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Well-known for its neurological drug development programs,Alkermeshas firmly planted its flag as an oncology company at the American Society of Clinical Oncology (ASCO)’s annual meeting. The Ireland-based company presented data from its ARTISTRY-1 clinical trial for nemvaleukin alfa immunotherapy that has laid a foundation for the future.
Speaking to BioSpace ahead of the conference, Jessicca Rege, vice president and head of oncology at Alkermes, said the data from the study confirmed the design hypothesis of the Phase I/IIARTISTRY-1 studyby demonstrating preferential expansion of CD8+ T cells and NK cells with minimal effect on Tregs. Nemvaleukin alfa is the company’s novel, investigational, engineered interleukin-2 (IL-2) variant immunotherapy that is comprised of modified IL-2 and the high-affinity IL-2 alpha receptor chain. Nemvaleukin is designed to selectively expand tumor-killing immune cells while avoiding the activation of immunosuppressive cells through preferential binding to the intermediate-affinity IL-2 receptor complex. Alkermes is investigating nemvaleukin as both a monotherapy and in combination with Merck’s vaunted checkpoint inhibitor, Keytruda.
At ASCO, Rege will, for the first time, share the entirety of the ARTISTRY-1 program. She said the data seen in the study has checked all of the boxes Alkermes was hoping to see. Rege called ARTISTRY-1 a foundational study that supports the continued development of nemvaleukin, particularly as a monotherapy.
Data from ARTISTRY-1 showed that nemvaleukin demonstrated anti-tumor activity with durable responses as a stand-alone treatment for patients with mucosal melanoma and renal cell carcinoma (RCC) whose disease has progressed following treatment with a checkpoint inhibitor. Rege noted that while checkpoint inhibitors have revolutionized immuno-oncology, there are still a large number of patients who do not respond to those therapeutics. Through selective targeting of the IL-2 pathway, nemvaleukin may be able to deliver significant clinical benefit across multiple tumor types, all while mitigating toxicities that are associated with high-dose recombinant-IL-2, she said.
As a monotherapy, data from ARTISTRY-1 showed that in patients with advanced melanoma or renal cell carcinoma, treatment with nemvaleukin generated a partial response in 10 patients and stable disease in 41 patients. All melanoma patients who achieved a partial response with nemvaleukin monotherapy had previously progressed on treatment with a checkpoint inhibitor. Of the six evaluable mucosal melanoma patients, two patients achieved a partial response, including one confirmed response. One of those patients has been receiving nemvaleukin monotherapy for more than two years, achieving a duration of response of 79 weeks.
In RCC, of 22 evaluable patients, four achieved a partial response, three of which were confirmed. All renal cell carcinoma patients who achieved a partial response with nemvaleukin monotherapy had previously progressed on treatment with a checkpoint inhibitor.
Rege said that data from ARTISTRY-1 provided the company with important information regarding nemvaleukin’s pharmacokinetic and pharmacodynamic profile. Nemvaleukinearned Fast Track designationas well asOrphan Drug designationfrom the U.S. Food and Drug Administration for mucosal melanoma.
Nemvaleukin is also being assessed in combination with Keytruda (pembrolizumab) through acollaboration forgedwithMercklast year in the ARTISTRY-7 study.
Data from the ongoing ARTISTRY-1 program showed that out of the 137 patients who were evaluable by the ASCO cutoff date, four showed a complete response and 18 saw a partial response. Stable disease was seen in 60 patients and the overall median duration of response was 23 weeks. Both of the complete responses and two of the partial responses were in patients with platinum-resistant ovarian cancer (PROC). Median duration of response for PROC was 53 weeks. The primary endpoint of ARTISTRY-7 is progression-free survival.
Last year, FDAawardedFast Track designation to the combination of nemvaleukin and Keytruda for the treatment of PROC.
Rege noted that there is a “synergistic effect” between checkpoint inhibitors and nemvaleukin.
Expressing excitement for the results seen in ARTISTRY-1 and what the future holds for Alkermes’ oncology pipeline, Rege called the data Alkermes’ foundational element. The company is pushing forward with other ARTISTRY clinical programs, including the ARTISTRY-7 Phase III study in PROC, as well as ARTISTRY-3, a study assessing intravenous dosing of nemvaleukin as a monotherapy in multiple solid tumors and ARTISTRY-2, which is assessing subcutaneous dosing of nemvaleukin.
“Alkermes is not known for oncology. We’re coming into the space with a nice foundational building block and building a great portfolio,” she said.
Rege joined Alkermes two years ago when the company was kick-starting its oncology pipeline. When she joined as head of oncology, Rege said she came in with a mindset that although the science can be exciting, they ultimately serve the patient who receives the medication. For many of them, the need for treatment is a matter of life and death. Pointing at the ARTISTRY-1 data, Rege reiterated that this is the foundation that will lead Alkermes’ oncology program into the future.
“When we’re talking about cancer, we have a sense of urgency. At Alkermes, we’ve done well with this sense. In order to get the maximum potential, we have to be focused,” she said. “It’s great when we can offer another birthday, another graduation or the chance to meet a grandchild to these patients. I try to remind my team that we are the voice of the patients. Cancer has impacted so many people, even us. Everything we can do to move these drugs forward is critical.”