A Study Evaluating the Efficacy and the Safety of First-line Chemotherapy Combined With the Therapeutic Vaccine Named TG4010 and Nivolumab in Patients With Advanced Non-squamous Non-Small Cell Lung Cancer (NSCLC)

NCT03353675 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: TG4010.24
• Study Type: interventional
• Target: 44
• Locations: 4 countries
• Sites: 9

Brief Summary

This is a multicenter, single arm, open label phase II study in treatment-naïve for advanced stage of the disease and immunotherapy-naïve patients with advanced non-squamous NSCLC and with \< 50% of tumor cells expressing programmed death-ligand 1 (PD-L1) by immunohistochemical (IHC) staining.

Conditions

Non Small Cell Lung Cancer Metastatic

Keywords

Metastatic NSCLC; Advanced lung malignancy

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Percentage of participants whose best overall response is complete response or partial response using RECIST 1.1. confirmed by a second scan no less than 4 weeks after the criteria for response are first met. Complete response: disappearance of all lesions and no new lesions. Partial response: decrease of at least 30% in the sum of the diameters of measurable lesions taking as reference the baseline sum of diameters, no progression of non-measurable lesions and no new lesions.

  15 months

Secondary Outcomes (5)

• Progression Free Survival (PFS)

  28 months

• Disease Control Rate (DCR)

  15 months

• Overall Survival

  28 months

• Duration of Overall Response (DoR)

  28 months

• Number of Participants With Adverse Events or Abnormalities

  28 months

Study Arms (1)

TG4010/Chemotherapy/Nivolumab

EXPERIMENTAL

Biological: TG4010; Drug: Chemotherapy; Drug: Nivolumab

Interventions

TG4010 BIOLOGICAL

1 dose (1x1E+08) Subcutaneous injection/week over 6 weeks then 1 dose/3 weeks

TG4010/Chemotherapy/Nivolumab

Chemotherapy DRUG

Pemetrexed/Cisplatin or Carboplatin Pemetrexed maintenance

TG4010/Chemotherapy/Nivolumab

Nivolumab DRUG

360 mg IV administration every 3 weeks

TG4010/Chemotherapy/Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female or male patients age \> 18 years-old
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 at study entry
• Life expectancy of at least 3 months
• Histologically confirmed non-squamous NSCLC (adenocarcinoma, large cell carcinoma, undifferentiated carcinoma or other)
• Stage IIIB-IV cancer or delayed relapse of any stage not amenable to surgery or radiotherapy with curative intent.
• PD-L1 expression by immunohistochemistry in \< 50% of tumor cells
• Patients must be chemotherapy-naïve for the advanced stage of the disease. Previous neoadjuvant and/or adjuvant chemotherapy is allowed for patients who successfully underwent complete radical surgery and if last treatment was administered more than 12 months prior to the start of the study treatment.
• At least one measurable lesion by CT scan based on RECIST 1.1 performed within 28 days prior to start of study treatment
• Adequate hematological, hepatic, and renal functions
• Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 72 hours prior to the start of study drug
• WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s) plus 5 half-lives of study drug plus 30 days for a total of 5 months posttreatment completion. Highly effective contraception are defined in the protocol.
• Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug (s) plus 5 half-lives of study drug (s) plus 90 days for a total of 7 months post-treatment completion

You may not qualify if:

• Patients having central nervous system (CNS) metastases
• Patients with pericardial effusion
• Prior exposure to cancer immunotherapy including cancer vaccines, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-cytotoxic T-Lymphocyte antigen- 4 antibody or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways
• Patients with epidermal growth factor receptor (EGFR) activating mutations or anaplastic lymphoma kinase (ALK)- rearrangements leading to eligibility for tyrosine kinase inhibitor (TKI) treatment (tests mandatory)
• Prior history of other malignancy except basal cell carcinoma of the skin, cervical intra epithelial neoplasia, and other cancer curatively treated with no evidence of disease for at least 3 years
• Patients with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of start of study treatment
• Patients with an active, known or suspected autoimmune disease
• Patient with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
• Patients with grade ≥ 2 neuropathy
• Signs or symptoms of infection within 14 days prior to start of study treatment or active infection requiring systemic therapy
• Positive serology for HIV or hepatitis C virus (HCV); presence in the serum of the antigens hepatitis B (HBs) at baseline
• Patient with any underlying medical condition that the treating physician considers might be aggravated by treatment or which is not controlled (e.g., elevated troponin or creatinine, uncontrolled diabetes)
• History of cardiovascular conditions within 12 months of enrollment
• Left ventricular ejection fraction less than the Lower Limit of Normal as assessed by echocardiography (or multigated acquisition (MUGA) scan)
• Patient with major surgery or radiotherapy within 3 weeks prior to the start of the study treatment. However, prior surgery or radiation therapy aimed at local palliation or attempted local disease control (except in case of thoracic radiotherapy) is permitted but has to be completed 2 weeks before treatment start

Sponsors & Collaborators

• Transgene: lead
• Bristol-Myers Squibb: collaborator

Study Sites (9)

Charlotte

Charlotte, North Carolina, 28204, United States

Location

Nashville

Nashville, Tennessee, 37203, United States

Location

Libramont

Libramont, Belgium

Location

Créteil

Créteil, France

Location

Mulhouse

Mulhouse, France

Location

Rennes

Rennes, France

Location

Strasbourg

Strasbourg, France

Location

Budapest

Budapest, Hungary

Location

Szekesfehervar

Székesfehérvár, Hungary

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

TG4010; Drug Therapy; Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Director of Medical Affairs
• Organization: Transgene

clinical.trials@transgene.fr

+ 33 (0)3 88 27 91 00

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2017
• First Posted: November 27, 2017
• Study Start: January 5, 2018
• Primary Completion: November 20, 2019
• Study Completion: February 17, 2021
• Last Updated: January 11, 2022
• Results First Posted: January 11, 2022

Record last verified: 2021-12

Locations

BE (1); HU (2); US (2); FR (4)