Advanced adenocarcinoma of the lung MedDRA version: 20.0 Level: LLT Classification code 10001164 Term: Adenocarcinoma lung stage III System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classification code 10001165 Term: Adenocarcinoma lung stage IV System Organ Class: 100000004864
Conditions
Interventions
Product Name: JNJ-64041757
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: JNJ-757
Other descriptive name: JNJ-64041757
Concentration unit: CFU/ml colony forming unit(s)/millilitre
Con
Sponsors
Janssen-Cilag International NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Histologically documented adenocarcinoma of the lung - Stage IIIB or Stage IV disease - Biopsy material available for central assessment of PD-L1 and mesothelin - In Phase 2 only: Mesothelin-positive status - ECOG performance status of 0 or 1 - Progressive disease during or after platinum-based doublet chemotherapy, administered in the metastatic setting - Adequate bone marrow function, defined as: • Absolute neutrophil count (ANC) =1500/µL (or 1.5×10 to the power of 9/L) • Platelets =100,000/µL (or 100×10 to the power of 9/L) • Hemoglobin =10.0 g/dL - Adequate hepatic function, defined as: • Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) = 1.5 times the upper limit of normal (ULN) • Total serum bilirubin =1.5xULN - Adequate renal function, defined as: • Calculated creatinine clearance =40 mL/min using the Cockcroft-Gault equation - A woman of childbearing potential must have a negative serum (ß-human chorionic gonadotropin [ß-hCG]) or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of hCG) within 14 days before the first dose of nivolumab and a second negative test within 24 hours before the first dose of nivolumab. - Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for subject participating in clinical studies. Further details see protocol - A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction while on the study agent and for 5 months after the last dose of study agent - To avoid risk of drug exposure through the ejaculate (even men with vasectomies), subjects must use a condom during sexual activity while on the study agent and for 5 months (female subjects) or 7 months (male subjects) after the last dose of study agent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 4 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 11
Exclusion criteria
Exclusion criteria: - Untreated brain metastases or other active central nervous system (CNS) metastases. Subjects with a history of brain metastasis must have completed treatment for brain metastasis for at least 28 days, and be neurologically stable and off steroids before enrollment (Phase 1b) or randomization (Phase 2). - Tumor with activating EGFR mutation or ALK translocation (EGFR and ALK results must be confirmed in the Screening Period for all non-smokers). - More than 1 prior line of chemotherapy for metastatic disease (not including therapy given in the maintenance setting, or neoadjuvant or adjuvant therapy for locally advanced disease). - History of symptomatic interstitial lung disease. - History of disallowed therapies, as follows: • In Phase 1b only: Prior exposure to anti-PD1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) antibody within 28 days before the first dose of study agent • In Phase 2 only: Prior exposure to anti-PD1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) antibody • History of listeriosis or vaccination with a Listeria-based vaccine or prophylactic vaccine (eg, influenza, pneumococcal, diphtheria, tetanus, and pertussis [dTP/dTAP]) within 28 days before the first dose of study agent • Chemotherapy within 28 days before the first dose of study agent • Radiation within 14 days before the first dose of study agent (exception: palliative radiotherapy for pain can be used = 7 days before or after study agent) - Any uncontrolled active systemic infection, active noninfectious pneumonitis, or any life-threatening illness, medical condition, or organ system dysfunction - Any active autoimmune disease or a documented history of autoimmune disease - History of any other condition that may require the initiation of anti-tumor necrosis factor alpha (TNFa) therapies or other immunosuppressant medications during the study. - Known allergy to both penicillin/amoxicillin and trimethoprim/sulfamethoxazole. - Concurrent treatment with anti-TNFa therapies, systemic corticosteroids (prednisone dose >10 mg per day or equivalent), or other immunosuppressive drugs <14 days before randomization. Steroids that are topical, inhaled, nasal (spray), or ophthalmic solution are permitted. - Positive test result for human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS). - History of major implant(s) or device(s) - History of clinically significant cardiovascular disease within 6 months of randomization - Known active or chronic hepatitis B or hepatitis C as demonstrated by hepatitis B surface antigen (HBsAg) positivity and/or anti-hepatitis C virus (HCV) positivity, respectively. Subjects with clinically active or chronic liver disease, including liver cirrhosis, are also excluded. - Active second malignancy within 2 years prior to randomization (exceptions see protocol) - Evidence of active viral, bacterial, or systemic fungal infection requiring systemic treatment within 7 days before the first dose of the study agent. - Known allergies, hypersensitivity, or intolerance to JNJ-757 or nivolumab or its excipients
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate whether the efficacy of JNJ-757 combined with nivolumab is better than the efficacy of nivolumab monotherapy for subjects with mesothelin-positive relapsed/refractory Stage IIIB or Stage IV adenocarcinoma of the lung, by PD-L1 level;Secondary Objective: - To compare the clinical benefit of JNJ-757 combined with nivolumab versus nivolumab monotherapy - To evaluate the safety of JNJ-757 - To correlate PD-L1 levels with clinical activity - To assess the blood culture and shedding profile of JNJ-757 - To assess the pharmacokinetics and immunogenicity of nivolumab;Primary end point(s): Objective response rate (complete response plus partial response, based on RECIST 1.1 criteria);Timepoint(s) of evaluation of this end point: Every 8 weeks (±7d) during the first year, and then every 12 weeks (±7d) thereafter. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Disease control rate (stable disease for 16 weeks, complete response, or partial response) - Duration of objective response - Progression-free survival - Overall survival - Incidence of adverse events;Timepoint(s) of evaluation of this end point: - DCR, DOR, PFS: Every 8 weeks (±7d) during the first year, and then every 12 weeks (±7d) thereafter. - OS: throughout the whole study, after discontinuation of treatment every 3 months - Adverse events: throughout the whole study until 100 days after the last dose of nivolumab | — |
Countries
Belgium, Spain, United States
Contacts
Public ContactPC-CTRS
PAREXEL International S.L.
Outcome results
None listed