P1130: FRONTLINE BRENTUXIMAB VEDOTIN AND CHP (A+CHP) IN PATIENTS WITH PERIPHERAL T-CELL LYMPHOMA WITH LESS THAN 10% CD30 EXPRESSION: INITIAL SAFETY AND EFFICACY RESULTS FROM THE PHASE 2 STUDY SGN35-032

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: In ECHELON-2, brentuximab vedotin (BV), a CD30-directed ADC, combined with cyclophosphamide, doxorubicin, and prednisone (A+CHP) enrolled patients (pts) with ALCL and other types of PTCL with ≥10% CD30 expression. Patients treated with A+CHP had a 29% reduction in the risk of a PFS event (stratified HR=0.70 [95% CI: 0.53, 0.91], P=0.0770) and a survival benefit (HR=0.72 [95% CI 0.53, 0.99], P=0.0424) compared with conventional frontline therapy (Advani 2019). In pts with non-ALCL PTCL treated with A+CHP there was no apparent correlation between CD30 expression level and the likelihood of response (Horwitz 2022). It is hypothesized that A+CHP will demonstrate efficacy in pts with non-ALCL PTCL with <10% CD30 expression both due to this lack of correlation and because clinical responses to BV monotherapy can occur in pts with low and undetectable CD30 expression (Jagadeesh 2019). Aims: To present initial efficacy and safety results from SGN35-032 (NCT04569032; EudraCT 2020-002336-74), a study of A+CHP for pts with previously untreated PTCL with <10% CD30 expression. Methods: SGN35-032 is a dual-cohort, open-label, multicenter, phase 2 trial. This study enrolled pts with non-ALCL PTCL with CD30 expression <10% by local CD30 staining; for purposes of this study, patients were stratified as CD30-negative (expression <1%) or CD30-low (expression ≥1% to <10%). Pts received 21-day cycles of A+CHP. The primary endpoint is objective response rate (ORR) per blinded independent central review (BICR) using the Revised Response Criteria for Malignant Lymphoma (Cheson 2007). Key secondary endpoints include complete response (CR) rate, progression-free survival (PFS), and duration of response (DOR) assessed by BICR per Cheson 2007 and modified Lugano criteria. However, initial efficacy results are based on investigator assessment at data cutoff on 13Jan2023. Results: A total of 55 pts were enrolled and 55 received at least 1 dose of study treatment as of data cutoff. The median age was 64.0 years (range: 35, 80). 23 pts were CD30 negative and 32 pts were CD30 low by local staining. Disease subtypes included PTCL-NOS (n=24), AITL (n=17), and FTCL (n=5). Pts received a median of 6 cycles of A+CHP (range: 1, 8) over a median of 18 weeks (range: 0, 24). Of the 55 pts treated, 45 had at least one post-baseline response assessment or discontinued treatment; efficacy results are limited to this population. Safety results are reported for all treated pts. CD30-negative pts (n=18) had an ORR of 83% (95% CI: 58.6, 96.4) and CR rate of 56% (95% CI: 30.8, 78.5). CD30-low pts (n=27) had an ORR of 74% (95% CI: 53.7, 88.9) and CR rate of 59% (95% CI: 38.8, 77.6). DOR and PFS results were premature with limited follow-up duration at time of data cutoff. Diarrhea, nausea, and peripheral sensory neuropathy were the most frequently reported treatment-related treatment-emergent adverse events (TEAEs) (27%, 24%, and 22% of pts, respectively). 3 pts (5%) discontinued study treatment due to a TEAE. 29 pts (53%) experienced a Grade ≥3 TEAE; most commonly febrile neutropenia (18%). 20 pts (36%) experienced treatment-emergent serious adverse events. 1 pt (2%) had a treatment-related fatal event of general physical health deterioration. Summary/Conclusion: Initial findings show that A+CHP is effective for pts with PTCL regardless of CD30 expression by local testing. Safety results are consistent with previous data from ECHELON-2 and no new safety signals were observed. This study is ongoing and updated results will be presented in the future. Keywords: Peripheral T-cell lymphoma, Targeted therapy, T cell lymphoma