Brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine for early‐stage classical Hodgkin Lymphoma: Updated results from an ongoing phase 2 study (SGN35‐027 Part C)

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Introduction: Brentuximab vedotin (BV) and nivolumab are well tolerated, active treatments for patients (pts) with classical Hodgkin lymphoma (cHL) (Advani 2021; Yasenchak 2020). Herein, we present updated efficacy and safety results from an ongoing phase 2 study of a novel combination of BV + nivolumab with doxorubicin and dacarbazine among pts with early-stage cHL (SGN35-027 Part C). Methods: SGN35-027 (NCT03646123) Part C enrolled pts with Ann Arbor stage I or II cHL without bulky disease (single node or nodal mass with a diameter <10 cm on computed tomography imaging). Pts received 4 cycles of AN + AD (BV 1.2 mg/kg [A], nivolumab 240 mg [N], doxorubicin 25 mg/m2 [A], and dacarbazine 375 mg/m2 [D] administered intravenously on Days 1 and 15 of each 28-day cycle). Radiation was not included. The primary endpoint was the complete response (CR) rate at end of treatment (EOT). Secondary endpoints included safety and tolerability, objective response rate (ORR), duration of response, duration of complete response, and progression-free survival. Results: Part C enrolled 156 pts and 154 pts received at least 1 dose of study treatment. The majority of pts were white (84%), <65 years old (92%), and female (55%). Median age was 31.0 years (range: 18, 77). Pts had stage I (11%) or II (89%) cHL without bulky disease. All data are based on a cutoff of 28 November 2022. The Efficacy Evaluable population (completed an EOT response assessment) had 147 pts. A 92% CR rate and 98% ORR were observed among these pts (see table for efficacy data). The planned 4 treatment cycles were completed by 94% of pts. Three percent of pts discontinued treatment (all study drugs) because of treatment-emergent adverse events (TEAEs). Thirty-three percent and 3% of pts experienced Grade ≥3 treatment-related TEAEs and Grade ≥3 treatment-related peripheral sensory neuropathy, respectively. Treatment-emergent immune-mediated adverse events (IMAEs) were experienced by 21% of pts, and 6% of pts experienced Grade ≥3 treatment-emergent IMAEs. Treatment-related serious TEAEs were experienced by 13% of pts. No deaths occurred. Part C is ongoing with 85% of pts in long-term follow-up. Conclusions: Updated results indicate that AN + AD has promising efficacy and an acceptable safety profile in pts with early-stage cHL without bulky disease. No new safety signals were observed. The research was funded by: Seagen Inc. with support from Bristol-Myers Squibb Keywords: Combination Therapies, Hodgkin lymphoma, Immunotherapy Conflicts of interests pertinent to the abstract. J. S. Abramson Consultant or advisory role: Allogene, Astra-Zeneca, BeiGene, Bluebird Bio, Bristol-Myers Squibb, C4 Therapeutics, Celgene, Century Therapeutics, Epizyme, Genentech, Regeneron, Genmab, Incyte, Karyopharm Kite Pharma, Kymera, MorphoSys, Mustang Bio, Ono Pharma Research funding: Bristol-Myers Squibb, SeaGen D. Straus Consultant or advisory role: Seagen, Takeda Research funding: Seagen N. Bartlett Consultant or advisory role: ADC Therapeutics, Roche/Genentech, Seagen Research funding: ADC Therapeutics, Autolus, Bristol-Myers Squibb, Celgene, Forty Seven, Genentech, Janssen, Kite, Merck, Millennium, Pharmacyclics, Seagen J. M. Burke Consultant or advisory role: Abbvie, Adaptive Bio, AstraZeneca, BeiGene, Bristol-Myers Squibb, Epizyme, Kura, Kymera, MorphoSys, Roche/Genentech, Seagen, Verastem Research funding: BeiGene, Seagen E. Domingo-Domenech Consultant or advisory role: Takeda Other remuneration: Takeda Y. Linhares Consultant or advisory role: Abbvie, ADC, Alexion, AstraZeneca, BeiGene, Celgene, Genentech, GSK, Incyte, Janssen, Kyowa, Novartis, Seagen Research funding: BeiGene, Seagen Other remuneration: Kyowa Kirin, Curio Science Workshop Participation and Moderation R. Ramchandren Consultant or advisory role: Bristol-Myers Squibb, Merck, Pharmacyclics, Seagen Research funding: Curis, Merck, Pharmacyclics, Seagen, Trillium M. Gandhi Honoraria: GlaxoSmithKline, Karyopharm, TG Therapeutics W. Jurczak Employment or leadership position: Abbvie, Astra Zeneca, BeiGene, Janssen, Lilly, Merck, Morphosys, Roche, Seagen, Takeda Consultant or advisory role: Abbvie, Astra Zeneca, BeiGene, Lilly, Roche, Takeda A. Re Consultant or advisory role: Takeda, Incyte, Servier, Italfarmaco L. Ho Employment or leadership position: Seagen Stock ownership: Seagen Educational grants: Seagen W. Guo Employment or leadership position: Seagen Stock ownership: Seagen S. Jain Employment or leadership position: Seagen Stock ownership: Seagen C. Yasenchak Research funding: Seagen H. J. Lee Consultant or advisory role: Century Therapeutics, Bristol-Myers Squibb, Deloitte, Guidepoint Global, Honoraria: Aptitude Health, Cancer Experts, Curio Science, Korean Society of Cardiology, Olson Research Research funding: Bristol-Myers Squibb, Celgene, Octernal Therapeutics, Seagen, Takeda, Pharmacyclics

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