Nemvaleukin alfa (Alkermes) was mostly well tolerated and indicated antitumor activity as both monotherapy and in combination with pembrolizumab among patients with advanced solid tumors, according to study results presented at the annual meeting of the American Society of Clinical Oncology (ASCO), held virtually from June 4-8.
“Checkpoint inhibitors (CPIs) have demonstrated strong activity in several tumor types; however, patients develop resistance,” said lead investigator Valentina Boni, MD, PhD, an oncologist at the Clara Campal Comprehensive Cancer Center in Madrid, Spain. “Also, for some tumor types like ovarian cancer, the activity of anti-programmed death-1 (PD-1) and anti-PD-1 ligand 1 (PD-L1) monotherapy is limited.”
Boni said there is an unmet medical need to improve the therapeutic landscape and enhance several combinations of immunotherapies for advanced solid tumors, including using nemvaleukin, an interleukin-2 (IL-2) cytokine.
ARTISTRY-1 is an ongoing phase 1/2 global study, with sites in North America, Asia Pacific and the European Union.
Patients were divided into 3 groups. Part A was intravenous nemvaleukin monotherapy daily for 5 days followed by 9 days off, then daily for 5 days followed by 16 days off for subsequent cycles, with a dose escalation starting at 0.1 µg/kg that progressed to 14 µg/kg. Of the 43 patients, the median age was 61 years and 60% were male.
“The majority were refractory patients with progressive disease and with very limited treatment options,” Boni told Contemporary OB/GYN®. “Common tumor types included melanoma, renal cell carcinoma (RCC), prostate cancer, colon cancer, and uterine cancer.”
Part B also was intravenous nemvaleukin monotherapy using the same dosing schedule as Part A, with the recommended phase 2 dose of 6 µg/kg.
The group comprised 37 patients with melanoma and 25 patients with RCC, with a median age of 66 years. There were an equal number of men and women with melanoma versus about 90% male for RCC.
The 100 evaluable patients in Part C received nemvaleukin, either 3 µg/kg or 6 µg/kg, every 21 days in combination with pembrolizumab, which was administered on day 1 only at a dose of 200 mg.
The median age of patients in the group was 60 years, with an equal number of men and women. Among the tumor types were ovarian cancer, triple-negative breast cancer (TNBC), cervical cancer, and breast cancer.
The study, which presented safety and antitumor activity data as of March 19, 2021, found that adverse events were in general transient and easily manageable among all 3 groups of patients, who had been on nemvaleukin treatment for up to 72 weeks.
“We have also seen preliminary activity in a broad spectrum of tumor types, including tumor types not approved or typically responsive to checkpoint inhibitors (CPIs) and in patients pretreated with CPIs,” Boni said. “Furthermore, we have observed responses in platinum-resistant-ovarian cancer, a very difficult to treat cancer with limited treatment options.”
For patients who received combination therapy, 19 objective responses were observed. An additional 3 patients had stable disease for at least 6 months: 1 with hepatocellular carcinoma, 1 with ovarian cancer and 1 with NSCLC.
Combination immunotherapy with anti-PD-1 plus anti-CTLA-4 antibodies – for example, nivolumab plus ipilimumab -- improves outcomes of women with recurrent or persistent ovarian cancer, compared with anti PD-1 alone (nivolumab), according to Boni. “However, this combination has been associated with an increase in severe toxicities,” she said.
Still, the current study concludes that nemvaleukin in combination with pembrolizumab has a similar rate of serious adverse events as nemvaleukin monotherapy.
“Overall, the study data are very encouraging to me,” Boni said.
Boni reports no relevant financial disclosures.
Boni V. ARTISTRY-1, a Phase 1/2 study evaluating nemvaleukin administered intravenously as a monotherapy and in combination with pembrolizumab. Data presented at: American Society of Clinical Oncology Annual Meeting; June 4-8, 2021. Virtual. Accessed June 8, 2021.