SWOG Cancer Research Network Phase 3 trial, led by City of Hope

Los Angeles and Portland, Ore. — Phase 3 trials have shown that patients with advanced (3 or 4) stage of classic Hodgkin lymphoma who are initially treated with nivolumab, a PD-1 checkpoint inhibitor, and AVD (N-AVD) chemotherapy have a significantly lower risk of developing cancer worse than patients treated with brentuximab vedotin, monoclonal antibodies, and AVD (BV-AVD) a year after starting treatment.

Ninety-four percent of adolescent and adult patients in the N-AVD group had progression-free survival compared to 86% in the BV-AVD group. N-AVD was also well tolerated as there were few serious immune-related adverse events in the S1826 trial. The median follow-up was 12.1 months.

The latest findings will be presented by Alex Herrera, MD of the City of Hope, at the 2023 ASCO Plenary Session, June 4, at 2:53 PM CT in Hall B1 and will be featured in ASCO’s official press programme.

The lead investigator on the study, Herrera is chief of the Division of Lymphoma at the City of Hope, one of the largest cancer research and treatment organizations in the United States, and is an investigator on the SWOG Cancer Research Network, a clinical trial group funded by the National Cancer Institute ( NCI), part of the National Institutes of Health.

“The results have been amazing. The combination of nivolumab and chemotherapy is efficacious and safe in patients with classic Hodgkin’s lymphoma Stage 3 or 4 as initial treatment,” said Herrera, “This therapy is ready to become the standard for the treatment of advanced Hodgkin’s lymphoma. This is indeed great news for patients with this cancer because there are other treatment options that are effective and safe for them.”

Georgie Garabet, 43, of Glendora, California, is one of the patients participating in the trial. When Garabet started feeling ill in early 2020, he was a 40 year old father of two children under the age of 3. Symptoms include uncontrollable itching all over his body and severe weight loss. After several trips to the emergency room and to her primary care doctor, she was finally diagnosed with Stage 3 Hodgkin’s lymphoma.

“I panic when I hear the word cancer,” said Garabet. At the same time, he was relieved to know what was causing his symptoms.

Garabet met Herrera and immediately felt in good hands. “He explained everything very well,” he added. Garabet is enrolled in the trial. After her first infusion she felt tired but it was the worst she had felt during the treatment. After only four infusions, he recovered. He was advised to continue treatment if any cancer remained, which he did. “Now when people tell me they have cancer, I tell them not to panic. Now there are many medicines,” he added.

The S1826 trial, supported by NCI and led by SWOG, is the largest classic Hodgkin lymphoma study ever conducted in the NCI National Clinical Trials Network and also represents a diverse patient population. About a quarter of enrolled patients were black or Hispanic. A partnership with the Children’s Oncology Group (COG) helped ensure the trial included young adolescents, and that a quarter of enrolled patients were under 18 years of age. Nearly two-thirds of all patients have stage 4 cancer.

“This study speaks to the power of the National Clinical Trials Network and is an excellent example of the transformative work that NCI funded,” said Jonathan Friedberg, MS, MMSc., senior author of the study, chair of the SWOG Cancer Research Network’s lymphoma committee and director of the Wilmot Cancer Institute. at the University of Rochester. “Hodgkin’s lymphoma is not a common disease and NCTN allows a large network of more than 200 pediatric and adult community providers and academic medical centers to work together. Because of this, we can get data very quickly and have a direct impact on patient care. This is an important investment in cancer research and treatment.”

Patients with previously untreated Stage 3 or 4 classic Hodgkin’s lymphoma and aged 12 years or older were eligible for the trial. Out of a total of 976 eligible patients, 489 were enrolled in the N-AVD group (nivolumab plus Adriamycin, vinblastine and dacarbazine), while 487 were part of the BV-AVD group. Each group received six infusion cycles of each combination therapy.

As expected with combination chemotherapy, the most common side effects included gastrointestinal and haematological toxicity, and fatigue. However, less than 1% of patients required radiation after the treatment trial, which represents a dramatic reduction in the proportion of patients initially treated for Hodgkin’s lymphoma who required radiation, especially among pediatric patients.

“The ability to maintain high relapse-free survival rates with minimal use of radiation therapy in children with newly diagnosed advanced Hodgkin’s lymphoma will be a paradigm shift,” said Sharon Castellino, MD, M.Sc., chair of the COG Hodgkin lymphoma committee. and director of the Leukemia and Lymphoma Program at Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta, Winship Cancer Institute at Emory University.

