Study of safety and efficacy of INC280 in combination with PDR001, compared to chemotherapy, in advanced/ metastatic non-small cell lung cancer patients with no EGFR mutations or ALK rearrangements.
- Conditions
- on-small cell lung cancerMedDRA version: 20.0Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-001420-19-BE
- Lead Sponsor
- ovartis Pharma AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 105
1. Written informed consent must be obtained prior to any screening procedures
2. Adult = 18 years old at the time of informed consent
3. Histologically confirmed locally advanced/metastatic (stage IIIB or IV per AJCC/IASLC v. 8) NSCLC
4. Histologically or cytologically confirmed diagnosis of NSCLC that is both EGFR wt status and ALK- negative rearrangement status:
• Patients with NSCLC of pure squamous cell histology can enter screening without EGFR mutation or ALK rearrangement testing or result; however, patients with pure squamous cell histology who are known to have EGFR mutations in exons 19 or 21 or ALK rearrangements will be excluded
5. Patients must have demonstrated progression of locally advanced/ metastatic NSCLC (stage IIIB, not amenable for definitive chemo-irradiation, or stage IV) following one prior platinum doublet and one prior PD-(L)1 checkpoint inhibitor (either alone or in combination)
• Maintenance therapy given after first-line chemotherapy will be considered as part of the first-line therapy if given to patients with documented response or stable disease before starting the maintenance therapy.
• Neo-adjuvant and adjuvant systematic therapies will count as one prior line of systemic treatment for the advanced stage if relapse occurred within 12 months from the end of the neoadjuvant or adjuvant systemic therapy.
• The most recent line of therapy should include a PD-(L)1 checkpoint inhibitor (either alone or in combination)
6. Patients must be candidates for single agent chemotherapy with docetaxel
7. Patients must have recovered from all toxicities related to prior anticancer therapies to grade = 1 (CTCAE v 5.0). Patients with any grade of alopecia are allowed to enter the study
8. At least one measurable lesion as defined by RECIST 1.1. A previously irradiated site lesion may only be counted as a target lesion if there is clear sign of progression since the irradiation
9. Patients must have adequate organ function including the following laboratory values at the screening visit:
• Absolute neutrophil count (ANC) = 1.5 x 109/L without growth factor support
• Platelets = 75 x 109/L
• Hemoglobin (Hgb) = 9 g/dL
• Calculated creatinine clearance (using Cockcroft-Gault formula) = 45 mL/min
• Total bilirubin = 1.5 x ULN
• Aspartate transaminase (AST) = 3 x ULN, except for patients with liver metastasis, who may only be included if AST = 5 x ULN
• Alanine transaminase (ALT) = 3 x ULN, except for patients with liver metastasis, who may only be included if ALT = 5 x ULN
• Alkaline phosphatase (ALP) = 5.0 x UL
• Asymptomatic serum amylase = Grade 2. Patients with Grade 1 or Grade 2 serum amylase at the beginning of the study must be confirmed to have no signs and/or symptoms suggesting pancreatitis or pancreatic injury (e.g., elevated P-amylase, abnormal imaging findings of pancreas, etc.)
• Serum lipase = ULN
• Fasting plasma glucose = 160 mg/dL (= 8.9 mmol/L)
10. ECOG performance status (PS) of 0 or 1
11. Willing and able to comply with scheduled visits, treatment plan and laboratory tests
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 42
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 63
1. Prior treatment with a MET inhibitor or HGF-targeting therapy
2. Any untreated central nervous system (CNS) lesion. However, patients are eligible if all known CNS lesions have been treated with radiotherapy or surgery and remained stable for = 4 weeks after treatment. Patients must be off corticosteroid therapy for = 2 weeks
3. Carcinomatous meningitis.
4. Use of hematopoietic colony-stimulating growth factors (e.g. G-CSF, GMCSF, M-CSF), thrombopoietin mimetics or erythroid stimulating agents = 2 weeks prior start of study treatment. If erythroid stimulating agents were initiated more than 2 weeks prior to the first dose of study treatment and the patient is on a stable dose, they can be maintained
5. Use of any live vaccines against infectious diseases within 3 months of initiation of study treatment. Patients randomized to the spartalizumab containing arm will need to comply with this criterion for the whole duration of the study treatment
6. Patients receiving treatment with any enzyme-inducing anticonvulsant that cannot be discontinued at least 1 week before first dose of study treatment, and for the duration of the study. Patients on non-enzyme-inducing anticonvulsants are eligible
7. Systemic chronic steroid therapy (= 10 mg/day prednisone or equivalent) or any immunosuppressive therapy 7 days prior to planned date of first dose of study treatment. Topical, inhaled, nasal and ophthalmic steroids are allowed. Steroid premedication for docetaxel infusion does not apply
8. Thoracic radiotherapy to lung fields = 4 weeks prior to starting Cycle 1 Day 1 or patients who have not recovered from radiotherapy-related toxicities. For all other anatomic sites (including radiotherapy to thoracic vertebrae and ribs), radiotherapy = 2 weeks prior to Cycle 1 Day 1, or patients who have not recovered from radiotherapy-related toxicities.
9. Major surgery within 4 weeks prior to starting study treatment (2 weeks for resection of brain metastases), or patients who have not recovered from the side effects of such a procedure. Video-assisted thoracic surgery (VATS) and mediastinoscopy will not be counted as major surgery and patients can be enrolled in the study =1 week after the procedure
10. Impairment of GI function or GI disease that may significantly alter the absorption of capmatinib
11. Active, known or suspected autoimmune disease or a documented history of autoimmune disease. Note: patients with vitiligo, controlled type I diabetes mellitus on stable insulin dose, residual autoimmune-related hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
12. Previous anti-cancer and investigational agents within 4 weeks or = 5 x half-life of the agent (whichever is longer) before first dose of study treatment. If previous treatment is a monoclonal antibody or an anti PD-(L)1 checkpoint inhibitor, then the treatment must be discontinued at least 4 weeks before first dose of study treatment. If previous treatment is an oral targeted agent, then the treatment must be discontinued at least 5 x half-life of the agent
13. History of allogenic bone marrow or solid organ transplant
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method