HBI-8000 Plus Nivolumab Is Safe, Active in Melanoma
The combination of HBI-8000 and nivolumab induced a response in nearly two-thirds of patients with advanced melanoma and no prior anti–PD-1/PD-L1 treatment.
Tumor concept illustration of melanoma: © picture-waterfall - stock.adobe.com
Combining the novel agent HBI-8000 with nivolumab (Opdivo) showed promising efficacy and tolerability in patients with melanoma and no prior anti–PD-1/PD-L1 treatment, according to findings from a phase 2 trial presented at the Society for Immunotherapy of Cancer (SITC) 2024 Annual Meeting.1,2
A total of 39 eligible patients were enrolled in the study and treated with HBI-8000 at 30 mg twice weekly (BIW) plus nivolumab in phases 1b and 2 (n = 37), or HBI-8000 at 40 mg BIW plus nivolumab in phase 1b (n = 2). The overall response rate for the 38 patients evaluable for efficacy was 65.8%. This included 6 (15.8%) complete responses and 19 (50%) partial responses. The clinical benefit rate was 87%. Further, with a median follow-up of 37 months, the median progression-free survival was 36.9 months (95% CI, 6.7 to not evaluable), and the median duration of response was not reached at the time of this analysis.
For safety, the most common treatment-related grade 3 or higher adverse events (AEs) included colitis (n = 4); fatigue, decreased appetite, pancreatitis, and diarrhea (n = 3 each); and abdominal pain and weight loss (n = 2 each). The most common treatment-related laboratory grade 3 or higher AEs were hypophosphatemia (n = 9), neutropenia (n = 8), lymphopenia (n = 6), anemia (n = 3), increased alanine aminotransferase and thrombocytopenia (n = 2 each). No febrile neutropenia was reported and 17 patients discontinued treatment due to AEs.
"We are pleased to share the final phase 2 results of the HBI-8000 and nivolumab combination in patients with advanced melanoma at this year's SITC conference," said Nikhil Khushalani, MD, senior member and vice chair, Department of Cutaneous Oncology from Moffitt Cancer Center, in a press release. "The combination appears safe and effective in this phase 2 study, which may show great promise in this patient population. HBI-8000 plus nivolumab could be an important addition to the armamentarium of oncologists treating this disease and is currently being investigated in a phase 3 study."
Based on these findings, a global phase 3 trial (NCT04674683) of HBI-8000 plus nivolumab vs nivolumab alone for the treatment of patients with unresectable or metastatic melanoma is currently ongoing.
Background of HBI-8000 and the Phase 2 Study
HBI-8000 is an oral selective histone deacetylase inhibitor that has led to multiple effects on immune cell function in the tumor microenvironment. When given with nivolumab, the agent has led to encouraging efficacy signals for patients with advanced and metastatic melanoma.1
Further, prior data on HBI-8000 has shown there to be clinically meaningful advantages when compared with traditional double immune checkpoint inhibitor combinations.1 This offers patients an oral treatment in combination with nivolumab that is less toxic with improved efficacy.
In the phase 1b/2 trial, investigators assessed the combination of HBI 8000 with nivolumab for the treatment of patients with advanced melanoma, kidney cancer, and non–small cell lung cancer.
Enrollment was open to patients with metastatic melanoma not previously treated with PD(L)-1 inhibitors who had measurable disease, an ECOG performance status of 0 or 1, and adequate hematologic and biochemical parameters. Those with previously treated stable brain metastases who did not require steroids were also eligible for enrollment.
The median age of those enrolled was 63 years (range, 28-83) and 59% of patients were male. Normal LDH was seen in 87% of patients, 41% had M1c disease, and no patients had central nervous system metastases.
According to findings presented at SITC, the investigators determined the recommended phase 2 dose of HBI-8000 to be 30 mg orally BIW plus nivolumab given via intravenous infusion at the manufacturer's approved dosing schedule. Patients received treatment until disease progression, unacceptable toxicity, or completion of 24 months of therapy, and disease status was assessed by standard imaging using RECIST v1.1 every 8 weeks.
"The promising results from the HBI-8000 and nivolumab combination represent a significant advancement in treating advanced melanoma," said Mireille Gillings, PhD, president, chief executive officer & executive chair at HUYABIO, in a press release. "Coupling oral convenience with a reduction in immune-related toxicities will give clinicians new tools to improve patient outcomes. We are proud to contribute to this new era of immunotherapy that prioritizes both efficacy and patient well-being."
REFERENCES:
HUYABIO presents positive phase 2 data on HBI-8000 and nivolumab combination for advanced melanoma. News release. HUYABIO International. November 8, 2024. Accessed November 20, 2024. https://tinyurl.com/y38657hk
Khushalani NI, Brohl A, Markowitz J, et al. HBI-8000, a class I histone deacetylase (HDAC) inhibitor, in combination with nivolumab for treatment of anti-PD(L)1-naive advanced melanoma: final analysis of Study HBI-8000-302. Presented at: 2024 SITC Annual Meeting; November 6-10, 2024; Houston, TX. Abstract 620.
