A Phase 1 Study of ZL-1218 in Subjects With Advanced Solid Tumors
- Conditions
- Malignant Solid Tumor
- Interventions
- Drug: ZL-1218Drug: Pembrolizumab
- Registration Number
- NCT05859464
- Lead Sponsor
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 60
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 2: Cohort Expansion; Prior CPI Therapy ZL-1218 Drug: ZL-1218 ZL-1218 recommended dose Drug: Pembrolizumab (KEYTRUDA®) Combination treatment with ZL-1218 Part 1: Dose Escalation; ZL-1218 ZL-1218 Drug: ZL-1218 ZL-1218 dose escalation Part 1: Dose Escalation; ZL-1218 in combination with Pembrolizumab ZL-1218 Drug: ZL-1218 ZL-1218 dose escalation Drug: Pembrolizumab (KEYTRUDA®) Combination treatment with ZL-1218 Part 2: Cohort Expansion; CPI therapy Naive ZL-1218 Drug: ZL-1218 ZL-1218 recommended dose Drug: Pembrolizumab (KEYTRUDA®) Combination treatment with ZL-1218 Part 1: Dose Escalation; ZL-1218 in combination with Pembrolizumab Pembrolizumab Drug: ZL-1218 ZL-1218 dose escalation Drug: Pembrolizumab (KEYTRUDA®) Combination treatment with ZL-1218 Part 2: Cohort Expansion; Prior CPI Therapy Pembrolizumab Drug: ZL-1218 ZL-1218 recommended dose Drug: Pembrolizumab (KEYTRUDA®) Combination treatment with ZL-1218 Part 2: Cohort Expansion; CPI therapy Naive Pembrolizumab Drug: ZL-1218 ZL-1218 recommended dose Drug: Pembrolizumab (KEYTRUDA®) Combination treatment with ZL-1218
- Primary Outcome Measures
Name Time Method Incidence of Dose Limiting Toxicities Approximately 24 months Number of subjects with dose limiting toxicities (DLTs) through dose escalation only.
Incidence of Treatment Emergent Adverse Events Approximately 24 months Number of subjects with treatment-emergent adverse effects through dose escalation and expansion.
ORR per RECIST 1.1 up to 24 months Objective Response Rate (ORR) per RECIST 1.1 through dose expansion only.
ORR per iRECIST up to 24 months Objective Response Rate per iRECIST through dose expansion only.
Clinically Significant changes in safety assessments Approximately 24 months Changes in safety assessment parameters (e.g., vital signs, electrocardiograms \[ECGs\], and clinical laboratory results) through dose escalation and expansion.
Incidence of Serious adverse events Approximately 24 months Number of subjects with Serious Adverse Events through dose escalation and expansion.
- Secondary Outcome Measures
Name Time Method Pharmacokinetics (PK): AUC up to 24 months Area under curve (AUC) through dose escalation and expansion.
ORR per iRECIST up to 24 months Objective Response Rate (ORR) per iRECIST through dose escalation only.
PFS per iRECIST up to 24 months Progression-Free Survival (PFS) per iRECIST through dose escalation and expansion.
Duration of Response per RECIST 1.1 up to 24 months Duration of Response per RECIST 1.1 through dose escalation and expansion.
PFS per RECIST 1.1 up to 24 months Progression-Free Survival (PFS) per RECIST 1.1 through dose escalation and expansion.
DCR per iRECIST up to 24 months Disease Control Rate (DCR) per iRECIST through dose escalation and expansion.
Duration of Response per iRECIST up to 24 months Duration of Response per iRECIST through dose escalation and expansion.
Pharmacokinetics (PK): Ctrough up to 24 months Ctrough through dose escalation and expansion.
Pharmacokinetics (PK): Vss up to 24 months Volume of distribution as steady state (Vss) through dose escalation and expansion.
ORR per RECIST 1.1 up to 24 months Objective Response Rate (ORR) per RECIST 1.1 through dose escalation only.
DCR per RECIST 1.1 up to 24 months Disease Control Rate (DCR) per RECIST 1.1 through dose escalation and expansion.
Overall Survival up to 24 months Overall Survival (OS) through dose escalation and expansion.
Pharmacokinetics (PK): CL up to 24 months Clearance (CL) through dose escalation and expansion.
Pharmacokinetics (PK): t1/2 up to 24 months Half-life (t1/2) through dose escalation and expansion.
Pharmacokinetics (PK): Cmax up to 24 months Maximum serum concentration (CMax) through dose escalation and expansion.
Pharmacokinetics (PK): Tmax up to 24 months Time to reach Cmax (Tmax) through dose escalation and expansion.
Immunogenicity up to 24 months Quantity of anti-drug antibodies (ADAs) through dose escalation and expansion.
Trial Locations
- Locations (15)
Zai Lab Site 2005
🇺🇸Irvine, California, United States
Zai Lab Site 2007
🇺🇸Detroit, Michigan, United States
Zai Lab Site 2001
🇺🇸Hackensack, New Jersey, United States
Zai Lab Site 2002
🇺🇸New York, New York, United States
Zai Lab Site 2003
🇺🇸Spokane, Washington, United States
Zai Lab Site 1002
🇨🇳Hangzhou, China
Zai Lab Site 1001
🇨🇳Shanghai, China
Zai Lab Site 8004
🇪🇸Pozuelo De Alarcón, Madrid, Spain
Zai Lab Site 8005
🇪🇸Barcelona, Spain
Zai Lab Site 8001
🇪🇸Barcelona, Spain
Zai Lab Site 8007
🇪🇸Madrid, Spain
Zai Lab Site 8008
🇪🇸Madrid, Spain
Zai Lab Site 8003
🇪🇸Sevilla, Spain
Zai Lab Site 8002
🇪🇸Valencia, Spain
Zai Lab Site 8006
🇪🇸Valencia, Spain
Related News
Advancing clinical-basic-clinical research: exploring novel immunotargets for ovarian cancer
- Prev
- 1
- Next