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)
Zusammenfassung der Studie
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)
Untersuchte Intervention
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)
Untersuchte Krankheit(en)
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)
Ausschlusskriterien
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)
Studienstandort
Genf, Lausanne
(BASEC)
Sponsor
Mirati Therapeutics, Inc. PRA Switzerland AG
(BASEC)
Kontakt für weitere Auskünfte zur Studie
Kontaktperson Schweiz
Pr Solange Peters
+41 (0) 21-314-01-55
solange.peters@clutterchuv.chCentre Hospitalier Universitaire Vaudoi Lausanne
(BASEC)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Waadt
(BASEC)
Datum der Bewilligung durch die Ethikkommission
16.03.2021
(BASEC)
ICTRP Studien-ID
EUCTR2019-001043-41 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
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)
Wissenschaftlicher Titel
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)
Öffentlicher Titel
Phase 3 Study of Sitravatinib Plus Nivolumab vs Docetaxel in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer (ICTRP)
Untersuchte Krankheit(en)
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)
Untersuchte Intervention
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)
Studientyp
Interventional clinical trial of medicinal product (ICTRP)
Studiendesign
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)
Ein-/Ausschlusskriterien
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
Primäre und sekundäre Endpunkte
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)
Registrierungsdatum
16.06.2020 (ICTRP)
Einschluss des ersten Teilnehmers
11.12.2020 (ICTRP)
Sekundäre Sponsoren
nicht verfügbar
Weitere Kontakte
Vanessa Tassell, tassellv@mirati.com, Mirati Therapeutics, Inc. (ICTRP)
Sekundäre IDs
516-005, NCT03906071, 2019-001043-41-FR (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar
Weitere Informationen zur Studie
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-001043-41 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
nicht verfügbar
Link zu den Ergebnissen im Primärregister
nicht verfügbar