Frontline brentuximab vedotin (BV) and CHP in patients (pts) with peripheral T-cell lymphoma (PTCL) with <10% CD30 expression: Primary analysis results from the phase 2 SGN35-032 study.

Abstract

7077 Background: BV, an antibody-drug conjugate targeting CD30, has shown single-agent activity in lymphomas with low CD30 expression. The combination of BV plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) was effective in pts with PTCL with CD30 ≥10%. We report primary analysis results of frontline A+CHP in pts with non-systemic anaplastic large cell lymphoma (non-sALCL) PTCL with CD30 <10%. Methods: SGN35-032 (NCT04569032) is an open-label, multicenter, phase 2 study. Pts received 21-day cycles of A+CHP (BV 1.8 mg/kg, cyclophosphamide 750 mg/m 2 , and doxorubicin 50 mg/m 2 by IV infusion on day 1 of each cycle and prednisone 100 mg by mouth daily [days 1-5]) up to 6-8 cycles. The primary endpoint, objective response rate (ORR), was assessed by blinded independent central review per Cheson 2007. Secondary endpoints included safety and complete response (CR) rate, PFS, OS, and duration of response (DOR). Efficacy endpoints are reported per central CD30 assessment unless otherwise noted. A genAI tool (12/13/24; Pfizer; GPT-4o) developed the 1st draft; authors assume content responsibility. Results: As of Jul 22, 2024, 82 pts received ≥1 dose of A+CHP, including 34 in the CD30 <1% cohort and 48 in the CD30 1% to <10% cohort per local CD30 assessment. At data cutoff, all pts were off study treatment. Overall median age was 63.5 y; most pts were male (56%), were White (77%), had an IPI score of 2-3 (66%), and had an ECOG PS ≤1 (90%). The most common (≥10%) disease subtypes were PTCL-not otherwise specified (45%), angioimmunoblastic T-cell lymphoma (32%), and nodal PTCL with T-follicular helper phenotype (10%). Overall median duration of treatment was 18.0 w (range, 3-24). The ORR at treatment completion was 77% (95% CI, 66.2-85.4) with a CR rate of 63% (95% CI, 52.0-73.8). Median (95% CI) PFS and OS were 12.7 mo (9.0-not estimable [NE]) and not reached (NR; 24.4-NE). Median (95% CI) DOR was 15.9 mo (8.3-NE), but NR in either cohort. Other efficacy parameters per cohort are listed in the table. Most pts (95%) had a treatment-emergent adverse event (TEAE), with 59% having a grade ≥3 TEAE. The most common (≥10%) overall grade ≥3 TEAEs were neutropenia (18%), febrile neutropenia (17%), and anemia (10%). Treatment-related grade 5 TEAEs were reported in 2 pts (2%); 19 pts (23%) reported a BV-related serious TEAE. Conclusions: As a frontline therapy, A+CHP demonstrated clinically meaningful efficacy in pts with non-sALCL PTCL regardless of CD30 expression, with a safety profile consistent with the label. Clinical trial information: NCT04569032 . CD30 <1% CD30 1% to <10% Per local CD30 n=34 n=48 ORR (95% CI), % 74 (55.6-87.1) 79 (65.0-89.5) CR rate (95% CI), % 56 (37.9-72.8) 69 (53.7-81.3) Per central CD30 n=23 n=31 ORR (95% CI), % 61 (38.5-80.3) 81 (62.5-92.5) CR rate (95% CI), % 52 (30.6-73.2) 71 (52.0-85.8) PFS, median (95% CI), mo 10.9 (5.0-NE) NR (8.5-NE) OS, median (95% CI), mo NR (11.1-NE) NR (21.3-NE)