Non Small Cell Lung Cancer Metastatic
Conditions
Keywords
Metastatic NSCLC, Advanced lung malignancy
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.
Interventions
BIOLOGICALTG4010
1 dose (1x1E+08) Subcutaneous injection/week over 6 weeks then 1 dose/3 weeks
DRUGChemotherapy
Pemetrexed/Cisplatin or Carboplatin Pemetrexed maintenance
DRUGNivolumab
360 mg IV administration every 3 weeks
Sponsors
Bristol-Myers Squibb
Transgene
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Principal Inclusion Criteria: * 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 Principal
Exclusion criteria
* 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 * Pregnant or nursing (lactating) women * Patients with an organ allograft * Any known allergy to eggs, gentamicin or history of allergy or hypersensitivity to study drug components * Participation in a clinical study with an investigational product within 4 weeks prior to the start of the study treatments
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 15 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | 28 months | 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. |
| Disease Control Rate (DCR) | 15 months | 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 | 28 months | 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. |
| Duration of Overall Response (DoR) | 28 months | Time from first documented response (complete response or partial response) until documented disease progression or death due to lung cancer. |
| Number of Participants With Adverse Events or Abnormalities | 28 months | 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. |
Countries
Belgium, France, Hungary, United States
Participant flow
Recruitment details
The study was conducted at 2 study sites in United States, 4 sites in France, 2 sites in Hungary and 1 site in Belgium.
Pre-assignment details
A total of 44 participants were enrolled and treated with at least one administration of each study drug.
Participants by arm
| Arm | Count |
|---|---|
| TG4010/Chemotherapy/Nivolumab 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 | 44 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
Baseline characteristics
| Characteristic | TG4010/Chemotherapy/Nivolumab | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 16 Participants | — |
| Age, Categorical Between 18 and 65 years | 28 Participants | — |
| Age, Continuous | 61.7 years STANDARD_DEVIATION 8.64 | — |
| Body Mass Index (BMI) | 24.4 kg/m^2 | — |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ECOG PS 0 | 21 participants | — |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ECOG PS 1 | 23 participants | — |
| PD-L1 percentage of stained cells <1 | 22 Participants | — |
| PD-L1 percentage of stained cells 1 - <50 | 22 Participants | — |
| PD-L1 percentage of stained cells ≥50 | 0 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment Belgium | 6 participants | — |
| Region of Enrollment France | 26 participants | — |
| Region of Enrollment Hungary | 6 participants | — |
| Region of Enrollment United States | 6 participants | — |
| Sex: Female, Male Female | 17 Participants | — |
| Sex: Female, Male Male | 27 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 28 / 44 |
| other Total, other adverse events | 43 / 44 |
| serious Total, serious adverse events | 28 / 44 |
Outcome results
Primary
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.
Time frame: 15 months
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TG4010/Chemotherapy/Nivolumab | Objective Response Rate (ORR) | 32.5 percentage of participants |
Secondary
Disease Control Rate (DCR)
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).
Time frame: 15 months
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TG4010/Chemotherapy/Nivolumab | Disease Control Rate (DCR) | 75.0 percentage of participants |
Secondary
Duration of Overall Response (DoR)
Time from first documented response (complete response or partial response) until documented disease progression or death due to lung cancer.
Time frame: 28 months
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TG4010/Chemotherapy/Nivolumab | Duration of Overall Response (DoR) | 74.9 Weeks |
Secondary
Number of Participants With Adverse Events or Abnormalities
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.
Time frame: 28 months
Population: Safety population (all treated participants)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TG4010/Chemotherapy/Nivolumab | Number of Participants With Adverse Events or Abnormalities | Adverse events | 44 Participants |
| TG4010/Chemotherapy/Nivolumab | Number of Participants With Adverse Events or Abnormalities | Serious adverse events | 28 Participants |
| TG4010/Chemotherapy/Nivolumab | Number of Participants With Adverse Events or Abnormalities | Adverse events of special interest | 37 Participants |
| TG4010/Chemotherapy/Nivolumab | Number of Participants With Adverse Events or Abnormalities | Immune-mediated adverse events | 14 Participants |
| TG4010/Chemotherapy/Nivolumab | Number of Participants With Adverse Events or Abnormalities | Grade 3/4 laboratories abnormalities | 31 Participants |
Secondary
Overall Survival
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 frame: 28 months
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TG4010/Chemotherapy/Nivolumab | Overall Survival | 14.9 Months |
Secondary
Progression Free Survival (PFS)
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.
Time frame: 28 months
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TG4010/Chemotherapy/Nivolumab | Progression Free Survival (PFS) | 5.7 Months |