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

NSCLC Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05756972
• Other study ID #: PM8002-BC010C-NSCLC-R
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: June 26, 2023
• Est. completion date: December 2025

Study information

• Verified date: July 2023
• Source: Biotheus Inc.
• Contact: Zhang Jie
• Phone: +86 021 32120207
• Email: zhang.jie[@]biotheus.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 374
• Est. completion date: December 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• NSCLC

Intervention

Drug:
• PM8002
IV infusion
• Placebo
IV infusion
• Carboplatin
IV infusion
• Pemetrexed
IV infusion

Locations

Country	Name	City	State
China	Medical Ethics Committee of Guangdong Provincial People's Hospital	Guangzhou	Guangdonng

Sponsors (1)

Lead Sponsor	Collaborator
Biotheus Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Population PK analysis	To assess the Exposure-Response of PM8002 by means of population PK (popPK) analysis	Up to 30 days after last treatment
Other	Correlation between PM8002 exposure, immunogenicity and efficacy	To evaluate correlation between PM8002 exposure, immunogenicity and efficacy	Up to approximately 2 years
Other	Correlation between PM8002 exposure, immunogenicity and safety	To evaluate correlation between PM8002 exposure, immunogenicity and safety	Up to 30 days after last treatment
Primary	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
Primary	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	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
Secondary	ORR (only Part 2)	ORR is the proportion of subjects with CR or PR, based on RECIST v1.1.	Up to approximately 2 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Anti-drug antibody(ADA)	To evaluate the incidence of ADA to PM8002	Up to 30 days after last treatment
Secondary	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
Secondary	Correlation between PD-L1 expression and antitumor effect	To evaluate correlation between PD-L1 expression and antitumor effect	Up to approximately 2 years