CCTG HDC1 | SWOG S1826 Wednesday, June 14, 2023 A Phase III Randomized Study of Nivolumab (Opdivo) or Brentuximab Vedotin (Adcetris) plus AVD in Patients (age >/= 12 Years) with Newly Diagnosed Advanced Stage Classical Hodgkin Lymphoma The study results were presented at ASCO 2023 show that the immune checkpoint inhibitor nivolumab plus chemotherapy significantly reduced the risk of disease progression and disease-related death compared with standard treatment in pediatric and adult patients with previously untreated stage III or IV Hodgkin lymphoma. These results pave the way for nivolumab+AVD as new standard of care for advanced-stage Hodgkin lymphoma. The study compared immunotherapy drugs (nivolumab or brentuximab vedotin) when given with combination chemotherapy in treating patients with newly diagnosed stage III or IV classic Hodgkin lymphoma. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to cancer cells in a targeted way and delivers vedotin to kill them. Drugs used in chemotherapy, such as doxorubicin, vinblastine, and dacarbazine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. The addition of nivolumab or brentuximab vedotin to combination chemotherapy may shrink the cancer or extend the time without disease symptoms coming back. Dr Lois Shepherd, CCTG Senior Investigator"This study was a collaboration in trial development between the Children’s Oncology Group (COG) and National Clinical Trials Network (NCTN) cooperative groups in the US and Pediatric centres in Canada through the CCTG," says CCTG Senior Investigator Dr Lois Shepherd. "The accrual was completed well ahead of schedule and Canada recruited 30 patients over the last year of the study. The results have been described as practice changing for newly diagnosed advanced Hodgkin lymphoma." Junior faculty from each cooperative group were key players in trial development and CCTG played an active role under the leadership of Dr. Kelly Davison from McGill University Health Centre. Other Canadians actively involved included Drs. Angela Punnett from Sick Kids and David Hodgson from Princess Margaret Cancer Centre. Results: 994 pts were enrolled from 7/9/19 to 10/5/22; 976 were eligible and randomized to N-AVD (n=489) or BV-AVD (n=487). Median age was 27y (range, 12-83y), 56% of pts were male, 76% were white, 12% were black, and 13% were Hispanic. 24% of pts were < 18y, 10% were > 60y, and 32% had IPS 4-7. So far, < 1% of pts received RT. At the planned 2nd interim analysis (50% of total PFS events) the SWOG Data and Safety Monitoring Committee recommended to report the primary results because the primary PFS endpoint crossed the protocol-specified conservative statistical boundary. 30 PFS events occurred after N-AVD vs 58 events after BV-AVD. With a median follow-up of 12.1 months, PFS was superior in the N-AVD arm [HR 0.48, 99% CI 0.27-0.87, one-sided p=0.0005); 1y PFS: N-AVD, 94%, BV-AVD, 86%. 11 deaths (7 due to adverse events, AE) were observed after BV-AVD compared to 4 after N-AVD (3 due to AE). The rate of grade (gr) ≥ 3 hematologic AE was 48.4% (45.1% gr ≥ 3 neutropenia) after N-AVD compared to 30.5% (23.9% gr ≥ 3 neutropenia) after BV-AVD. Rates (any gr) of febrile neutropenia (5.6% N vs 6.4% BV), pneumonitis (2.0% N vs 3.2% BV), ALT elevation (30.7% N vs 39.8% BV), and colitis (1% N vs 1.3% BV) were similar. Hypo/hyperthyroidism was more frequent after N-AVD (7%/3% N vs <1% BV) while peripheral neuropathy (any gr) was more common after BV-AVD (sensory: 28.1% N vs 54.2% BV; motor: 4% N vs 6.8% BV). Conclusions: N-AVD improved PFS vs BV-AVD in pts with AS HL. Few immune AEs were observed and < 1% of pts received RT. Longer follow-up is needed to assess OS and PROs. S1826, the largest HL study in NCTN history, is a key step towards harmonizing the pediatric and adult treatment of AS HL. Funding provided by: National Cancer Institute of the National Institutes of Health U10CA180888 and U10CA180819 and Bristol-Myers Squibb. For more information please visit the HDC1 members trial page.