A Study of PM8002 (Anti-PD-L1/VEGF) in Combination With Chemotherapy in Patients With ES-SCLC

Study Overview
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Brief Summary
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PM8002 is a bispecific antibody targeting PD-L1 and VEGF. This study to evaluate the efficacy and safety of PM8002 in combination with etoposide and platinum in first-line treatment of extensive-stage small cell lung cancer

Detailed Description
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The study is divided into two parts. The first part is single-arm study, with a planned enrollment of at least 59 subjects. The second part is randomized, double-blind study, this study plans to enroll 386 subjects, who will be randomized in a 1:1 ratio to an experimental group of PM8002 in combination with chemotherapy (etoposide and platinum) and a control group of Atezolizumab with chemotherapy (etoposide and platinum).

Official Title
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A Phase II/III Clinical Trial to Evaluate the Efficacy and Safety of PM8002 in Combination With Etoposide and Platinum in First-line Treatment of Extensive-Stage Small Cell Lung Cancer

Conditions
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SCLC

Intervention / Treatment
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* Drug: PM8002
* Drug: Platinum
* Drug: Atezolizumab
* Drug: Etoposide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent form before any trial-related processes; Age ≥18 years; Histologically or cytologically confirmed ES-SCLC; No prior systemic therapy for ES-SCLC; Have adequate organ function; The Eastern Cancer Cooperative Group (ECOG) performance score of 0 or 1; Life expectancy of ≥12 weeks; Had at least one measurable tumor lesion according to RECIST v1.1. Exclusion Criteria: Histologically or cytologically confirmed mixed SCLC; History of severe allergic disease, severe drug allergy or have known allergy to any component of the study drugs; The toxicity of previous anti-tumor therapy has not been alleviated； Have received anti-platelet therapy within 10 days prior to the first dose of the study drugs; Evidence and history of severe bleeding tendency; History of severe cardiovascular diseases within 6 months; Current presence of uncontrolled pleural, pericardial, and peritoneal effusions; History of allogeneic hematopoietic stem cell transplantation or allogeneic organ transplantation; History of alcohol abuse, psychotropic substance abuse or drug abuse; Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome; Pregnant or lactating women; Other conditions considered unsuitable for this study by the investigator.

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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PM8002+Etoposide＋platinum<br>Subjects will be administered with PM8002 plus Etoposide and platinum via intravenously (IV) Q3W for 4 cycles, followed by PM8002 until progression or for a maximum of 2 years. | Drug: PM8002<br>* IV infusion<br>Drug: Platinum<br>* IV infusion<br>Drug: Etoposide<br>* IV infusion<br>|
| Active Comparator: Atezolizumab+Etoposide＋platinum<br>Subjects will be administered with Atezolizumab plus Etoposide and platinum via intravenously (IV) Q3W for 4 cycles, followed by Atezolizumab until progression or for a maximum of 2 years. | Drug: Platinum<br>* IV infusion<br>Drug: Atezolizumab<br>* IV infusion<br>Drug: Etoposide<br>* IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (Part 1) | Objective response rate (ORR) is the proportion of subjects with complete response (CR) or partial response (PR), based on RECIST v1.1. | Up to approximately 2 years | 
| Overall survival (Part 2) | Overall survival (OS) is the time from the date of randomization or first dosing date to death due to any cause. | Up to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (Only for Part 1) | OS is the time from the date of randomization or first dosing date to death due to any cause. | Up to approximately 2 years | 
| Progression free survival (PFS) | Progression free survival (PFS) is defined as the time from the start of treatment until the first documentation of disease progression or death due to any cause, whichever occurs first (based on RECIST v1.1). | Up to approximately 2 years | 
| Disease control rate (DCR) | DCR is defined as the proportion of subjects with CR, PR, or stable disease (SD) based on RECIST v1.1. | Up to approximately 2 years | 
| Duration of response (DOR) | DOR is defined as the duration from the first documentation of objective response to the first documented disease progression (based on RECIST v1.1) or death due to any cause, whichever occurs first. | Up to approximately 2 years | 
| Time to response (TTR) | TTR is defined as the time from the start of the treatment to the first objective tumor response observed for patients who achieve CR or PR (based on RECIST v1.1). | Up to approximately 2 years | 
| Objective response rate (ORR) (Only for Part 2) | Objective response rate (ORR) is the proportion of subjects with complete response (CR) or partial response (PR), based on RECIST v1.1. | Up to approximately 2 years | 
| Pharmacokinetic (PK) parameters | The PK parameters including serum concentrations of PM8002 at different time points after study drug administration. | Up to 30 days after last treatment | 
| Anti-drug antibody (ADA) | To evaluate the incidence of ADA to PM8002. | Up to 30 days after last treatment | 
| Treatment related adverse events (TRAEs) | The incidence and severity of TRAEs graded according to NCI-CTCAE v5.0 | Up to 30 days after last treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ES-SCLC