Date trial registered
Aug 10, 2017
Incorporation of the first participant
Nov 24, 2017
Recruitment status
Authorised-recruitment may be ongoing or finished
Academic title
(Data source: WHO)
A PHASE II/III MULTICENTER STUDY EVALUATING THE EFFICACY AND SAFETY OF MULTIPLE TARGETED THERAPIES AS TREATMENTS FOR PATIENTS WITH ADVANCED OR METASTATIC NON SMALL CELL LUNG CANCER (NSCLC) HARBORING ACTIONABLE SOMATIC MUTATIONS DETECTED IN BLOOD (B-FAST: BLOOD-FIRST ASSAY SCREENING TRIAL)
Type of trial
(Data source: WHO)
Interventional clinical trial of medicinal product
Design of the trial
(Data source: WHO)
Controlled: no
Randomised: yes
Open: yes
Single blind: no
Double blind: no
Parallel group: no
Cross over: no
Other: no
If controlled, specify comparator, Other Medicinial Product: no
Placebo: no
Other: no
Number of treatment arms in the trial: 5
Phase
(Data source: WHO)
Human pharmacology (Phase I): noTherapeutic exploratory (Phase II): yesTherapeutic confirmatory - (Phase III): yesTherapeutic use (Phase IV): no
Primary end point
(Data source: WHO)
Main Objective: • To evaluate the efficacy of multiple therapies in patients with NSCLC selected according to results from the FoundationOne Liquid Companion Diagnostic (F1LCDx): alectinib (ALK+; RET+); entrectinib (ROS1+); atezolizumab (atezo) + cobimetinib (cobi) + vemurafenib (vem) (BRAF V600+); atezo + bevacizumab (bev) + carboplatin + pemetrexed (EGFR exon 20+)
• To evaluate the efficacy of atezo compared with platinum-based chemotherapy in treatment-naive patients with inoperable Stage IIIB or Stage IV NSCLC in patients who are blood tumor mutational burden positive according to F1LCDx (Cohort C)
;Secondary Objective: To evaluate:
• The safety and tolerability of alectinib, atezo, entrectinib, atezo + cobi + vem, atezo + bev + carboplatin + pemetrexed (Cohorts A, B, C, D E, F)
• The pharmacokinetic (PK) characteristics of alectinib in RET+ patients (Cohort B), entrectinib in ROS1+ patients (Cohort D), atezo in BRAF V600+ patients (Cohort E) and in patients with EGFR exon 20+ advanced or metastatic NSCLC (Cohort F)
• The impact of study treatment on patient-reported outcome (PROs)
• The efficacy of entrectinib in patients with ROS1+ advanced or metastatic NSCLC, atezo +cobi + vem in patients with BRAF V600+, and atezo + bev + carboplatin + pemetrexed in patients with EGFR exon 20+ advanced or metastatic NSCLC, as determined by the F1LCDx assay
• Prognostic effect and pharmacodynamics of exploratory biomarkers in blood, and their association with disease status, mechanisms of resistance, and/or response to alectinib (Cohorts A, B), atezo (Cohort C, E, and F), entrectinib (Cohort D)
;Primary end point(s): 1. Investigator-assessed ORR based on confirmed objective response (Cohorts A, B, D, and F)
2. Investigator-assessed PFS according to RECIST v1.1 (Cohort C) in bTMB the primary population of patients with a bTMB level equal to or greater than the higher validated cutoff (PP1)
3. Investigator-assessed 12-month time in response (TIR) per RECIST v1.1 (Cohort E)
;Timepoint(s) of evaluation of this end point: 1-3. Up to 6 years
Secundary end point
(Data source: WHO)
Secondary end point(s): 1. Investigator-assessed DOR, CBR, and PFS per RECIST v1.1 (Cohorts A, B, and D)
2. IRF-assessed ORR, DOR, CBR, and PFS per RECIST v1.1 (Cohorts A, B, and D)
3. IRF-assessed PFS, ORR, and DOR according to RECIST v1.1 (Cohort C and F)
4. Investigator-assessed ORR, and DOR according to RECIST v1.1 (Cohort C)
5. Investigator- and IRF-assessed time to CNS progression according to RECIST v1.1 (Cohort D)
6. Investigator-assessed intracranial tumor response rate by RECIST 1.1 in patients with measurable CNS disease at baseline (Cohort D)
7. OS (Cohorts A, B, D, E, and F)
8. Investigator-assessed PFS rates at 6-month and 1-year landmark timepoints (Cohort C)
9. Incidence, type, and severity of adverse events (based on the NCI CTCAE v4.0), including SAEs and AEs of special interest (Cohorts A, B, C, D, E, and F)
10. Changes in vital signs, physical findings, and clinical laboratory results during and following administration of protocol-specified IMPs (Cohorts A, B, D, E, and F)
11. DLTs, if any, associated with alectinib at escalating doses in RET+ patients (Cohort B)
12. PK parameters of alectinib in RET+ patients (Cohort B)
13. Population PK analysis for entrectinib (Cohort D)
14. Proportion of patients who improved compared with baseline in patient-reported lung cancer symptoms of cough, dyspnea, and chest pain and TTD as measured by SILC (Cohorts A, B, C, D, E, and F)
15. Proportion of patients presenting with measurable CNS disease at baseline who improve compared with baseline in patient-reported cognitive function, fatigue, health-related quality of life (HRQoL), headache, and vision disorder per the corresponding scales of the EORTC QLQ-C30 and BN20 (Cohort D)
16. Mean change from baseline in HRQoL, patient functioning, and symptoms as measured by the EORTC
QLQ-C30 (Cohorts A, B, C, D, E, and F)
17. Health status as assessed by the EQ-5D-5L questionnaire (Cohorts A, B, C, D, E, and F)
18. Relationship between circulating biomarkers related to alectinib exposure and efficacy (Cohorts A and B), to atezolizumab efficacy (Cohort C) to entrectinib efficacy (Cohort D), atezo + cobi + vem efficacy (Cohort E), and atezo + bev + carboplatin + pemetrexed efficacy (Cohort F)
19. OS in bTMB PP1 (Cohort C)
20. Investigator-assessed PFS according to RECIST v1.1 in bTMB the secondary population of all patients who are bTMB-positive, which is the intent-to-treat (ITT) population in this cohort (PP2) [Cohort C]
21. OS in bTMB PP2 (Cohort C)
22. Investigator and IRF-assessed -assessed ORR, DOR, and PFS per RECIST v1.1 (Cohort E)
23. Investigator-assessed DOR and PFS per RECIST v1.1 (Cohort F)
24. 9-month TIR (Cohort E)
25. 12-month TIR (Cohort E)
26. Serum concentration of atezo at specified timepoints (Cohort E and F)
27. Presence of ADAs against atezo during the study relative to the presence of ADAs at baseline (Cohort E and F);Timepoint(s) of evaluation of this end point: 1-7. Up to 6 years
8. At 6 month and 1 year
9-10. Up to 6 years
11. From Day 1 (D1) to D28 of Cycle 1 (C1)
12. Dose-Finding Phase: C1D1, C1D8, C2D1, C3D1, C4D1
Expansion Phase: C1D1, C2D1, C3D1, C4D1
13. C1D1, C3D1, C5D1
14- 17. At 3 and 6 months following disease progression up to 6 years
18-23. Up to 6 years
24. 9 months
25. 12 months
26-27. C1D1, C2D1, C3D1, C4D1, C8D1, C12D1, C16D1 and at treatment discontinuation visit
Contact information
(Data source: WHO)
F. Hoffmann-La Roche Ltd