Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Carcinoma, Non-Small-Cell Lung

Carcinoma

Lung Neoplasms

Recurrence

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

All Drugs and Chemicals

Antineoplastic Agents

Analgesics

Vaccines

Nivolumab

Interleukin-2

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Analgesics, Non-Narcotic

Patients receive TG4010 SC once per week for courses 1-3 and every 2 weeks for courses thereafter and nivolumab IV over 30 minutes every 2 weeks. Courses repeat every 14 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

TG4010

Karen Kelly

This phase II trial studies how well TG4010 and nivolumab work in previously treated patients with non-small cell lung cancer. Vaccines that are made from a gene-modified virus, such as TG4010, may help the body build an effective immune response to kill tumor cells. Monoclonal antibodies, such as nivolumab, interfere with the ability of tumor cells to grow and spread. Giving TG4010 and nivolumab together may work better in previously treated patients with non-small cell lung cancer.

PRIMARY OBJECTIVES:

To evaluate the efficacy of nivolumab plus TG4010 (modified vaccinia virus Ankara \[MVA\]-human mucin 1 \[MUC1\]-interleukin-2 \[IL2\] vaccine) in previously treated patients with stage IV non squamous non-small cell lung cancer (NSCLC) with respect to objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

SECONDARY OBJECTIVES:

Define the safety and toxicity profile of nivolumab plus TG4010 by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.

Determine progression-free survival by RECIST 1.1.

Determine overall survival.

Determine the duration of response and the occurrence of responses over time.

Determine the rate and duration of stable disease.

Determine the disease control rate.

TG4010 and Nivolumab in Patients With Lung Cancer

Phase II Trial of TG4010 Plus Nivolumab in Previously Treated Patients With Metastatic Non-Small Cell Lung Cancer (NSCLC)

Proportions of patients with a best overall response of CR or PR will be presented with exact 95% confidence intervals and p-value associated to the binomial test (with null proportion as reference). Will be performed on the Evaluable patient set. The analysis will be repeated on intent-to-treat (ITT) for confirmation.

National Cancer Institute (NCI)

Transgene

Bristol-Myers Squibb

Principal Investigator

Micronutrients

Hematinics

Vitamins

Gemcitabine

Paclitaxel

Carboplatin

Bevacizumab

Pemetrexed

Albumin-Bound Paclitaxel

Cisplatin

Immunomodulating Agents

Erlotinib Hydrochloride

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

First-line therapy and maintenance therapy

TG4010 • TG4010 will be administered starting on Day 1 (D1) of Cycle 1 of chemotherapy and will be administered weekly for 6 weeks by subcutaneous (SC) injections and then once every 3 weeks until progression or discontinuation due to any reason.

Chemotherapy (and bevacizumab if prescribed), will be given as 21-day cycles for a minimum of 4 cycles and up to 6 cycles.

First line therapy:

* Non-squamous carcinoma: pemetrexed + cisplatin or paclitaxel + carboplatin +/- bevacizumab
* Squamous carcinoma: gemcitabine + cisplatin or paclitaxel + carboplatin

Maintenance therapy:

• Pemetrexed or erlotinib for eligible patients and according to labeling.

Placebo will be administered starting on D1 of Cycle 1 of chemotherapy and will be administered weekly for 6 weeks by SC injections and then once every 3 weeks until progression or discontinuation due to any reason.

* First line therapy: as in Arm 1
* Maintenance therapy: as in Arm 1

placebo

QUOIX Elisabeth, Prof

This is a Phase IIb/III randomized, double-blind, placebo-controlled study to compare the efficacy and safety of first-line therapy combined with TG4010 or placebo in stage IV non-small cell lung cancer (NSCLC).

TG4010 is a suspension of recombinant Modified Vaccinia virus strain Ankara (MVA strain) carrying coding sequences for human MUC1 antigen and human interleukin-2 (IL2). TG4010 has been developed for use as an immunotherapy in cancer patients whose tumors express the MUC1 antigen.

TG4010 is intended to induce a MUC1-specific cellular immune response and to produce a non-specific activation of several components of the immune system.

