Malignant Solid Tumor
Conditions
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.
Interventions
DRUGZL-1218
ZL-1218 dose escalation
DRUGPembrolizumab
Combination treatment with ZL-1218
Sponsors
Zai Biopharmaceutical (Shanghai) Co., Ltd.
Merck Sharp & Dohme LLC
Zai Lab (Hong Kong), Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Incidence of Serious adverse events | Approximately 24 months | Number of subjects with Serious Adverse Events through dose escalation and expansion. |
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| DCR per RECIST 1.1 | up to 24 months | Disease Control Rate (DCR) 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. |
| Overall Survival | up to 24 months | Overall Survival (OS) through dose escalation and expansion. |
| Pharmacokinetics (PK): AUC | up to 24 months | Area under curve (AUC) through dose escalation and expansion. |
| Pharmacokinetics (PK): Cmax | up to 24 months | Maximum serum concentration (CMax) 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. |
| 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. |
| 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. |
| Immunogenicity | up to 24 months | Incidence of anti-drug antibodies (ADAs) through dose escalation and expansion. |
| Pharmacokinetics (PK): Tmax | up to 24 months | Time to reach Cmax (Tmax) through dose escalation and expansion. |
| ORR per iRECIST | up to 24 months | Objective Response Rate (ORR) per iRECIST through dose escalation only. |
| Duration of Response per RECIST 1.1 | up to 24 months | Duration of Response per RECIST 1.1 through dose escalation and expansion. |
| Duration of Response per iRECIST | up to 24 months | Duration of Response per iRECIST 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. |
| PFS per iRECIST | up to 24 months | Progression-Free Survival (PFS) per iRECIST through dose escalation and expansion. |
Countries
China, Spain, United States
Outcome results
None listed