Randomized Phase 3 Study of Sitravatinib in Combination with Nivolumab versus Docetaxel in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) Not Otherwise Specified with Disease Progression During or After Platinum-Based Chemotherapy and Checkpoint Inhibitor Treatment (SAPPHIRE)
Descrizione riassuntiva dello studio
This study will compare the efficacy of sitravatinib in combination with nivolumab to that of docetaxel in patients with non-small cell lung cancer who have previously progressed during or after chemotherapy and immunotherapy. Sitravatinib is an experimental drug that belongs to a class of drugs called "tyrosine kinase inhibitors." Sitravatinib is being developed as a potential treatment for various types of cancer. Nivolumab is an immunotherapy agent approved by Swissmedic that belongs to a class of drugs called "checkpoint inhibitors." Docetaxel is a chemotherapy agent approved by Swissmedic for the treatment of patients with advanced non-small cell lung cancer previously treated with platinum-based chemotherapy. Up to 532 patients are expected to participate in this study worldwide. 1 in 2 patients will receive treatment with nivolumab in combination with sitravatinib, administered in cycles of 28 days. Nivolumab will be administered by infusion for approximately 30 minutes at 240 mg every 2 weeks or 480 mg every 4 weeks, at the discretion of the investigator. Sitravatinib capsules will be administered orally at 100 mg once daily. 1 in 2 patients will receive docetaxel, administered intravenously at 75 mg/m2 for 1 hour or according to institutional practices, every 3 weeks. Patients will receive the study treatment until disease progression, until unacceptable adverse events occur, until the investigator's decision, until patient refusal, or until death.
(BASEC)
Intervento studiato
This multicenter Phase III clinical study aims to evaluate the efficacy and safety of sitravatinib in combination with nivolumab compared to docetaxel in patients with advanced non-small cell lung cancer who have already experienced disease progression during or after platinum-based chemotherapy and checkpoint inhibitors. Dexamethasone, as premedication for docetaxel, will be obtained locally by each center for patients receiving docetaxel. The study objectives include evaluating the safety of sitravatinib in combination with nivolumab, assessing the absorption rate of sitravatinib into the bloodstream and its elimination rate, as well as evaluating health-related quality of life. Several laboratory tests may be performed using tumor tissue or blood samples to understand how and why the drugs may work together in the treatment of lung cancer. These tests on tumor tissues and blood are optional.
(BASEC)
Malattie studiate
Advanced Non-Small Cell Lung Cancer (NSCLC) Not Otherwise Specified with Disease Progression During or After Platinum-Based Chemotherapy and Checkpoint Inhibitor Treatment
(BASEC)
Patients must be at least 18 years old and meet all of the following inclusion criteria to be eligible for inclusion in the study. 1. Diagnosis of non-small cell lung cancer (NSCLC) not otherwise specified. 2. Have received at least one but no more than two prior treatments in the context of advanced disease that may include: • Treatment with TIC (i.e., anti-PD-1/PD-L1) and platinum-based chemotherapy that may have been combined or implemented consecutively (i.e., platinum-based chemotherapy followed by a TIC). The last treatment must have included a TIC with radiographic disease progression during or after treatment. 3. Duration of the last TIC treatment of at least 4 months (120 days) from the first dose of the last TIC treatment to the date of radiographic disease progression. There are additional criteria that must be met to participate in this clinical study. The investigator will review these in detail until patients are included in this study. (BASEC)
Criteri di esclusione
Patients meeting any of the following criteria will not be included in the study: 1. Interruption of a prior TIC treatment more than 90 days before the randomization date. 2. Receipt of systemic anticancer treatment since the interruption of the TIC, except for maintenance chemotherapy. 3. Active brain metastases. Patients are eligible if brain metastases are properly treated and patients are neurologically stable. 4. Impairment of cardiac function. There are additional criteria that may prevent participation in this clinical study. The investigator will review these in detail until patients are included in this study. (BASEC)
Luogo dello studio
Ginevra, Losanna
(BASEC)
Sponsor
Mirati Therapeutics, Inc. PRA Switzerland AG
(BASEC)
Contatto per ulteriori informazioni sullo studio
Persona di contatto in Svizzera
Pr Solange Peters
+41 (0) 21-314-01-55
solange.peters@clutterchuv.chCentre Hospitalier Universitaire Vaudoi Lausanne
(BASEC)
Nome del comitato etico approvante (per studi multicentrici solo il comitato principale)
Commissione d'etica Vaud
(BASEC)
Data di approvazione del comitato etico
16.03.2021
(BASEC)
ID di studio ICTRP
EUCTR2019-001043-41 (ICTRP)
Titolo ufficiale (approvato dal comitato etico)
