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

NCT05859464 | Terminated Phase 1 FDA Drug

• 2 other identifiers: ZL-1218-001KEYNOTE-F22, MK-3475-F22
• Study Type: interventional
• Target: 34
• Locations: 3 countries
• Sites: 15

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.

Conditions

Malignant Solid Tumor

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (18)

• ORR per RECIST 1.1

  up to 24 months

• ORR per iRECIST

  up to 24 months

• Duration of Response per RECIST 1.1

  up to 24 months

• Duration of Response per iRECIST

  up to 24 months

• PFS per RECIST 1.1

  up to 24 months

Study Arms (4)

Part 1: Dose Escalation; ZL-1218

EXPERIMENTAL

Drug: ZL-1218 ZL-1218 dose escalation

Drug: ZL-1218

Part 1: Dose Escalation; ZL-1218 in combination with Pembrolizumab

EXPERIMENTAL

Drug: ZL-1218 ZL-1218 dose escalation Drug: Pembrolizumab (KEYTRUDA®) Combination treatment with ZL-1218

Drug: ZL-1218; Drug: Pembrolizumab

Part 2: Cohort Expansion; Prior CPI Therapy

EXPERIMENTAL

Drug: ZL-1218 ZL-1218 recommended dose Drug: Pembrolizumab (KEYTRUDA®) Combination treatment with ZL-1218

Drug: ZL-1218; Drug: Pembrolizumab

Part 2: Cohort Expansion; CPI therapy Naive

EXPERIMENTAL

Drug: ZL-1218 ZL-1218 recommended dose Drug: Pembrolizumab (KEYTRUDA®) Combination treatment with ZL-1218

Drug: ZL-1218; Drug: Pembrolizumab

Interventions

ZL-1218 DRUG

ZL-1218 dose escalation

Part 1: Dose Escalation; ZL-1218; Part 1: Dose Escalation; ZL-1218 in combination with Pembrolizumab; Part 2: Cohort Expansion; CPI therapy Naive; Part 2: Cohort Expansion; Prior CPI Therapy

Pembrolizumab DRUG

Combination treatment with ZL-1218

Part 1: Dose Escalation; ZL-1218 in combination with Pembrolizumab; Part 2: Cohort Expansion; CPI therapy Naive; Part 2: Cohort Expansion; Prior CPI Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Zai Lab (Hong Kong), Ltd.: lead
• Zai Biopharmaceutical (Shanghai) Co., Ltd.: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (15)

Zai Lab Site 2005

Irvine, California, 92618, United States

Location

Zai Lab Site 2007

Detroit, Michigan, 48201, United States

Location

Zai Lab Site 2001

Hackensack, New Jersey, 07601, United States

Location

Zai Lab Site 2002

New York, New York, 10029, United States

Location

Zai Lab Site 2003

Spokane, Washington, 99208, United States

Location

Zai Lab Site 1002

Hangzhou, 310009, China

Location

Zai Lab Site 1001

Shanghai, 200123, China

Location

Zai Lab Site 8005

Barcelona, Barcelona, 8023, Spain

Location

Zai Lab Site 8001

Barcelona, Barcelona, 8035, Spain

Location

Zai Lab Site 8007

Madrid, Madrid, 28040, Spain

Location

Zai Lab Site 8008

Madrid, Madrid, 28050, Spain

Location

Zai Lab Site 8004

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Zai Lab Site 8003

Seville, Sevilla, 41009, Spain

Location

Zai Lab Site 8002

Valencia, Valencia, 46009, Spain

Location

Zai Lab Site 8006

Valencia, Valencia, 46010, Spain

Location

MeSH Terms

Interventions

pembrolizumab

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2023
• First Posted: May 16, 2023
• Study Start: July 24, 2023
• Primary Completion: August 28, 2025
• Study Completion: August 28, 2025
• Last Updated: October 20, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

ES (8); CN (2); US (5)