Frontline Brentuximab Vedotin and CHP (A+CHP) in Patients (pts) with Peripheral T-cell Lymphoma with Less Than 10% CD30 Expression: Results from the Phase 2 SGN35-032 Study.

7069 Background: Brentuximab vedotin (BV), an anti-CD30 antibody-drug conjugate, combined with cyclophosphamide, doxorubicin, and prednisone (A+CHP) was evaluated in the phase 3 ECHELON-2 trial in pts with anaplastic large cell lymphoma (ALCL) and other peripheral T-cell lymphoma (PTCL) types with ≥10% CD30 expression. Compared to conventional frontline therapy, pts treated with A+CHP had a 30% risk reduction in progression-free survival (PFS) (stratified HR=0.70 [95% CI: 0.53, 0.91], P=0.0077) and a survival benefit (HR=0.72 [95% CI: 0.53, 0.99], P=0.0424) (Horwitz 2022). Since no correlation between CD30 expression and duration of response (DOR) was found, it was hypothesized that frontline A+CHP may also be active in pts with non-sALCL PTCL with <10% CD30 expression. Methods: SGN35-032 (NCT04569032; EudraCT 2020-002336-74) is an ongoing phase 2 study. Pts with newly diagnosed non-sALCL PTCL with <10% CD30 expression (by local assessment) are enrolled. Pts are assigned to CD30 <1% or CD30 1% to <10% cohorts. All pts receive 21-day cycles of A+CHP (BV 1.8 mg/kg, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2 by IV infusion, and prednisone 100 mg po qd on Days 1-5) for up to 6-8 cycles. The primary endpoint, overall response rate (ORR), is assessed by blinded independent central review (BICR) per Cheson 2007. Secondary endpoints are complete response (CR) rate, PFS, overall survival (OS), DOR, ORR per BICR using modified Lugano, and safety. Results: Seventy pts received ≥1 dose of study drug as of June 30, 2023. Median age was 63.5 years, 57% were male, and 90% had ECOG ≤1. Most had stage IV disease (63%) and were in the CD30 1% to <10% cohort per local CD30 (55%). Median treatment duration was 18 weeks (range, 0-24 weeks). Per BICR, ORR was 77% (95% CI: 65.3%, 86.7%), including 65% (95% CI: 52.4%, 76.5%) with CR among the 66 efficacy evaluable (EE) pts. ORR and CR rate per BICR are listed by cohort in the Table. Grade ≥3 treatment-emergent adverse events (TEAEs) were experienced by 43 pts (61%), most commonly neutropenia (20%), febrile neutropenia (17%), and anemia (10%). Six pts (9%) discontinued treatment due to TEAEs. Nineteen pts (27%) had BV-related serious TEAEs. There were 2 (3%) treatment-related deaths: 1 pt died of decreased appetite and 1 pt died of general physical health deterioration. Conclusions: In pts with non-sALCL PTCL with <10% CD30 expression, A+CHP as frontline therapy appears effective and has a safety profile consistent with label. Clinical trial information: NCT04569032 . [Table: see text]