Envafolimab Plus Docetaxel In Combination With or Without Trilaciclib Versus Docetaxel in Advanced NSCLC

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of Envafolimab Plus Docetaxel in combination with or without Trilaciclib versus docetaxel IN patients with advanced non-small cell lung cancer previously treated with a PD-1 inhibitor combined with chemotherapy

Detailed Description
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Trilaciclib indication: Trilaciclib, a CDK4/6 inhibitor, was used before chemotherapy to reduce the incidence of bone marrow suppression, approved by FDA and NMPA for small cell lung cancer in 2021 and in 2022. Envafolimab indication: Envafolimab, a PD-L1 inhibitor, was used for unresectable or metastatic, MSI-H or dMMR, Adult patients with advanced solid tumors, approved by NMPA in 2021.

Official Title
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The Study of Envafolimab Plus Docetaxel in Combination With or Without Trilaciclib Versus Docetaxel in Advanced NSCLC Previously Treated With a PD-1 Inhibitor Combined With Chemotherapy

Conditions
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Advanced Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Trilaciclib+Envafolimab+Docetaxel
* Drug: Envafolimab+Docetaxel
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects aged≥ 18 years old Metastatic or advanced (stage IV) NSCLC confirmed by tissue or pathology Patients with advanced NSCLC who had previously failed treatment with platinum-containing chemotherapy combined with PD-1 inhibitor Disease must be measurable by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).,and has at least one measurable lesion Patients with asymptomatic brain metastasis or whose symptoms are stable after treatment Patients who responded to initial therapy or whose disease was stable for at least 3 months Laboratory tests met the following criteria: Hemoglobin (Hb)≥100 g/L(female), ≥110g/L(male) Neutrophils (ANC)≥1.5×109/L platelet count (PLT)≥100×109/L Cr≤ 15mg/L or CrCl≥ 60 mL/min TBIL≤ 1.5×ULN ALT and AST ≤ 3 × ULN or ≤5× ULN(patients with liver metastases) Albumin ≥ 30 g/L Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 Estimated life expectancy of more than 12 weeks Women: All women with potential fertility must have negative serum pregnancy tests during the screening period and must have reliable contraception after signing the informed consent form until 3 months after the last dose Already signed an informed consent form Exclusion Criteria: Diagnosis of other malignancies than NSCLC within 5 years prior to the first dose administration (excluding radically treated cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, and/or radically resected carcinoma in situ) Toxicity not recovered to ≤ Grade 1 from prior anticancer therapy Previous treatment with PD-L1 inhibitors ≥grade 3 immune-related adverse reactions have occurred during previous PD-1 inhibitors treatment Patients with known or suspected interstitial pneumonia Patients with known positive driving genes(EGFR,ALK,ROS1) Have used or requirement of treatment with prednisone > 10 mg/day or equivalent systemic corticosteroids within 14 days prior to the first dose of study drug Administration of live attenuated vaccines within 28 days prior to the first study drug treatment or planned administration during the study Uncontrolled ischemic heart disease or clinically significant congestive heart failure (NYHA grade III or IV) Have stroke or cardiovascular events within 6 months prior to enrollment QTcF>480 msec or QTcF>500 msec(patients with ventricular pacemakers) Patients who have received hematopoietic stem cell or bone marrow transplants Allergic to the study drug or its ingredients Any other circumstances in which the researcher believes that the patient is not suitable to participate in this study

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trilaciclib+Envafolimab+Docetaxel<br>Trilaciclib:240mg/m2 IV d1,within 4h before chemotherapy; Envafolimab:300mg SC d1,Q3W; Docetaxel:75mg/m2 IV d1, Q3W | Drug: Trilaciclib+Envafolimab+Docetaxel<br>* This is a multi-arm, randomized, controlled, multicenter, Phase II clinical study. Participants randomly assigned at a 1:1:1 ratio to three groups, and will be treated until disease progression, intolerance, withdrawal of consent or completion determined by the investigator.<br>|
| Experimental: Envafolimab+Docetaxel<br>Envafolimab:300mg SC d1,Q3W; Docetaxel:75mg/m2 IV d1, Q3W | Drug: Envafolimab+Docetaxel<br>* This is a multi-arm, randomized, controlled, multicenter, Phase II clinical study. Participants randomly assigned at a 1:1:1 ratio to three groups, and will be treated until disease progression, intolerance, withdrawal of consent or completion determined by the investigator.<br>|
| Experimental: Docetaxel<br>Docetaxel: 75mg/m2 IV d1, Q3W | Drug: Docetaxel<br>* This is a multi-arm, randomized, controlled, multicenter, Phase II clinical study. Participants randomly assigned at a 1:1:1 ratio to three groups, and will be treated until disease progression, intolerance, withdrawal of consent or completion determined by the investigator.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | Progression-free survival (PFS per RECIST 1.1) is defined as the time from randomization to the date of first documentation of disease progression or death, whichever occurs first. | 12 months after the last subject participating in | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | The proportion of subjects with complete response (CR) and partial response (PR) in total subjects. | 12 months after the last subject participating in | 
| DCR | The proportion of subjects with complete response (CR), partial response (PR)and stable disease in(SD) in total subjects. | 12 months after the last subject participating in | 
| DoR | DoR (per RECIST 1.1) is defined as the time from the date for first documented response of complete response (CR) or partial response (PR) to the date of first documented of disease progression or death, whichever occurs first. | 12 months after the last subject participating in | 
| OS | Defined as the time from randomization to all-cause death. | 24 months after the last subject participating in | 
| QOL | Quality of life was assessed using the EQ-5D-5L scale | 24 months after the last subject participating in | 
| The incidence of Subjects With Treatment-Emergent Adverse Events (TEAEs) According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0 | TEAEs will be defined as the adverse events (AEs) that occur between first dose of study drug administration and 28 days after the last dose of study drug administration | 24 months after the last subject participating in | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Trilaciclib, Envafolimab, NSCLC, Second-line Treatment