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OA02 - Novel Therapies in ROS1, HER2 and EGFR (ID 893)
- Event: WCLC 2018
- Type: Oral Abstract Session
- Track: Targeted Therapy
- Presentations: 1
- Coordinates: 9/24/2018, 10:30 - 12:00, Room 105
OA02.01 - Efficacy and Safety of Entrectinib in Locally Advanced or Metastatic ROS1 Fusion-Positive Non-Small Cell Lung Cancer (NSCLC) (ID 13903)
10:30 - 10:40 | Author(s): Todd Riehl
Entrectinib is a central nervous system (CNS) active, potent, and selective inhibitor of ROS1, TRKA/B/C and ALK. Entrectinib is more potent against ROS1 than crizotinib, the only agent currently approved for the treatment of ROS1-positive NSCLC. Interim data demonstrated that entrectinib was tolerable and achieved high objective response rates (ORR) in patients with ROS1-positive, ROS1 inhibitor-naive NSCLC, including patients with baseline CNS disease (Ahn MJ WCLC 2017).a9ded1e5ce5d75814730bb4caaf49419 Method
Phase 1/2 studies of entrectinib (ALKA, STARTRK-1, STARTRK-2; EudraCT 2012-000148-88; NCT02097810; NCT02568267) enrolled patients with locally advanced or metastatic solid tumors. The safety-evaluable population included patients who received ≥1 dose of entrectinib. The integrated efficacy analysis included ROS1-positive NSCLC patients enrolled based on identification of ROS1 fusions via nucleic acid-based diagnostic platforms. Safety was assessed by monitoring adverse events (AEs), laboratory tests, and physical examination. Tumor assessments were performed at the end of cycle 1 and every 8 weeks thereafter. All scans were submitted for blinded independent central review (BICR) using RECISTv1.1. Primary endpoints were ORR and duration of response (DOR) by BICR. Key secondary objectives were progression-free survival (PFS), overall survival (OS), and safety. Additional endpoints evaluated in patients with baseline CNS disease were intracranial ORR (defined as complete or partial responses in patients with baseline CNS lesions per BICR using RECISTv1.1), intracranial DOR, and PFS. For intracranial assessments, the CNS subgroup was derived per BICR; for systemic analyses, the CNS subgroup was derived per investigator.4c3880bb027f159e801041b1021e88e8 Result
There were 53 efficacy-evaluable patients with treatment-naïve, ROS1-positive NSCLC. BICR ORR was 77.4% (95% CI 63.8–87.7) with complete responses in three patients (5.7%); median BICR DOR was 24.6 months (95% CI 11.4–34.8). Per baseline CNS status (as determined by investigator), median BICR PFS was 26.3 months (95% CI 15.7–36.6) and 13.6 months (95% CI 4.5–NR) for patients without (n=30) and with CNS disease (n=23), respectively. Intracranial ORR was 55.0% (95% CI 31.5–76.9) and median intracranial DOR was 12.9 months (95% CI 5.6–not reached [NR]) in patients with baseline CNS disease per BICR (n=20). In the overall safety-evaluable population (n=355), most treatment-related AEs were grade 1–2. Few patients required dose reduction (27.3%) or discontinued treatment (3.9%) due to treatment-related AEs.8eea62084ca7e541d918e823422bd82e Conclusion
Entrectinib was tolerable with a manageable safety profile, and showed clinically meaningful, deep and durable systemic responses in ROS1-positive NSCLC. Clinically meaningful intracranial activity was also demonstrated in patients with baseline CNS disease.6f8b794f3246b0c1e1780bb4d4d5dc53
Study Sponsor: Ignyta, Inc., a wholly owned subsidiary of F. Hoffmann-La Roche Ltd.
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