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

A Phase II 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

PM8002 is a bispecific antibody targeting PD-L1 and VEGF. This is a phase II 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.

Study Overview

• Status: Active, not recruiting
• Conditions: NSCLC
• Intervention / Treatment: Drug: Carboplatin; Drug: Pemetrexed; Drug: PM8002

Detailed Description

This study is a phase II, single-arm study, 64 participants were enrolled as of 6 Feb 2024, and recruitment was completed.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdonng
    • Guangzhou, Guangdonng, China, 519041
      • Medical Ethics Committee of Guangdong Provincial People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed informed consent form before any trial-related processes.
2. Age ≥ 18 years male or female.
3. 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).
4. with EGFR mutation confirmed by tumor histology or cytology or hematology prior to EGFR-TKI treatment.
5. EGFR-TKI resistance, confirmed by RECIST v1.1.
6. have adequate organ function.
7. 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.
8. The Eastern Cancer Cooperative Group (ECOG) performance score of 0 or 1.

Exclusion Criteria:

1. Squamous cell > 10%. If small cell types are present, the subject is not eligible for inclusion.
2. Have other driving gene mutations that can obtain effective treatment.
3. Have previously received systemic anti-tumor treatment other than EGFR-TKI for advanced non-squamous NSCLC.
4. Have received systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to the first dose of study drugs.
5. Have received EGFR-TKI treatment, within 14 days prior to the first dose of study drugs
6. Anticoagulant or thrombolytic agent within 10 days prior to the first dose of study drugs.
7. Evidence and history of severe bleeding tendency or coagulation dysfunction.
8. The toxicity of previous anti-tumor therapy has not been alleviated.
9. Symptomatic central nervous system metastases (CNS) metastasis and/or cancerous meningitis.
10. Have suffered from the second primary active malignant tumor in the past 5 years.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PM8002+Chemotherapy; 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: Carboplatin; IV infusion; Drug: Pemetrexed; IV infusion; Drug: PM8002; IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	Objective response rate is the proportion of subjects with complete response (CR) or partial response (PR), 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
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
Progression free survival (PFS)	Progression free survival 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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Population PK analysis	To assess the Exposure-Response of PM8002 by means of population PK (popPK) analysis	Up to 30 days after last treatment
Correlation between PM8002 exposure, immunogenicity and efficacy	To evaluate correlation between PM8002 exposure, immunogenicity and efficacy	Up to approximately 2 years
Correlation between PM8002 exposure, immunogenicity and safety	To evaluate correlation between PM8002 exposure, immunogenicity and safety	Up to 30 days after last treatment

Collaborators and Investigators

• Sponsor: Biotheus Inc.
• Investigators: Principal Investigator: Wu Yilong, PhD, Guangdong Provincial People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2023
• Primary Completion (Actual): September 13, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: February 15, 2023
• First Submitted That Met QC Criteria: February 23, 2023
• First Posted (Actual): March 7, 2023

Study Record Updates

• Last Update Posted (Actual): April 3, 2025
• Last Update Submitted That Met QC Criteria: March 31, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Pemetrexed; Carboplatin
• Other Study ID Numbers: PM8002-BC010C-NSCLC-R

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data will be published or presented for publications (poster, abstract, articles or papers) or any presentations.
• IPD Sharing Time Frame: After the trial completed
• IPD Sharing Access Criteria: NCI is committed to sharing data in accordance with NIH policy.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No