Volume 7, Issue S3 e5881312
Poster
Open Access

P1064: BRENTUXIMAB VEDOTIN, NIVOLUMAB, DOXORUBICIN, AND DACARBAZINE FOR ADVANCED STAGE CLASSICAL HODGKIN LYMPHOMA: UPDATED EFFICACY AND SAFETY RESULTS FROM THE SINGLE ARM PHASE 2 STUDY

Chris Yasenchak

Chris Yasenchak

Williamette Valley Cancer Institute and Research Center, Eugene, OR, United States

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Ian W. Flinn

Ian W. Flinn

Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN, United States

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Jason Melear

Jason Melear

US Oncology Research, The Woodlands, TX, United States

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Rod Ramchandren

Rod Ramchandren

University of Tennessee Medical Center, Knoxville, TN, United States

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Judah Friedman

Judah Friedman

Florida Cancer Specialists & Research Institute, Palm Springs, FL, United States

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John M. Burke

John M. Burke

US Oncology Research, The Woodlands, TX, United States

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Yuliya Linhares

Yuliya Linhares

Miami Cancer Institute, Baptist Health South, Florida, Miami, FL, United States

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Paul Gonzales

Paul Gonzales

Brooke Army Medical Center Fort Sam, Houston, TX, United States

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Mihir Raval

Mihir Raval

US Oncology Research, The Woodlands, TX, United States

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Rangaswamy Chintapatla

Rangaswamy Chintapatla

Kadlec Clinic, Kennewick, WA, United States

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Tatyana A. Feldman

Tatyana A. Feldman

John Theurer Cancer Center at Hackensack Meridian Health, Hackensack, NJ, United States

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Habte Yimer

Habte Yimer

US Oncology Research, The Woodlands, TX, United States

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Miguel Islas-Ohlmayer

Miguel Islas-Ohlmayer

US Oncology Research, The Woodlands, TX, United States

Oncology Hematology Care, Cincinnati, OH, United States

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Asad Dean

Asad Dean

US Oncology Research, The Woodlands, TX, United States

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Vishal Rana

Vishal Rana

University of Colorado Health Hematology and Oncology, Colorado Springs, CO, United States

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Mitul D. Gandhi

Mitul D. Gandhi

US Oncology Research, The Woodlands, TX, United States

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John Renshaw

John Renshaw

US Oncology Research, The Woodlands, TX, United States

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Linda Ho

Linda Ho

Seagen Inc., Bothell, WA, United States

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Michelle Fanale

Michelle Fanale

Seagen Inc., Bothell, WA, United States

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Wenchuan Guo

Wenchuan Guo

Seagen Inc., Bothell, WA, United States

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Hun Ju Lee

Hun Ju Lee

MD Anderson Cancer Center, Houston, TX, United States

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First published: 08 August 2023
Citations: 3

Abstract Topic: 17. Hodgkin lymphoma - Clinical

Background: Brentuximab vedotin (BV) is an antibody-drug conjugate approved for multiple cancer types, including previously untreated, adult, stage III or IV classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vinblastine, and dacarbazine (AVD). BV and nivolumab (N) are both individually active and well tolerated in patients with cHL and have distinct and complementary mechanisms of action. BV and nivolumab have been previously studied in combination and with multiagent chemotherapy as BV+AD (omitting vinblastine) and N+AVD. It was hypothesized that the combination of BV and nivolumab with doxorubicin and dacarbazine (AN+AD) would result in high response rates and a well-tolerated safety profile, with potentially less toxicity than vinblastine-containing regimens. SGN35-027 (NCT03646123; EudraCT Number 2020-004027-17; Part B) is an open-label, multiple part, multicenter, phase 2 clinical trial. Preliminary results of this study showed promising efficacy (objective response rate [ORR] 93%; complete response [CR] rate 88% at end of therapy [EOT]) with no cases of febrile neutropenia or Grade 5 adverse events (AEs) (Lee ASCO 2022).

Aims: Present updated safety and efficacy results of AN+AD as frontline treatment for patients with advanced stage cHL

Methods: Part B enrolled patients with stage II bulky mediastinal disease (≥10 cm), stage III, or stage IV cHL. Patients received up to 6 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]). The primary efficacy endpoint was CR rate at EOT. Key secondary endpoints included safety and tolerability, ORR, duration of response (DOR), duration of complete response (DOCR), and progression-free survival (PFS). Disease response and progression were assessed by investigator using Lugano Classification Revised Staging System for malignant lymphoma, incorporating Lymphoma Response to Immunomodulatory Therapy Criteria for nodal non-Hodgkin and Hodgkin lymphomas.

Results: Fifty-eight patients were enrolled; all but 1 patient received ≥1 dose of study drug. Among efficacy evaluable patients (n=56), ORR (CR+partial response [PR]) at EOT was 95% (95% CI: 85.1, 98.9); CR rate was 89% (95% CI: 78.1, 96.0). DOR of at least 15 months occurred in 92.7% (95% CI: 81.6, 97.9) of responders. Six (11%) patients had a PFS event: 5 disease progression, 1 death (sepsis, outside safety reporting period). The estimated PFS rate at 18 months was 92.6% (95% CI: 81.5, 97.2). Median follow-up was 18.8 months (95% CI: 17.9, 22.5).

Treatment-related AEs occurred in 56 (98%) patients; Grade ≥3 treatment-related AEs occurred in 19 (33%) patients. No febrile neutropenia or Grade 5 AEs occurred. Treatment-related serious AEs (SAEs) occurred in 8 (14%) patients. No patients died due to a treatment-related SAE. Treatment-emergent immune-mediated AEs (IMAEs) occurred in 20 (35%) patients; treatment-emergent IMAEs occurring in ≥5% of patients were hypothyroidism (5 [9%]), pneumonitis and rash maculo-papular (3 [5%] each). As of data cutoff (28 Nov 2022), all patients were off study drug; 51 (88%) remained in long-term follow-up.

Summary/Conclusion: The use of two active, targeted agents with distinct and complementary mechanisms of action for the frontline treatment of advanced stage cHL resulted in promising activity, safety, and tolerability. Updated safety results demonstrated continued tolerability of AN+AD with no new safety signals observed. AN+AD may provide a future frontline treatment option for patients with advanced stage cHL; long-term follow-up is ongoing.

Keywords: Clinical trial, Hodgkin’s lymphoma, Phase II

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