E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-small cell lung cancer |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10059515 |
E.1.2 | Term | Non-small cell lung cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Part 1: Run-in
• To assess the safety and tolerability of the capmatinib and spartalizumab combination.
Part 2: Randomized
• To assess the overall survival of the combination of capmatinib and spartalizumab in comparison to docetaxel.
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E.2.2 | Secondary objectives of the trial |
• To assess the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), duration of response (DOR), and time to response (TTR) of the capmatinib and spartalizumab combination and that of docetaxel
• To assess the safety profile of capmatinib and spartalizumab combination therapy
• To characterize the pharmacokinetics of capmatinib and spartalizumab as a combination therapy in this patient population
• To evaluate the prevalence and incidence of immunogenicity
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
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 |
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E.4 | Principal exclusion criteria |
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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Run-in Part: Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs and ECGs, dose interruptions, reductions, and dose intensity
Randomized Part: Overall Survival
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Run-in Part: During the first 8 weeks (56 days) of treatment
Randomized Part: Time from date of randomization to date of death due to any cause.
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E.5.2 | Secondary end point(s) |
Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), duration of response (DOR), and time to response (TTR) based on RECIST 1.1
Incidence and severity of AEs and SAEs
Pharmacokinetic parameters (e.g. Ctrough, Cmax, AUC)
Antidrug antibodies (ADA) prevalence at baseline and ADA incidence on treatment |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Two-part: Part 1 run-in phase and Part2 randomized phase |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Bulgaria |
China |
France |
Germany |
Greece |
Hong Kong |
Israel |
Italy |
Japan |
Korea, Republic of |
Lebanon |
Netherlands |
Romania |
Russian Federation |
Spain |
Turkey |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of study is defined as the earliest occurrence of one of the following:
· All subjects have died or discontinued from the study.
· Another clinical study becomes available that can continue to provide capmatinib and spartalizumab combination in this subject population, and all subjects ongoing are eligible to be transferred to that clinical study. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 23 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |