Phase III Study of Envafolimab Versus Placebo Plus Chemotherapy in Resectable Stage III NSCLC

A Randomized, Controlled, Double-blind, Multicenter Phase III Clinical Study of Envafolimab Plus Platinum-based Doublet Chemotherapy Versus Placebo Plus Platinum-based Doublet Chemotherapy in Patients With Non-small Cell Lung Cancer

This is a randomized, controlled, double-blind, multicenter Phase 3 clinical study to assess the efficacy and safety of envafolimab plus platinum-based doublet chemotherapy versus placebo plus platinum-based doublet chemotherapy as neoadjuvant/adjuvant therapy in subjects with resectable stage IIIA and IIIB (N2) NSCLC. Primary study endpoints are MPR rate assessed by BIPR and EFS assessed by BIRC.

Study Overview

• Status: Recruiting
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Envalfolimab subcutaneously injected+Platinum-based doublet chemotherapy intravenous injection; Drug: placebo subcutaneously injected +Platinum-based doublet chemotherapy intravenous injection

Detailed Description

A total of approximately 390 participants are planned to be enrolled in this study. After being screened and qualified, the subjects will be randomly assigned to receive Envalfolimab or placebo plus platinum-based doublet chemotherapy in 1:1 ratio for a total of 3-4 cycles of neoadjuvant therapy (determined by the investigator), the feasibility of surgery is evaluated by the investigator within 4-6 weeks after the end of neoadjuvant therapy and surgery will be performed. Envafolimab (experimental group) or placebo (control group) will be administered after surgery. After completion of treatment, subjects will enter a follow-up phase, including safety follow-up, tumor disease follow-up, and survival follow-up.All randomized subjects in this study are required to receive tumor imaging evaluation as scheduled and get continuous safety assessment during the srceening and treatment period.

• Study Type: Interventional
• Enrollment (Estimated): 390
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Changli Wang; Phone Number: 0086-22-2340123; Email: Wangchangli@tjmuch.com

Study Locations

• China
  • Tianjin
    • Tianjing, Tianjin, China, 300060
      • Recruiting
      • Tianjin Cancer Hospital
      • Contact: Changli Wang; Phone Number: 0086-22-2340123; Email: Wangchangli@tjmuch.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Volunteer to participate and sign the informed consent form.
2. Age ≥ 18 years old, regardless of gender.
3. Histological and/or cytological diagnosis of resectable stage IIIA-IIIB (N2) NSCLC.
4. Measurable lesions based on the response evaluation criteria in solid tumors version 1.1（RECIST 1.1）.
5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
6. Subjects should provide tumor tissue for detection of PD-L1 expression level.
7. Sufficient organ and bone marrow function.
8. Expected survival ≥6 months.
9. The surgeon assessed that total lung function is able to withstand the proposed pneumonectomy procedure.

Exclusion Criteria:

1. Tumor histologically or cytologically confirmed or combined with neuroendocrine carcinoma components, or sarcomatous/sarcomatoid lesions, or adenosquamous carcinoma, or special pathological types.
2. Previous treatment with another drug that targets T cell receptors (e.g. CTLA-4, OX-40, etc.);
3. Participants with known EGFR mutation or ALK translocation, and non-squamous cell carcinoma subjects need to identify EGFR and ALK mutation status;
4. Upper lung sulcus tumor or locally advanced unresectable or metastatic disease.
5. Previous anti-tumor therapy for the disease.
6. Subjects with known or suspected interstitial pneumonia.Radiation pneumonia or other moderate to severe lung disease that may interfere with the detection or management of drug-related pulmonary toxicity and seriously affect respiratory function.
7. Any serious active infection.
8. With uncontrolled or significant cardiovascular and cerebrovascular disease.
9. Active autoimmune disease requiring systemic treatment.
10. Immunosuppressant or systemic hormone therapy (dose >10 mg/ day prednisone or other therapeutic hormone) for immunosuppression within 14 days prior to randomization.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Envalfolimab plus platinum-based doublet chemotherapy; Envalfolimab plus platinum-based doublet chemotherapy for a total of 3-4 cycles of neoadjuvant therapy (determined by the investigator), Envafolimab will be administered after surgery at 600 mg every 3 weeks(Q3W) for 16 cycles at most.	Drug: Envalfolimab subcutaneously injected+Platinum-based doublet chemotherapy intravenous injection; The subjects receive Envafolimab/placebo treatment with a dosage of 600 mg/3 ml subcutaneously injected every 3 weeks.It will last about 3-4 cycles before surgery and 16 cycles after surgery.; Other Names: Experimental
Active Comparator: Placebo plus platinum-based doublet chemotherapy; Placebo plus platinum-based doublet chemotherapy for a total of 3-4 cycles of neoadjuvant therapy (determined by the investigator), placebo will be administered after surgery every 3 weeks(Q3W) for 16 cycles at most.	Drug: placebo subcutaneously injected +Platinum-based doublet chemotherapy intravenous injection; The subjects received platinum-based doublet chemotherapy on day 1 of every cycle. It's 3 weeks per cycle and lasts 3-4 cycles before surgery.; Other Names: Active Comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MPR by BIPR	MPR rate is defined as the percentage of participants having ≤10% viable tumor cells in the resected primary tumor and all resected lymph nodes following completion of neoadjuvant therapy (evaluated by BIPR)	Up to 5 years
EFS by BIRC	EFS is defined as the time from randomization until the occurrence of events leading to inoperable disease progression, post-operative disease progression (BIRC assessment based on RECIST 1.1) or recurrence/metastasis, or death from any cause.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR	pCR rate is defined as the percentage of participants having an absence of residual invasive cancer in resected lung specimens and lymph nodes following completion of neoadjuvant therapy, assessed by BIPR;	Up to 5 years
DFS	DFS is defined as the time from post-surgery to radiographic disease progression, local or distant recurrence, or death from any cause, assessed by BIRC;	Up to 5 years
OS	OS is defined as the time from randomization until death from any cause.;	Up to 5 years
EFS	EFS is defined as the time from randomization until the occurrence of events leading to inoperable disease progression, post-operative disease progression or recurrence/metastasis, or death from any cause., assessed by investigator;	Up to 5 years
Explore the quality of life for subjects by EORTC QLQ-C30	All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.	Up to 5 years
Explore the quality of life for subjects by EORTC QLQ-LC13	All of the scales and single-item measures range in score from 0 to 100. A high score for the scales and single items represents a high level of symptomatology or problems.	Up to 5 years
PD-L1, ctDNA	To explore the correlation between clinical efficacy and tumor tissue sample biomarkers (such as PD-L1 level, etc.) and blood sample biomarkers (such as ctDNA level, etc.)	Up to 5 years

Collaborators and Investigators

• Sponsor: 3D Medicines (Sichuan) Co., Ltd.
• Investigators: Principal Investigator: Changli Wang, Tianjin Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2023
• Primary Completion (Estimated): December 30, 2025
• Study Completion (Estimated): September 30, 2027

Study Registration Dates

• First Submitted: October 25, 2023
• First Submitted That Met QC Criteria: November 3, 2023
• First Posted (Actual): November 9, 2023

Study Record Updates

• Last Update Posted (Estimated): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Envafolimab
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: KN035-CN-017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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