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

Advanced Non-Small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05910034
• Other study ID #: SMA-NSCLC-012
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 1, 2023
• Est. completion date: June 30, 2026

Study information

• Verified date: June 2023
• Source: Fudan University
• Contact: Wang Jialei, doctor
• Phone: 021-6417 5590
• Email: luwangjialei[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 132
• Est. completion date: June 30, 2026
• Est. primary completion date: December 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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:

1. Hemoglobin (Hb)=100 g/L(female), =110g/L(male)

2. Neutrophils (ANC)=1.5×109/L

3. platelet count (PLT)=100×109/L

4. Cr= 15mg/L or CrCl= 60 mL/min

5. TBIL= 1.5×ULN

6. ALT and AST = 3 × ULN or =5× ULN(patients with liver metastases)

7. 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

Related Conditions & MeSH terms

• Advanced Non-Small Cell Lung Cancer
• Carcinoma, Non-Small-Cell Lung

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

References & Publications (7)

Boyero L, Sanchez-Gastaldo A, Alonso M, Noguera-Ucles JF, Molina-Pinelo S, Bernabe-Caro R. Primary and Acquired Resistance to Immunotherapy in Lung Cancer: Unveiling the Mechanisms Underlying of Immune Checkpoint Blockade Therapy. Cancers (Basel). 2020 De — View Citation

Cabrita R, Mitra S, Sanna A, Ekedahl H, Lovgren K, Olsson H, Ingvar C, Isaksson K, Lauss M, Carneiro A, Jonsson G. The Role of PTEN Loss in Immune Escape, Melanoma Prognosis and Therapy Response. Cancers (Basel). 2020 Mar 21;12(3):742. doi: 10.3390/cancer — View Citation

Herbst RS, Garon EB, Kim DW, Cho BC, Gervais R, Perez-Gracia JL, Han JY, Majem M, Forster MD, Monnet I, Novello S, Gubens MA, Boyer M, Su WC, Samkari A, Jensen EH, Kobie J, Piperdi B, Baas P. Five Year Survival Update From KEYNOTE-010: Pembrolizumab Versu — View Citation

Law AMK, Valdes-Mora F, Gallego-Ortega D. Myeloid-Derived Suppressor Cells as a Therapeutic Target for Cancer. Cells. 2020 Feb 27;9(3):561. doi: 10.3390/cells9030561. — View Citation

Morimoto Y, Kishida T, Kotani SI, Takayama K, Mazda O. Interferon-beta signal may up-regulate PD-L1 expression through IRF9-dependent and independent pathways in lung cancer cells. Biochem Biophys Res Commun. 2018 Dec 9;507(1-4):330-336. doi: 10.1016/j.bbrc.2018.11.035. Epub 2018 Nov 14. — View Citation

Roselli M, Cereda V, di Bari MG, Formica V, Spila A, Jochems C, Farsaci B, Donahue R, Gulley JL, Schlom J, Guadagni F. Effects of conventional therapeutic interventions on the number and function of regulatory T cells. Oncoimmunology. 2013 Oct 1;2(10):e27 — View Citation

Travis WD, Brambilla E, Nicholson AG, Yatabe Y, Austin JHM, Beasley MB, Chirieac LR, Dacic S, Duhig E, Flieder DB, Geisinger K, Hirsch FR, Ishikawa Y, Kerr KM, Noguchi M, Pelosi G, Powell CA, Tsao MS, Wistuba I; WHO Panel. The 2015 World Health Organizati — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	ORR	The proportion of subjects with complete response (CR) and partial response (PR) in total subjects.	12 months after the last subject participating in
Secondary	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
Secondary	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
Secondary	OS	Defined as the time from randomization to all-cause death.	24 months after the last subject participating in
Secondary	QOL	Quality of life was assessed using the EQ-5D-5L scale	24 months after the last subject participating in
Secondary	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