Efficacy and safety of rovalpituzumab tesirine in patients With DLL3-expressing, ≥ 3rd line small cell lung cancer: Results from the phase 2 TRINITY study.

8507 Background: Small cell lung cancer (SCLC) accounts for ~15% of lung cancer with no approved therapies in ≥ 3rd line (3L) patients (pts). In 3L pts, historical data demonstrate a median overall survival (mOS) of 4.7 mo and a best overall response of 18%; no historical data exist for objective response rate (ORR). Rovalpituzumab tesirine (Rova-T™) is an antibody-drug conjugate targeting Delta-like 3 protein (DLL3), an atypical Notch ligand that is highly expressed in SCLC but not normal tissue. A Ph1 study showed that Rova-T has antitumor activity in pts with recurrent SCLC and high DLL3 expression, and a manageable safety profile. Methods: TRINITY was an open-label, single-arm, Ph2 study of Rova-T in adult pts with DLL3-expressing SCLC (NCT02674568). Eligibility: ≥ 2 prior systemic regimens including ≥ 1 platinum-based regimen; ECOG 0-1; stable CNS disease. Pts received 0.3 mg/kg Rova-T intravenously on Day 1 of a 6-week cycle for 2 cycles. DLL3-high (hi) pts had ≥ 75% tumor cells positive by immunohistochemistry; DLL3-positive (pos) pts had ≥ 25%. Primary endpoints: confirmed ORR, overall survival (OS). Results: Interim analysis (6 Oct 17) included 199 pts, of which 64% were 3L. Common drug-related adverse events (AEs) were fatigue (32%), photosensitivity (31%), pleural effusion (26%), peripheral edema (26%), thrombocytopenia (23%). Drug-related Grade 3/4 AEs were thrombocytopenia (15%), photosensitivity (7%), pleural effusion (7%), fatigue (5%). In DLL3-hi 3L pts, median progression-free survival (mPFS) = 4.1 mo, mOS = 6.7 mo. Conclusions: Rova-T demonstrated antitumor activity and a favorable benefit:risk profile in ≥ 3L SCLC pts, with clinically meaningful mOS and mPFS. Updated analysis will be shown at presentation. Clinical trial information: NCT02674568.n (%) DLL3-hi DLL3-pos 3L N = 85 ≥ 3L N = 140 3L N = 103 ≥ 3L N = 165 Best Overall Response IA 27 (32) 39 (28) 31 (30) 45 (27) IRC 24 (28) 32 (23) 27 (26) 36 (22) ORR IA 20 (24) 30 (21) 23 (22) 35 (21) IRC 15 (18) 20 (14) 17 (17) 23 (14) Clinical Benefit Rate* IA 59 (69) 100 (71) 67 (65) 111 (67) IRC 60 (71) 105 (75) 67 (65) 117 (71) IA, investigator assessment; IRC, independent radiology committee*complete response + partial response + stable disease