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

Malignant Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05859464
• Other study ID #: ZL-1218-001
• Secondary ID: KEYNOTE-F22, MK-
• Status: Recruiting
• Phase: Phase 1
• Start date: July 24, 2023
• Est. completion date: November 2025

Study information

• Verified date: May 2024
• Source: Zai Lab (Hong Kong), Ltd.
• Contact: Zai Lab 1218-001 Study Team
• Phone: 6502316519
• Email: ZL-1218-001[@]zailaboratory.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: November 2025
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Malignant Solid Tumor
• Neoplasms

Intervention

Drug:
• ZL-1218
ZL-1218 dose escalation
• Pembrolizumab
Combination treatment with ZL-1218

Locations

Country	Name	City	State
China	Zai Lab Site 1002	Hangzhou
China	Zai Lab Site 1001	Shanghai
Spain	Zai Lab Site 8001	Barcelona
Spain	Zai Lab Site 8005	Barcelona
Spain	Zai Lab Site 8004	Pozuelo De Alarcón	Madrid
Spain	Zai Lab Site 8003	Sevilla
Spain	Zai Lab Site 8002	Valencia
Spain	Zai Lab Site 8006	Valencia
United States	Zai Lab Site 2007	Detroit	Michigan
United States	Zai Lab Site 2001	Hackensack	New Jersey
United States	Zai Lab Site 2005	Irvine	California
United States	Zai Lab Site 2002	New York	New York
United States	Zai Lab Site 2003	Spokane	Washington

Sponsors (3)

Lead Sponsor	Collaborator
Zai Lab (Hong Kong), Ltd.	Merck Sharp & Dohme LLC, Zai Biopharmaceutical (Shanghai) Co., Ltd.

Countries where clinical trial is conducted

United States,  China,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Dose Limiting Toxicities	Number of subjects with dose limiting toxicities (DLTs) through dose escalation only.	Approximately 24 months
Primary	Incidence of Treatment Emergent Adverse Events	Number of subjects with treatment-emergent adverse effects through dose escalation and expansion.	Approximately 24 months
Primary	Incidence of Serious adverse events	Number of subjects with Serious Adverse Events through dose escalation and expansion.	Approximately 24 months
Primary	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
Primary	ORR per RECIST 1.1	Objective Response Rate (ORR) per RECIST 1.1 through dose expansion only.	up to 24 months
Primary	ORR per iRECIST	Objective Response Rate per iRECIST through dose expansion only.	up to 24 months
Secondary	ORR per RECIST 1.1	Objective Response Rate (ORR) per RECIST 1.1 through dose escalation only.	up to 24 months
Secondary	ORR per iRECIST	Objective Response Rate (ORR) per iRECIST through dose escalation only.	up to 24 months
Secondary	Duration of Response per RECIST 1.1	Duration of Response per RECIST 1.1 through dose escalation and expansion.	up to 24 months
Secondary	Duration of Response per iRECIST	Duration of Response per iRECIST through dose escalation and expansion.	up to 24 months
Secondary	PFS per RECIST 1.1	Progression-Free Survival (PFS) per RECIST 1.1 through dose escalation and expansion.	up to 24 months
Secondary	PFS per iRECIST	Progression-Free Survival (PFS) per iRECIST through dose escalation and expansion.	up to 24 months
Secondary	DCR per RECIST 1.1	Disease Control Rate (DCR) per RECIST 1.1 through dose escalation and expansion.	up to 24 months
Secondary	DCR per iRECIST	Disease Control Rate (DCR) per iRECIST through dose escalation and expansion.	up to 24 months
Secondary	Overall Survival	Overall Survival (OS) through dose escalation and expansion.	up to 24 months
Secondary	Pharmacokinetics (PK): AUC	Area under curve (AUC) through dose escalation and expansion.	up to 24 months
Secondary	Pharmacokinetics (PK): Cmax	Maximum serum concentration (CMax) through dose escalation and expansion.	up to 24 months
Secondary	Pharmacokinetics (PK): Tmax	Time to reach Cmax (Tmax) through dose escalation and expansion.	up to 24 months
Secondary	Pharmacokinetics (PK): Ctrough	Ctrough through dose escalation and expansion.	up to 24 months
Secondary	Pharmacokinetics (PK): Vss	Volume of distribution as steady state (Vss) through dose escalation and expansion.	up to 24 months
Secondary	Pharmacokinetics (PK): CL	Clearance (CL) through dose escalation and expansion.	up to 24 months
Secondary	Pharmacokinetics (PK): t1/2	Half-life (t1/2) through dose escalation and expansion.	up to 24 months
Secondary	Immunogenicity	Incidence of anti-drug antibodies (ADAs) through dose escalation and expansion.	up to 24 months
Secondary	Immunogenicity	Quantity of anti-drug antibodies (ADAs) through dose escalation and expansion.	up to 24 months