Brentuximab vedotin is the first drug-antibody conjugate developed for classic Hodgkin’s lymphoma. Several studies have shown that incorporating therapy into frontline treatment improves progression-free survival and overall survival. Despite the improved results, there are still serious side effects; recurrence may occur.

“There is clearly a need to increase frontline therapy for Hodgkin’s lymphoma, especially since the disproportionate number of patients with this disease are adolescents and young adults,” added Herrera.

PD-1 checkpoint inhibitors are a powerful and growing form of immunotherapy used to treat melanoma, kidney cancer, head and neck cancer, recurrent or difficult-to-treat Hodgkin’s lymphoma and other cancers. The PD-L1 protein is expressed on Hodgkin’s lymphoma tumor cells and helps cancer by signaling immune cells, such as T cells, to stop working against the tumor.

Checkpoint inhibitors block the PD-L1 protein from helping the immune system and, in particular, T cells, do what they are designed to do, eradicate cancer. In this study, adding nivolumab to chemotherapy worked so well that some patients went into remission after just a few treatments.

Next steps for the trial include following patients to measure progression-free survival, overall survival, and other patient outcomes.

Funding was provided by: National Cancer Institute of the National Institutes of Health U10CA180888, U10CA180819, U10CA180820, U10CA180821, U10CA180863, U10CA180886 and Bristol-Myers Squibb through a Cooperative Research and Development Agreement between NCI and BMS. Brentuximab vedotin is provided by Seagen.

In addition to Herrera and Friedberg, co-authors on the presentation included Michael L. LeBlanc, Ph.D., SWOG Center for Statistics and Fred Hutchinson Cancer Center; Sharon M. Castellino, MD, M.Sc., Emory University, Aflac Center for Cancer and Blood Disorders, Atlanta Children’s Health Services; Hongli Li, MS, SWOG Center for Statistics and Fred Hutchinson Cancer Center; Sarah C. Rutherford, MD, Weill Cornell Medicine-New York Presbyterian Hospital; Andrew M Evens, DO, M.Sc., Rutgers Cancer Institute in New Jersey; Kelly Davison, MD, McGill University; Angela Punnett, MD, Sick Children’s Hospital, Toronto; David C. Hodgson, MD, MPH, Department of Radiation Oncology, Princess Margaret Cancer Center, University Health Network; Susan K Parsons, MD, MRP, Tufts Medical Center, Tufts University School of Medicine; Sairah Ahmed, MD, University of Texas MD Anderson Cancer Center; Carla Casulo, MD, Division of Hematology/Oncology, University of Rochester; Nancy L. Bartlett, MD, University of Washington School of Medicine in St. Louis; Joo Y. Song, MD, Department of Pathology, City of Hope; Richard F. Little, MD, Cancer Therapy Evaluation Program, National Cancer Institute; Brad S. Kahl, MD, University of Washington School of Medicine at St. Louis; John P. Leonard, MD, Weill Cornell Medicine-New York Presbyterian Hospital; Sonali M. Smith, MD, Department of Oncology, University of Chicago; and Kara M. Kelly, MD, Department of Pediatric Oncology, Roswell Park Comprehensive Cancer Center.

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About SWOG

SWOG Cancer Research Network is part of the National Cancer Institute’s National Clinical Trials Network and the NCI Community Oncology Research Program and is part of the nation’s oldest and largest publicly funded cancer research network. SWOG has more than 18,000 members in 45 states and nine foreign countries who design and conduct clinical trials to improve the lives of people with cancer. SWOG trials have resulted in the approval of 14 cancer drugs, changed more than 100 standards of cancer care, and saved more than 3 million years of human life. Learn more at swog.org, and follow us on Twitter at @SWOG.

About the City of Hope

The City of Hope’s mission is to provide the medicine of tomorrow to the people who need it today. Founded in 1913, City of Hope has grown to become one of the largest cancer research and care organizations in the US and one of the leading research centers for diabetes and other life-threatening diseases. City of Hope research has been the basis for many breakthrough cancer drugs, as well as synthetic human insulin and monoclonal antibodies. With an independent comprehensive cancer center designated by the National Cancer Institute at its core, City of Hope provides a unique integrated model for patients spanning cancer care, research and development, academics and training, and innovation initiatives. City of Hope’s growing national system includes its campus in Los Angeles, a network of clinical care locations in Southern California, a new cancer center in Orange County, California, and treatment facilities in Atlanta, Chicago, and Phoenix. City of Hope’s group of affiliated organizations includes the Translational Genomics Research Institute and AccessHope^TM. For more information about the City of Hope, follow us on Facebook, TwitterYouTube, Instagram, and LinkedIn.