Novel immunotherapy approach benefits patients with melanoma, leptomeningeal disease
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Key takeaways:
- Treatment appeared well tolerated at the highest dose level of 50 mg.
- Researchers observed only mild grade 1 or grade 2 adverse events.
Concurrent intrathecal and IV nivolumab appeared safe and showed potential efficacy among a small cohort of patients with melanoma and leptomeningeal disease, according to results of a phase 1/1b study published in Nature Medicine.
Researchers observed early evidence of clinical benefit even among some patients who had previously received systemic anti-PD-1 therapy, researchers noted.
Rationale and methodology
Patients with leptomeningeal disease have very poor survival outcomes even with recent access to new therapies; thus, treatment for this complication of cancer remains an area of huge unmet need, Isabella C. Glitza Oliva, MD, PhD, associate professor in the department of melanoma medical oncology at The University of Texas MD Anderson Cancer Center, told Healio.
“In addition to facing poor survival and high morbidity, there are very few clinical trials for patients with leptomeningeal disease and standard of care options don’t often lead to the most meaningful benefits,” she said. “Our goal is to help these patients as much as possible.”
The interim analysis of the ongoing single-arm, first-in-human study included 25 patients (median age, 43 years) with melanoma and leptomeningeal disease. Nearly all patients (93%) received prior systemic therapy, including immune checkpoint inhibitors (84%), BRAF/MEK inhibitors (64%) and chemotherapy (12%). All patients who previously received checkpoint inhibitors had anti-PD-1 therapy.
Researchers assigned patients to intrathecal nivolumab (Opdivo, Bristol Myers Squibb) alone in cycle one and added IV nivolumab in subsequent cycles.
In the dose-expansion cohort, researchers evaluated 5 mg, 10 mg, 20 mg and 50 mg of intrathecal nivolumab concurrent with a flat dose of IV nivolumab.
Safety and the recommended intrathecal dose of nivolumab served as the primary outcomes, with OS as a secondary outcome.
Findings
Results showed the novel treatment approach appeared well-tolerated at the highest dose level of 50 mg.
Researchers observed only mild grade 1 or grade 2 adverse events and no dose-limiting toxicities. Common treatment-associated adverse events included nausea, dizziness and vomiting.
Efficacy results showed median OS of 4.9 months and OS rates of 44% at 26 weeks and 26% at 52 weeks.
Implications
Prospective clinical trials such as this one using intrathecal immunotherapy for patients with leptomeningeal disease are not only feasible, but should be encouraged, Glitza Olivia told Healio.
“This study shows the enormous potential of using intrathecal immunotherapy for this poorly understood disease, and we hope that future clinical trials will lead us to further insights so we can find more effective ways to help our patients,” she said. “There are significant translational efforts being made, including plans for another upcoming clinical trial using intrathecal immunotherapy.”
References:
- Glitza Olivia IC, et al. Nat Med. 2023;doi:10.1038/s41591-022-02170-x.
- Novel immunotherapy delivery approach safe and beneficial for some melanoma patients with leptomeningeal disease (press release). Available at: www.mdanderson.org/newsroom/novel-immunotherapy-delivery-approach-safe-beneficial-some-melanoma-patients-leptomeningeal-disease.h00-159617067.html. Published March 30, 2023. Accessed April 6, 2023.
For more information:
Isabella C. Glitza Oliva, MD, PhD, can be reached at icglitza@mdanderson.org.
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