Starlyte phase II study of coltuximab ravtansine (CoR, SAR3419) single agent: clinical activity and safety in patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL; NCT01472887)

Background: CoR is an anti-CD19 antibody maytansinoid conjugate. CD19 is expressed in the majority of B cell lymphomas. Phase I program showed clinical activity in pts with both indolent and aggressive lymphomas. Methods: Pts withCD19+ R/R DLBCL after at least one standard treatment including rituximab and not candidate for transplantation were eligible. Primary refractory pts were excluded. Biopsy was required at baseline. CoR 55 mg/m² was administered weekly for 4 weeks then bi-weekly until disease progression or other study discontinuation criteria. The primary objective was to demonstrate an overall response rate (ORR) of at least 20% following Cheson 2007 criteria. Tumor assessments were done every 12 weeks. Secondary objectives were: safety, pharmacokinetics (PK), duration of response (DOR), progression free and overall survival (PFS, OS). Assessment of correlation between biomarkers (BM) status and disease outcome was an exploratory objective. Results: 41 pts were evaluable. Median age was 71 (39:85), 53.7% were male; 92.7% had ECOG performance status 0-1. 31.7% had received ≥ 3 prior regimens for DLBCL. The ORR was 43.9% (90% CI: 30.6% to 57.9%, p-value<0.0001) including 5 complete responses (12.2%). DOR, OS and PFS data are not mature (11 pts ongoing). The most common (>10%) all grades (gr) non-hematologic treatment-emergent adverse events (TEAEs) were nausea (23.0%), diarrhea (19.7%), fatigue and cough (18.0%), vomiting and decrease appetite (13.1%), asthenia, abdominal and back pain (11.5%). TEAEs led to treatment discontinuation in 4 pts. Only gr 1-2 eye disorders were reported, including 1 pt with unrelated gr 2 keratitis. Peripheral neuropathies were observed in 5 pts, all were gr 1-2. Hematological toxicity was moderate, with gr 3-4 neutropenia, thrombocytopenia and anemia in 26.4%, 9.9% and 6.6% pts respectively. PK assessment and investigations on BM expression are ongoing. Conclusions: CoR as single agent demonstrated significant activity in R/R DLBCL pts and reached its primary endpoint for ORR, with acceptable safety profile. Trial funded by Sanofi. Clinical trial information: NCT01472887.