECIST 1.1 through dose escalation only.

  2. ORR per iRECIST [ Time Frame: up to 24 months ]
    Objective Response Rate (ORR) per iRECIST through dose escalation only.

  3. Duration of Response per RECIST 1.1 [ Time Frame: up to 24 months ]
    Duration of Response per RECIST 1.1 through dose escalation and expansion.

  4. Duration of Response per iRECIST [ Time Frame: up to 24 months ]
    Duration of Response per iRECIST through dose escalation and expansion.

  5. PFS per RECIST 1.1 [ Time Frame: up to 24 months ]
    Progression-Free Survival (PFS) per RECIST 1.1 through dose escalation and expansion.

  6. PFS per iRECIST [ Time Frame: up to 24 months ]
    Progression-Free Survival (PFS) per iRECIST through dose escalation and expansion.

  7. DCR per RECIST 1.1 [ Time Frame: up to 24 months ]
    Disease Control Rate (DCR) per RECIST 1.1 through dose escalation and expansion.

  8. DCR per iRECIST [ Time Frame: up to 24 months ]
    Disease Control Rate (DCR) per iRECIST through dose escalation and expansion.

  9. Overall Survival [ Time Frame: up to 24 months ]
    Overall Survival (OS) through dose escalation and expansion.

  10. Pharmacokinetics (PK): AUC [ Time Frame: up to 24 months ]
    Area under curve (AUC) through dose escalation and expansion.

  11. Pharmacokinetics (PK): Cmax [ Time Frame: up to 24 months ]
    Maximum serum concentration (CMax) through dose escalation and expansion.

  12. Pharmacokinetics (PK): Tmax [ Time Frame: up to 24 months ]
    Time to reach Cmax (Tmax) through dose escalation and expansion.

  13. Pharmacokinetics (PK): Ctrough [ Time Frame: up to 24 months ]
    Ctrough through dose escalation and expansion.

  14. Pharmacokinetics (PK): Vss [ Time Frame: up to 24 months ]
    Volume of distribution as steady state (Vss) through dose escalation and expansion.

  15. Pharmacokinetics (PK): CL [ Time Frame: up to 24 months ]
    Clearance (CL) through dose escalation and expansion.

  16. Pharmacokinetics (PK): t1/2 [ Time Frame: up to 24 months ]
    Half-life (t1/2) through dose escalation and expansion.

  17. Immunogenicity [ Time Frame: up to 24 months ]
    Incidence of anti-drug antibodies (ADAs) through dose escalation and expansion.

  18. Immunogenicity [ Time Frame: up to 24 months ]
    Quantity of anti-drug antibodies (ADAs) through dose escalation and expansion.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05859464


Contacts
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Contact: Zai Lab 1218-001 Study Team 6502316519 ZL-1218-001@zailaboratory.com

Locations
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United States, California
Zai Lab Site 2005 Recruiting
Irvine, California, United States, 92618
United States, Michigan
Zai Lab Site 2007 Recruiting
Detroit, Michigan, United States, 48201
United States, New Jersey
Zai Lab Site 2001 Recruiting
Hackensack, New Jersey, United States, 07601
United States, New York
Zai Lab Site 2002 Recruiting
New York, New York, United States, 10029
United States, Washington
Zai Lab Site 2003 Recruiting
Spokane, Washington, United States, 99208
China
Zai Lab Site 1002 Recruiting
Hangzhou, China, 310009
Zai Lab Site 1001 Recruiting
Shanghai, China, 200123
Spain
Zai Lab Site 8004 Recruiting
Pozuelo De Alarcón, Madrid, Spain, 28223
Zai Lab Site 8005 Recruiting
Barcelona, Spain, 8023
Zai Lab Site 8001 Recruiting
Barcelona, Spain, 8035
Zai Lab Site 8003 Recruiting
Sevilla, Spain, 41009
Zai Lab Site 8002 Recruiting
Valencia, Spain, 46009
Zai Lab Site 8006 Recruiting
Valencia, Spain, 46010
Sponsors and Collaborators
Zai Lab (Hong Kong), Ltd.
Zai Biopharmaceutical (Shanghai) Co., Ltd.
Merck Sharp & Dohme LLC
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Responsible Party: Zai Lab (Hong Kong), Ltd.
ClinicalTrials.gov Identifier: NCT05859464    
Other Study ID Numbers: ZL-1218-001
KEYNOTE-F22, MK-3475-F22 ( Other Identifier: Merck Sharpe & Dohme, LLC )
First Posted: May 16, 2023    Key Record Dates
Last Update Posted: May 10, 2024
Last Verified: May 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action