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

Study Overview
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Brief Summary
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PM8002 is a bispecific antibody targeting PD-L1 and VEGF. This is a phase II/III study to evaluate the efficacy and safety of PM8002 in combination with pemetrexed and carboplatin in patients with EGFR-mutant locally advanced or metastatic non-squamous NSCLC who have failed to EGFR-TKI treatment.

Detailed Description
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The study is divided into two parts. The first part is a phase II, single-arm study, which is planned to enroll 60 subjects. The second part is a phase III randomized, double-blind, placebo-controlled study. The study plans to enroll 314 subjects, who will be randomized in a 1:1 ratio to an experimental group of PM8002 in combination with chemotherapy (pemetrexed and carboplatin) and a control group of chemotherapy (pemetrexed and carboplatin).

Official Title
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A Phase II/III Clinical Trial to Evaluate the Efficacy and Safety of PM8002(Anti-PD-L1/VEGF) in Combination With Chemotherapy in Patients With EGFR-mutant Advanced Non-squamous NSCLC Who Have Failed to EGFR-TKI Treatment

Conditions
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NSCLC

Intervention / Treatment
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* Drug: PM8002
* Drug: Placebo
* Drug: Carboplatin
* Drug: Pemetrexed


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 male or female. Have a histologically or cytologically confirmed stage IIIB/IIIC NSCLC that is unresectable and not fit for radical concurrent chemoradiotherapy, or metastatic non-squamous NSCLC (IV). with EGFR mutation confirmed by tumor histology or cytology or hematology prior to EGFR-TKI treatment. EGFR-TKI resistance, confirmed by RECIST v1.1. have adequate organ function. The investigator confirms at least one measurable lesion according to RECIST v1.1. A measurable lesion located in the field of previous radiation therapy or after local treatment may be selected as a target lesion if progression is confirmed. The Eastern Cancer Cooperative Group (ECOG) performance score of 0 or 1. Exclusion Criteria: Squamous cell > 10%. If small cell types are present, the subject is not eligible for inclusion. Have other driving gene mutations that can obtain effective treatment. Have previously received systemic anti-tumor treatment other than EGFR-TKI for advanced non-squamous NSCLC. Have received systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to the first dose of study drugs. Have received EGFR-TKI treatment, within 14 days prior to the first dose of study drugs Anticoagulant or thrombolytic agent within 10 days prior to the first dose of study drugs. Evidence and history of severe bleeding tendency or coagulation dysfunction. The toxicity of previous anti-tumor therapy has not been alleviated. Symptomatic central nervous system metastases (CNS) metastasis and/or cancerous meningitis. Have suffered from the second primary active malignant tumor in the past 5 years.

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+Chemotherapy<br>Subjects will be administered with PM8002 plus pemetrexed and carboplatin via intravenously (IV) Q3W for 4 cycles, followed by PM8002 and pemetrexed until progression or for a maximum of 2 years. | Drug: PM8002<br>* IV infusion<br>Drug: Carboplatin<br>* IV infusion<br>Drug: Pemetrexed<br>* IV infusion<br>|
| Experimental: Placebo+Chemotherapy<br>Subjects will be administered with placebo plus pemetrexed and carboplatin via intravenously (IV) Q3W for 4 cycles, followed by placebo and pemetrexed until progression or for a maximum of 2 years. | Drug: Placebo<br>* IV infusion<br>Drug: Carboplatin<br>* IV infusion<br>Drug: Pemetrexed<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 | 
| Progression free survival (Part 2) | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | OS is the time from the date of randomization or first dosing date to death due to any cause. | Up to approximately 2 years | 
| ORR (only Part 2) | ORR is the proportion of subjects with CR or PR, 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 | 
| Pharmacokinetic (PK) parameters | The PK parameters include serum concentrations of PM8002 at different timepoints 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 | 
| Correlation between PD-L1 expression and antitumor effect | To evaluate correlation between PD-L1 expression and antitumor effect | Up to approximately 2 years |