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

Primary Purpose

NSCLC

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
PM8002
Placebo
Carboplatin
Pemetrexed
Sponsored by
Biotheus Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for NSCLC

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Medical Ethics Committee of Guangdong Provincial People's HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

PM8002+Chemotherapy

Placebo+Chemotherapy

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.
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).

Secondary Outcome Measures

Overall survival (OS)
OS is the time from the date of randomization or first dosing date to death due to any cause.
ORR (only Part 2)
ORR is the proportion of subjects with CR or PR, based on RECIST v1.1.
Disease control rate (DCR)
DCR is defined as the proportion of subjects with CR, PR, or stable disease(SD) based on RECIST v1.1.
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.
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).
Pharmacokinetic (PK) parameters
The PK parameters include serum concentrations of PM8002 at different timepoints after study drug administration.
Anti-drug antibody(ADA)
To evaluate the incidence of ADA to PM8002
Treatment related adverse events (TRAEs)
The incidence and severity of TRAEs graded according to NCI-CTCAE v5.0
Correlation between PD-L1 expression and antitumor effect
To evaluate correlation between PD-L1 expression and antitumor effect

Full Information

First Posted
February 15, 2023
Last Updated
July 12, 2023
Sponsor
Biotheus Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05756972
Brief Title
A Study of PM8002 (Anti-PD-L1/VEGF) in Combination With Chemotherapy in Patients With NSCLC
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 26, 2023 (Actual)
Primary Completion Date
March 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biotheus Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.
Detailed 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
NSCLC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
374 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
PM8002+Chemotherapy
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo+Chemotherapy
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
PM8002
Intervention Description
IV infusion
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
IV infusion
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
IV infusion
Intervention Type
Drug
Intervention Name(s)
Pemetrexed
Intervention Description
IV infusion
Primary Outcome Measure Information:
Title
Objective response rate (Part 1)
Description
Objective response rate (ORR) is the proportion of subjects with complete response (CR) or partial response (PR), based on RECIST v1.1.
Time Frame
Up to approximately 2 years
Title
Progression free survival (Part 2)
Description
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).
Time Frame
Up to approximately 2 years
Secondary Outcome Measure Information:
Title
Overall survival (OS)
Description
OS is the time from the date of randomization or first dosing date to death due to any cause.
Time Frame
Up to approximately 2 years
Title
ORR (only Part 2)
Description
ORR is the proportion of subjects with CR or PR, based on RECIST v1.1.
Time Frame
Up to approximately 2 years
Title
Disease control rate (DCR)
Description
DCR is defined as the proportion of subjects with CR, PR, or stable disease(SD) based on RECIST v1.1.
Time Frame
Up to approximately 2 years
Title
Duration of response (DoR)
Description
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.
Time Frame
Up to approximately 2 years
Title
Time to response (TTR)
Description
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).
Time Frame
Up to approximately 2 years
Title
Pharmacokinetic (PK) parameters
Description
The PK parameters include serum concentrations of PM8002 at different timepoints after study drug administration.
Time Frame
Up to 30 days after last treatment
Title
Anti-drug antibody(ADA)
Description
To evaluate the incidence of ADA to PM8002
Time Frame
Up to 30 days after last treatment
Title
Treatment related adverse events (TRAEs)
Description
The incidence and severity of TRAEs graded according to NCI-CTCAE v5.0
Time Frame
Up to 30 days after last treatment
Title
Correlation between PD-L1 expression and antitumor effect
Description
To evaluate correlation between PD-L1 expression and antitumor effect
Time Frame
Up to approximately 2 years
Other Pre-specified Outcome Measures:
Title
Population PK analysis
Description
To assess the Exposure-Response of PM8002 by means of population PK (popPK) analysis
Time Frame
Up to 30 days after last treatment
Title
Correlation between PM8002 exposure, immunogenicity and efficacy
Description
To evaluate correlation between PM8002 exposure, immunogenicity and efficacy
Time Frame
Up to approximately 2 years
Title
Correlation between PM8002 exposure, immunogenicity and safety
Description
To evaluate correlation between PM8002 exposure, immunogenicity and safety
Time Frame
Up to 30 days after last treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhang Jie
Phone
+86 021 32120207
Email
zhang.jie@biotheus.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wu Yilong, PhD
Organizational Affiliation
Guangdong Provincial People's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical Ethics Committee of Guangdong Provincial People's Hospital
City
Guangzhou
State/Province
Guangdonng
ZIP/Postal Code
519041
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wu Yilong

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.

Learn more about this trial

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

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