More than 65% of patients with anti-PD-L1-naive advanced melanoma responded positively to a combined therapy of the investigational agent HBI-8000, and nivolumab, researchers announced at the November 2024 Society for Immunotherapy of Cancer in Houston, Texas.
Additionally, researchers observed a median progression-free survival rate of 36.9 months (95% CI: 6.7, NE) suggesting that the combination of HBI-8000 and nivolumab offers promising results for patients in terms of tumor response and disease control, said Nikhil Khushalani, MD, vice chair of cutaneous oncology at Moffitt Cancer Center, Tampa, Florida.
“The treatment landscape for advanced melanoma is typically immunotherapy-based using an anti PD one backbone,” said Dr. Khushalani in his oral presentation on November 9. He reported that previous studies have shown that combining immune checkpoint inhibitors can lead to a higher response rate and longer progression-free survival, compared to using an anti-PD-1 monotherapy. However, he added, “this combination treatment is also linked to a greater risk of immune-related adverse events, some of which maybe chronic.”
HB1-8000 is an HDAC inhibitor that works by blocking the activity of histone deacetylase enzymes, involved in the regulation of gene expression. By inhibiting these enzymes, researchers suggest that HB1-8000 may improve antitumor immunity through epigenetic modulation within the tumor microenvironment.
Researchers conducted a phase 1b/2 clinical trial to explore whether adding HBI-8000 could improve the effectiveness of nivolumab, the standard treatment for advanced melanoma. The study assessed the combination therapy’s impact on melanoma growth, tumor size, patient survival, while also monitoring for adverse effects.
They enrolled 39 patients with advanced unresectable melanoma, who had not been previously treated with an anti PD 1 or PD L 1, or an immune checkpoint inhibitor, into the study between August 2016 until early 2021. The median age of the cohort was 63 years (ranging from 28 to 83), with 59% being male; Among them, 16 out of 39 (41%) had M1c disease and none had central nervous system metastases. About 87% (34 out of 39) had normal serum lactate dehydrogenase at baseline, a known prognostic factor in advanced melanoma.
All participants received HBI-8000 orally (37 at 30 mg BIW in Phases 1b and 2, and 2 at 40mg BIW in Phase 1b) in combination with intravenous nivolumab administered at the manufacturer’s approved dosing schedule. Disease status was monitored every 8 weeks using standard imaging and RECIST v1.1 criteria. Treatment was continued until disease progression, unacceptable toxicity, or completion of 24 months of therapy.
Researchers found that 65.8% of the patients evaluated (38 individuals) exhibited a response to the treatment. Among these patients, half (50%) experienced partial responses, indicating an improvement in their condition that fell short of complete resolution, while 15.8% of the patients achieved complete responses, with their condition either completely resolved or significantly improved. Overall, 87% of the patients benefitted clinically from the treatment, either through achieving a complete response, a partial response, or maintaining stable disease for at least 12 weeks.
The treatment was well-tolerated with fatigue, decreased appetite, nausea, diarrhea, abdominal pain, weight loss, and edema, being the most common treatment-related side effects associated with both drugs. Although, patients did develop neutropenia, lymphopenia, anemia, and thrombocytopenia, there was no evidence of clinically significant bleeding nor any episodes of febrile neutropenia recorded.
“Certainly, a 65% response rate is very encouraging but, I’m always a little cautious about seeing results, as promising as this,” said Dr. Khushalani. He emphasized that the true test will be in the phase 3 trial. That upcoming trial will assess the effectiveness of combining nivolumab with HBI-8,000 compared to using nivolumab alone as a first-line treatment for patients with unresectable or metastatic melanoma.
The story was supported by HUYABIO International, based in /San Diego, California.
– By Cara Gallo Massey
Cara Gallo Massey is an experienced journalist and content creator specializing in healthcare, holistic wellness, and medicine. She is a frequent contributor to HealthTech Hotspot. Her articles on subjects ranging from cancer prevention and treatment, longevity, medical imaging, nutrition, and more have appeared in a wide range of national magazines, local media, and professional consumer publications. During her career, she has also been the features editor for The National Enquirer, The Star, and The Globe, as well as a frequent contributor to women’s, luxury lifestyle, and professional medical publications.
