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

Background Small cell lung cancer (SCLC) accounts for ~ 15% of lung cancer with no approved therapies in ≥ 3rd line (3 L) patients (pts). In 3 L 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 3 L. 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 3 L 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 ≥ 3 L SCLC pts, with clinically meaningful mOS and mPFS. Updated analysis from ASCO will be shown at presentation. Clinical trial information: NCT02 674 568