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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Malignant Solid Tumor

Intervention / Treatment
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* Drug: ZL-1218
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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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. 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. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ZL-1218<br> | Drug: ZL-1218<br>* ZL-1218 dose escalation<br>|
| Experimental: ZL-1218 in combination with Pembrolizumab<br> | Drug: ZL-1218<br>* ZL-1218 dose escalation<br>Drug: Pembrolizumab<br>* Combination treatment with ZL-1218<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Dose Limiting Toxicities | Number of subjects with dose limiting toxicities (DLTs) | Approximately 24 months | 
| Incidence of Treatment Emergent Adverse Events | Number of subjects with treatment-emergent adverse effects | Approximately 24 months | 
| Incidence of Serious adverse events | Number of subjects with Serious Adverse Events | Approximately 24 months | 
| Clinically Significant changes in safety assessments | Changes in safety assessment parameters (e.g., vital signs, electrocardiograms [ECGs], and clinical laboratory results) . | Approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR per RECIST 1.1 | Objective Response Rate (ORR) per RECIST 1.1 | up to 24 months | 
| ORR per iRECIST | Objective Response Rate (ORR) per iRECIST | up to 24 months | 
| Duration of Response per RECIST 1.1 | Duration of Response per RECIST 1.1 | up to 24 months | 
| Duration of Response per iRECIST | Duration of Response per iRECIST | up to 24 months | 
| PFS per RECIST 1.1 | Progression-Free Survival (PFS) per RECIST 1.1 | up to 24 months | 
| PFS per iRECIST | Progression-Free Survival (PFS) per iRECIST | up to 24 months | 
| DCR per RECIST 1.1 | Disease Control Rate (DCR) per RECIST 1.1 | up to 24 months | 
| DCR per iRECIST | Disease Control Rate (DCR) per iRECIST | up to 24 months | 
| Overall Survival | Overall Survival (OS) | up to 24 months | 
| Pharmacokinetics (PK): AUC | Area under curve (AUC) | up to 24 months | 
| Pharmacokinetics (PK): Cmax | Maximum serum concentration (CMax) | up to 24 months | 
| Pharmacokinetics (PK): Tmax | Time to reach Cmax (Tmax) | up to 24 months | 
| Pharmacokinetics (PK): Ctrough | Ctrough | up to 24 months | 
| Pharmacokinetics (PK): Vss | Volume of distribution as steady state (Vss) | up to 24 months | 
| Pharmacokinetics (PK): CL | Clearance (CL) | up to 24 months | 
| Pharmacokinetics (PK): t1/2 | Half-life (t1/2) | up to 24 months | 
| Immunogenicity | Incidence of anti-drug antibodies (ADAs) | up to 24 months | 
| Immunogenicity | Quantity of anti-drug antibodies (ADAs) | up to 24 months |