A Randomized Phase 3 Study of Sitravatinib in Combination with Nivolumab Versus Docetaxel in Patients with Advanced Non-Squamous Non-Small Cell Lung Cancer with Disease Progression On or After Platinum-Based Chemotherapy and Checkpoint Inhibitor Therapy (SAPPHIRE) (BASEC)
Titolo accademico
A Randomized Phase 3 Study of Sitravatinib in Combination with Nivolumab Versus Docetaxel in Patients with Advanced Non-Squamous Non-Small Cell Lung Cancer with Disease Progression On or After Platinum-Based Chemotherapy and Checkpoint Inhibitor Therapy (SAPPHIRE) (ICTRP)
Titolo pubblico
Phase 3 Study of Sitravatinib Plus Nivolumab vs Docetaxel in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer (ICTRP)
Malattie studiate
Non-Squamous Non-Small Cell Lung Cancer
MedDRA version: 20.0Level: LLTClassification code 10079440Term: Non-squamous non-small cell lung cancerSystem Organ Class: 100000004864;Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08] (ICTRP)
Intervento studiato
Product Name: Sitravatinib
Product Code: MGCD516
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Sitravatinib
Current Sponsor code: MGCD516 malate
Other descriptive name: Sitravatinib malate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 35-
Product Name: Sitravatinib
Product Code: MGCD516
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Sitravatinib
Current Sponsor code: MGCD516 malate
Other descriptive name: Sitravatinib malate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Trade Name: Opdivo
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Nivolumab
CAS Number: 946414-94-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: DOCETAXEL
CAS Number: 114977-28-5
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-
(ICTRP)
Tipo di studio
Interventional clinical trial of medicinal product (ICTRP)
Disegno dello studio
Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2 (ICTRP)
Criteri di inclusione/esclusione
Gender:
Female: yes
Male: yes
Inclusion criteria:
1. Diagnosis of Non-Squamous Non-Small Cell Lung Cancer
2. Receipt of at least one but not more than two prior treatment regimens in the advanced setting
3. Prior treatment with PD-1/PD-L1 checkpoint inhibitor therapy and platinum-based chemotherapy in combination or in sequence (i.e., platinum-based chemotheraphy followed by checkpoint inhibitor therapy)
4. Most recent treatment regimen must have included a checkpoint inhibitor therapy with radiographic disease progression on or after treatment
5. Candidate to receive docetaxel as second or third line therapy
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 266
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 266
(ICTRP)
Exclusion criteria:
1. Uncontrolled brain metastases
2. Tumors that have tested positive for EGFR, ROS1, ALK mutations, or ALK fusions
3. Unacceptable toxicity with prior checkpoint inhibitor therapy
4. Receipt of systemic anti-cancer therapy post checkpoint inhibitor therapy, other than maintenance chemotherapy
5. Impaired heart function
Endpoint primari e secondari
Main Objective: To compare Overall Survival (OS) in patients with non-squamous NSCLC who have experienced disease progression on or after platinum-based chemotherapy and CIT, treated with sitravatinib and nivolumab versus docetaxel.;Secondary Objective: - To evaluate the safety of sitravatinib in combination with nivolumab
in the study population.
- To evaluate the relative tolerability of sitravatinib and nivolumab
versus docetaxel.
- To evaluate secondary efficacy endpoints in the study population.
- To evaluate the pharmacokinetics (PK) of sitravatinib (MGCD516)
administered in combination with nivolumab.
- To evaluate health-related quality of life and lung cancer-specific
symptoms in the study population.;Primary end point(s): Overall Survival (OS);Timepoint(s) of evaluation of this end point: primary analysis, interim analysis, and end of study (ICTRP)
Secondary end point(s): 1. Safety characterized by type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events, laboratory abnormalities, and number of patients discontinuing study treatment due to an adverse event.
2. Secondary efficacy endpoints:
- Objective Response Rate (ORR) as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
-Duration of Response (DOR);
- Clinical Benefit Rate (CBR);
- Progression-Free Survival (PFS); and
- 1-Year Survival Rate.
3. Blood plasma concentrations of MGCD516.
4. Patient reported outcome (PROs):
- Lung Cancer Symptom Scale (LCSS); and
- European Quality of Life Five Dimensions Questionnaire (EQ-5D-5L).;Timepoint(s) of evaluation of this end point: primary analysis, interim analysis, and end of study (ICTRP)
Data di registrazione
16.06.2020 (ICTRP)
Inclusione del primo partecipante
11.12.2020 (ICTRP)
Sponsor secondari
non disponibile
Contatti aggiuntivi
Vanessa Tassell, tassellv@mirati.com, Mirati Therapeutics, Inc. (ICTRP)
ID secondari
516-005, NCT03906071, 2019-001043-41-FR (ICTRP)
Risultati-Dati individuali dei partecipanti
non disponibile
Ulteriori informazioni sullo studio
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-001043-41 (ICTRP)
Risultati dello studio
Riepilogo dei risultati
non disponibile
Link ai risultati nel registro primario
non disponibile