An Open-label, Multicenter Study of ZL-1310 in Subjects With Small Cell Lung Cancer

Study Overview
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Brief Summary
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An Open-label, Multicenter Study of ZL-1310 to Evaluate the Safety, Tolerability, and Pharmacokinetics in Subjects with Small Cell Lung Cancer

Detailed Description
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This is an open-label, ascending, multiple-dose, phase 1 study of ZL-1310 administered intravenously (IV) every 3 weeks in subjects with relapsed/refractory (r/r) metastatic SCLC who have progressed after at least one platinum-based chemotherapy regimen.

Official Title
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An Open-label, Multicenter Study of ZL-1310 to Evaluate the Safety, Tolerability, and Pharmacokinetics in Subjects With Small Cell Lung Cancer

Conditions
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SCLC

Intervention / Treatment
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* Drug: ZL-1310


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Subjects must have histologically or cytologically confirmed metastatic or extensive-stage small cell lung cancer with documented disease progression during or following a platinum-based chemotherapy regimen. No more than 3 prior regimens in the r/r setting are allowed. Adult men and women ≥18 years of age. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Subjects must have at least one measurable target lesion as defined by RECIST v1.1 on CT, PET/CT, or MRI. Exclusion Criteria: Subjects with another known malignancy that is progressing or requires active treatment within the last 2 years. Exceptions: basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin with previously administered curative treatment, in situ cervical cancer, or other cancers that do not require systemic anti-cancer therapies and will not impact life expectancy. Symptomatic or untreated brain metastasis requiring concurrent treatment. Subjects with leptomeningeal metastasis. Treatment with any systemic anti-cancer treatment or other investigational products/ device within 3 weeks (exceptions: within 5 half-lives for short half-life drugs, or within 14 days for conventional chemotherapy if all treatment-related toxicities have resolved to baseline) before first dose of study treatment. Non-palliative radiotherapy within 2 weeks prior to first dose of study treatment or have had a history of radiation pneumonitis. Subjects who received radiation therapy to the lung that is >30 Gy within 6 months of the first dose of trial treatment are excluded Major surgery within 4 weeks of the first dose of study treatment. Prior exposure to DLL3-targeted therapy or hypersensitivity to any ingredient of the study treatment. Out of range lab value (as defined in protocol) within 10 days prior to the first dose of study treatment, Subjects with a diagnosis of immunodeficiency or receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 14 days or 5 half-lives before the first dose of study treatment, whichever is longer. Subjects have received a live or live-attenuated vaccine within 30 days of planned start of study therapy. Impaired cardiac function or clinically significant cardiac disease within the last 3 months before administration of the first dose of the study treatment Lung-specific intercurrent clinically significant illnesses and any autoimmune, connective tissue, or inflammatory disorders. Pregnant or nursing (lactating) women. Subjects who have been on concomitant strong CYP3A or CYP2D6 inhibitors within 14 days or 5 half-lives before the first study treatment, whichever is longer.

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: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation<br>Dose Escalation | Drug: ZL-1310<br>* Drug: ZL-1310<br>|
| Experimental: Dose Expansion: Arm 1<br>Dose level 1 established from escalation | Drug: ZL-1310<br>* Drug: ZL-1310<br>|
| Experimental: Dose Expansion: Arm 2<br>Dose level 2 established from escalation | Drug: ZL-1310<br>* Drug: ZL-1310<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) Number of subjects with Dose Limiting Toxicities (DLTs) | up to 24 months | 
| Incidence of Treatment Emergent Adverse-Events | Number of subjects with treatment-emergent adverse events (TEAEs) | up to 24 months | 
| Incidence of Serious Adverse Events | Number of subjects with serious adverse events (SAEs) | up to 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 | Time Frame: up to 24 months | 
| Overall Survival | Overall Survival (OS) | up to 24 months | 
| Pharmacokinetics (PK): Total Antibody | Total Antibody | up to 24 months | 
| Pharmacokinetics (PK): Unconjugated payloads | Unconjugated payloads | up to 24 months |