Nemvaleukin/Pembrolizumab Yield No OS Improvement in Ovarian Cancer

The phase 3 ARTISTRY-7 trial has been halted and nemvaleukin is no longer being developed for the treatment of patients with platinum-resistant ovarian cancer.

Nemvaleukin alfa, an engineered interleukin-2 (IL-2) variant immunotherapy, plus pembrolizumab (Keytruda) did not elicit a significant improvement in overall survival (OS) when compared with investigator’s choice of chemotherapy alone in patients with platinum-resistant ovarian cancer, according to a press release from the developer, Mural Oncology.¹

In the pre-specified interim analysis, which was conducted at 77% events (n = 219), the treatment combination achieved a median OS of 10.1 months compared with 9.8 months with investigator’s choice of chemotherapy (HR, 0.98). Additionally, the safety profile of nemvaleukin was consistent with previously reported data.

The phase 3 ARTISTRY-7 trial (NCT05092360) which found the aforementioned data has been halted and will not continue to the final analysis. The developer will cease the development of nemvaleukin in platinum-resistant ovarian cancer.

“We are disappointed for patients with ovarian cancer who are desperately lacking new treatment options. There has been a great deal of work across the industry in this immunologically cold tumor, yet there are still few treatment options that improve survival in this very difficult-to-treat tumor type,” Caroline Loew, PhD, chief executive officer at Mural Oncology, stated in the press release. “We are still on track to report topline data from our potentially registrational trial in mucosal melanoma later next quarter and will assess all available data to inform our next steps.”

ARTISTRY-7 was a randomized, open-label, multicenter trial that evaluated nemvaleukin with pembrolizumab vs investigator’s choice of chemotherapy in platinum-resistant ovarian cancer, fallopian tube cancer, or primary peritoneal cancer.

A total of 456 patients were randomly assigned to the 4 trial arms, in a 3:1:1:3 ratio, with only arms 1 and 4 intended to be used for statistical comparisons. In arm 1, patients received 6 µg/kg of nemvaleukin via intravenous infusion over 30 minutes on days 1 to 5 of each 21-day cycle and 200 mg of pembrolizumab via intravenous infusion over 30 minutes on day 1 of each cycle; in arm 2, patients received 200 mg of pembrolizumab via intravenous infusion on day 1 of each cycle; in arm 3, patients received 6 µg/kg of nemvaleukin via intravenous infusion on days 1 to 5 of each cycle; and in arm 4, patients received either 40 mg/m² of pegylated liposomal doxorubicin on day 1 of 28-day cycles at 1 mg/min for cycle 1 and over 60 minutes for subsequent cycles, 80 mg/m² of paclitaxel via 60 minutes intravenous infusion on days 1, 8, 15, and 22 of each cycle, 4 mg/m² of topotecan on days 1, 8, and 15 or 1.25 mg/m² on days 1 to 5 of each cycle, or 1000 mg/m² on days 1 and 8 of each cycle.²

Patients were 18 years or older and were required to have received at least 1 and no more than 5 prior lines of systemic therapy in the platinum-sensitive setting.

The trial’s primary end point was OS for up to 3 years. Secondary end points were objective response rate per investigator, disease control rate, duration of response, time to response, cancer antigen-125 response, progression-free survival, and incidence of treatment-emergent adverse events.

Nemvaleukin is also being evaluated in cohort 2 of the potentially registrational, phase 2 ARTISTRY-6 trial (NCT04830124) as a treatment in patients with mucosal melanoma; topline data is expected in Q2 of 2025. Additionally, readouts of less frequent intravenous nemvaleukin dosing in patients with cutaneous melanoma are expected from cohort 3, a monotherapy arm, in Q2 2025 and from cohort 4, a combination arm with pembrolizumab, in the second half of 2025.

Previously, in October 2021, the FDA granted fast track designation to nemvaleukin with pembrolizumab as a treatment for platinum-resistant ovarian cancer.³ In August 2021 and March 2021, the combination was granted fast track designation and orphan drug designation, respectively, in the treatment of mucosal melanoma.^4,5

References

1. Mural Oncology provides update on phase 3 ARTISTRY-7 trial of nemvaleukin in combination with KEYTRUDA® (pembrolizumab) in patients with platinum-resistant ovarian cancer. News release. Mural Oncology. March 25, 2025. Accessed March 26, 2025. https://tinyurl.com/yjecs6jy
2. Phase 3 study of nemvaleukin alfa in combination with pembrolizumab in patients with platinum-resistant epithelial ovarian cancer (ARTISTRY-7) (ARTISTRY-7). ClinicalTrials.gov. Updated June 28, 2024. Accessed March 26, 2025. https://tinyurl.com/ms79hjth
3. Alkermes receives FDA fast track designation for nemvaleukin alfa in combination with pembrolizumab for the treatment of platinum-resistant ovarian cancer. News release. Alkermes. October 25, 2021. Accessed March 26, 2025. https://tinyurl.com/3rjvyner
4. Alkermes receives FDA fast track designation for nemvaleukin alfa for the treatment of mucosal melanoma. News release. Alkermes. August 2, 2021. Accessed March 26, 2025. https://tinyurl.com/53tt7hsb
5. Alkermes announces FDA orphan drug designation for nemvaleukin alfa for treatment of mucosal melanoma. News release. Alkermes. March 11, 2021. Accessed March 26, 2025. https://tinyurl.com/y5ktw7ad