Efficacy and Safety of Retreatment with Brentuximab Vedotin in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma or CD30-Expressing Peripheral T Cell Lymphoma

Introduction Brentuximab vedotin (BV) is approved for the treatment of adult patients (pts) with classical Hodgkin lymphoma (cHL), systemic anaplastic large cell lymphomas (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL). BV has been evaluated in combination with doxorubicin, vinblastine, and dacarbazine (A+AVD) in adult pts with advanced stage cHL in ECHELON-1 (Ansell S, 2022) and in combination with cyclophosphamide, doxorubicin, and prednisone (A+CHP) in pts with sALCL, PTCL-not otherwise specified (NOS), and angioimmunoblastic T-cell lymphoma (AITL) in ECHELON-2 (Horwitz S, 2022), demonstrating BV is well tolerated with a favorable efficacy profile in the first-line setting. Moreover, BV is approved as monotherapy for treatment of adults with cHL at high risk of relapse as consolidation therapy post autologous stem cell transplant, as well as in relapsed or refractory (r/r) sALCL. BV has also been studied in r/r cHL after auto-stem cell transplant (Younes A, 2012) and retreatment setting (Trümper L, 2020), with favorable efficacy. CD30 expression persists after BV treatment and SGN35-006 demonstrated that BV monotherapy is an effective retreatment option in pts with r/r cHL or sALCL who previously achieved an objective response with BV monotherapy (Bartlett N, 2014). Herein, we present efficacy and safety results from a phase 2 study, where BV was evaluated in pts with r/r cHL or CD30-expressing PTCL who previously received BV either alone or in combination.

Methods SGN35-028 (NCT03947255) is a multicentered, single arm, phase 2 clinical trial that enrolled adult pts with r/r cHL and sALCL or other CD30-expressing PTCL who were previously treated with a BV-containing regimen at least 6 months prior that had evidence of an objective response, and subsequently experienced disease progression or relapse after discontinuing treatment. Pts were treated with BV 1.2 or 1.8 mg/kg intravenously every 3 weeks until disease progression or unacceptable toxicity. The primary endpoints were objective response rate (ORR) and the safety and tolerability of BV retreatment.

Results Of the 12 pts enrolled, 11 received at least 1 dose of study treatment including 5 pts with cHL and 6 pts with PTCL (4 pts with sALCL, 1 pt with PTCL-NOS, 1 pt with AITL). Both pts with non-ALCL PTCL had CD30 expression on 1% of tumor cells. Of the 11 pts that received at least 1 dose of study treatment, most were Black or African American (55%), not of Hispanic, Latino, or Spanish origin (91%), and <65 years old (73%). Pts received a median of 8 doses of BV (range: 1, 16) over a median of 25 weeks (range: 3, 55), 3 pts (27%) had dose reductions. Three pts were still on treatment as of data cutoff date.

For pts with cHL, median time from initial diagnosis to first dose was 76.2 months (range: 34, 162), 2 pts achieved complete response (CR) and 3 pts partial response (PR) on prior BV therapy, median time from completion of last BV therapy to first dose was 28.2 months, and median age was 31 years (range: 28, 55). The ORR per investigator assessment was 60% (95% CI: 14.7, 94.7) with 1 pt achieving CR.

For pts with PTCL, median time from initial diagnosis to first dose was 31.2 months (range: 23, 138), 5 pts achieved CR and 1 pt PR on prior BV therapy, median time from completion of last BV therapy to first dose was 20.1 months, and median age was 63 years (range: 35, 77). The ORR per investigator assessment was 83% (95% CI: 35.9, 99.6) with 4 pts achieving CR. The 4 pts with sALCL had an ORR of 100% with a CR rate of 75%.

Eight pts discontinued study treatment, 4 pts discontinued treatment due to disease progression, 2 pts due to investigator decision, and 2 pts due to treatment emergent adverse events (TEAEs), both with peripheral sensory neuropathy. Thirty-six percent of pts experienced ≥ Grade 3 treatment-related TEAEs, 2 (18%) each for neutropenia and peripheral sensory neuropathy and 1 (9%) each for amylase increased, fatigue, malaise, and nausea. One pt experienced a Grade 5 adverse event of decreased appetite related to progressive PTCL disease that was not treatment related.

Conclusions Preliminary results from this study show BV is a viable retreatment option for adults with r/r cHL, sALCL, and PTCL. Moreover, safety results were consistent with the known safety profile and no new safety signals were observed. This study is ongoing, updated efficacy and safety results will be presented at the meeting.

Ahmed:Myeloid Therapeutics: Consultancy; Servier: Membership on an entity's Board of Directors or advisory committees; Xencor: Research Funding; Tessa Therapeutics: Consultancy, Research Funding; Seagen: Research Funding; Merck: Research Funding; Chimagen: Consultancy, Research Funding. Liu:Seagen: Current Employment, Current equity holder in publicly-traded company. Knowles:Seagen: Current Employment, Current equity holder in publicly-traded company.