Phase IIB/III Of TG4010 Immunotherapy In Patients With Stage IV Non-Small Cell Lung Cancer

A Phase IIB/III Randomized, Double-blind, Placebo Controlled Study Comparing First Line Therapy With or Without TG4010 Immunotherapy Product in Patients With Stage IV Non-Small Cell Lung Cancer (NSCLC)

PFS is measured from date of randomization to radiographically documented progression according to RECIST 1.1 or death from any cause (whichever occurs first). Participants alive and without disease progression or lost to follow-up will be censored at the date of their last radiographic assessment.

OS is measured from date of randomization to date of death from any cause.

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

Pemetrexed/Cisplatin or Carboplatin

Pemetrexed maintenance

Chemotherapy

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.

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)

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

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.

Time from the date of the first study drug administration to the date of first documented tumor progression or death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

The Kaplan-Meier estimator was used to estimate median PFS and its confidence interval.

Percentage of participants whose best overall response is either complete response, partial response or stable disease. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT scan or MRI: Complete Response (CR), Disappearance of all target and non-target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions and no measurable non-target lesions; Stable disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD).

Overall Survival (OS) is defined as the time from the first study drug administration to the date of death due to any cause.

The Kaplan-Meier estimator was used to estimate median OS and its confidence interval.

Time from first documented response (complete response or partial response) until documented disease progression or death due to lung cancer.

The assessment of safety of the combination was based mainly on the frequency of adverse events, serious adverse events, adverse events of special interest (Injection site reaction, fatigue, pyrexia, infusion-related reactions and diarrhea), immune-mediated adverse events and laboratories abnormalities.

TG4010: 1 dose (1x1E+08) Subcutaneous injection/week over 6 weeks then 1 dose/3 weeks

Chemotherapy: Pemetrexed/Cisplatin or Carboplatin

Pemetrexed maintenance

Nivolumab: 360 mg IV administration every 3 weeks

TG4010/Chemotherapy/Nivolumab

Age, Categorical

Age, Continuous

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

Belgium

Hungary

United States

France

Region of Enrollment

ECOG PS 0

ECOG PS 1

ECOG PS 0: Fully active, able to carry on all pre-disease performance without restriction ECOG PS 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature

Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)

Body Mass Index (BMI)

Participants were assessed for their PD-L1 tumor expression level by immunohistochemistry assay (method Dako PD-L1 IHC 22C3 pharmDx assay kit) using tumor tissue from an archival or newly obtained biopsy. Participants with PD-L1 expression ≤50% of tumor cells were eligible to the study.

PD-L1 percentage of stained cells

Director of Medical Affairs

The Evaluable Patient's Population is the primary population for efficacy analyses. Evaluable Patient's Population consists of all participants without major protocol deviation and have at least one baseline and one post-baseline evaluable CT-scan after study treatment start except early disease progression and death due to lung cancer.

Objective Response Rate (ORR)

Progression Free Survival (PFS)

Disease Control Rate (DCR)

Overall Survival

Responders: all evaluable participants with complete response or partial response. The start date was the date of first documented response (complete response or partial response) and the end date was the date of first documented disease progression. If no progression has been observed at the cut-off date of analysis or at the date when a subsequent cancer therapy was started, duration of response was censored at the date of the last evaluable tumor assessment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
TG4010 and Nivolumab in Patients With Lung Cancer	NCT02823990	Recurrent Non-S... Stage I Non-Sma... Stage II Non-Sm... Stage IIIA Non-... Stage IIIB Non-... Stage IV Non-Sm...	TG4010 Nivolumab	18 Years -	University of California, Davis
Phase IIB/III Of TG4010 Immunotherapy In Patients With Stage IV Non-Small Cell Lung Cancer	NCT01383148	Non-Small-Cell ...	TG4010 placebo	18 Years -	Transgene
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	Non Small Cell ...	TG4010 Chemotherapy Nivolumab	18 Years -	Transgene
TG4010 and Nivolumab in Patients With Lung Cancer	NCT02823990	Recurrent Non-S... Stage I Non-Sma... Stage II Non-Sm... Stage IIIA Non-... Stage IIIB Non-... Stage IV Non-Sm...	TG4010 Nivolumab	18 Years -	University of California, Davis

Spots Global Cancer Trial Database for tg4010

Every month we try and update this database with for tg4010 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for tg4010

Every month we try and update this database with for tg4010 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for tg4010 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.