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

Sponsor

Fudan University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05910034

Collaborator

(none)

132

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Advanced Non-Small Cell Lung Cancer	Drug: Trilaciclib+Envafolimab+Docetaxel Drug: Envafolimab+Docetaxel Drug: Docetaxel	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

132 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jul 1, 2023

Anticipated Primary Completion Date :

Dec 30, 2025

Anticipated Study Completion Date :

Jun 30, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Trilaciclib+Envafolimab+Docetaxel Trilaciclib:240mg/m2 IV d1,within 4h before chemotherapy; Envafolimab:300mg SC d1,Q3W; Docetaxel:75mg/m2 IV d1, Q3W	Drug: Trilaciclib+Envafolimab+Docetaxel 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.
Experimental: Envafolimab+Docetaxel Envafolimab:300mg SC d1,Q3W; Docetaxel:75mg/m2 IV d1, Q3W	Drug: Envafolimab+Docetaxel 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.
Experimental: Docetaxel Docetaxel: 75mg/m2 IV d1, Q3W	Drug: Docetaxel 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.

Arm

Intervention/Treatment

Experimental: Trilaciclib+Envafolimab+Docetaxel

Trilaciclib:240mg/m2 IV d1,within 4h before chemotherapy; Envafolimab:300mg SC d1,Q3W; Docetaxel:75mg/m2 IV d1, Q3W

Drug: Trilaciclib+Envafolimab+Docetaxel

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.

Experimental: Envafolimab+Docetaxel

Envafolimab:300mg SC d1,Q3W; Docetaxel:75mg/m2 IV d1, Q3W

Drug: Envafolimab+Docetaxel

Experimental: Docetaxel

Docetaxel: 75mg/m2 IV d1, Q3W

Drug: Docetaxel

Outcome Measures

Primary Outcome Measures

PFS [12 months after the last subject participating in]
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.

Secondary Outcome Measures

ORR [12 months after the last subject participating in]
The proportion of subjects with complete response (CR) and partial response (PR) in total subjects.
DCR [12 months after the last subject participating in]
The proportion of subjects with complete response (CR), partial response (PR)and stable disease in(SD) in total subjects.
DoR [12 months after the last subject participating in]
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.
OS [24 months after the last subject participating in]
Defined as the time from randomization to all-cause death.
QOL [24 months after the last subject participating in]
Quality of life was assessed using the EQ-5D-5L scale
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 [24 months after the last subject participating in]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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