Nemvaleukin Lacks OS Benefit Over Chemo in Platinum-Resistant Ovarian Cancer

The phase 3 ARTISTRY-7 trial (NCT05092360) will be discontinued after data from a prespecified interim analysis showed no statistically significant improvement to overall survival (OS) with nemvaleukin alfa (ALKS 4230; nemvaleukin) plus pembrolizumab (Keytruda) when compared with investigator’s choice of chemotherapy in patients with platinum-resistant ovarian cancer.¹

A readout of topline data from ARTISTRY-7 is expected in the second quarter of 2025.

The drug’s developer, Mural Oncology, shared that they believe the study is highly unlikely to achieve success at the final OS analysis and announced that they will subsequently cease the development of nemvaleukin for this patient population.

According to topline findings from the prespecified first interim analysis of ARTISTRY-7, the median OS with the nemvaleukin combination was 10.1 months per independent data monitoring committee review vs 9.8 months with investigator’s choice of chemotherapy (HR, 0.98).

“We are disappointed for [patients with] ovarian cancer desperately lacking new treatment options,” Caroline Loew, PhD, chief executive officer of Mural Oncology, stated in a news release. “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. 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 [for nemvaleukin].”

Moreover, findings from the first interim analysis of ARTISTRY-7 showed the agent’s safety profile was generally consistent with previously reported data. In the broader clinical program, nemvaleukin’s safety profile is well-characterized and favorable as both monotherapy and in combination with pembrolizumab.

Nemvaleukin is an engineered fusion protein designed to harness the antitumor properties of interleukin 2 (IL-2) in tandem with reducing its dose-limiting toxicities. The agent selectively binds to the intermediate-affinity IL-2 receptor and is simultaneously sterically blocked from engaging the high-affinity IL-2 receptor. This molecular design promotes the preferential expansion of antitumor CD8-positive T cells and natural killer cells and minimizes the expansion of immunosuppressive regulatory T cells.

ARTISTRY-7 enrolled patients at least 18 years of age with histologically confirmed platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who received at least 1 prior line of systemic therapy in the platinum-sensitive setting and up to 5 prior lines of systemic therapy in the platinum-resistant setting.² Notably, at least 1 prior line of therapy needed to contain bevacizumab (Avastin). Other key inclusion criteria consisted of at least 1 measurable lesion per RECIST 1.1 criteria.

Patients were randomly assigned in a 3:1:1:3 fashion to receive nemvaleukin at 6 µg/kg per day on days 1 through 5 of each 21-day cycles plus pembrolizumab at 200 mg once every 3 weeks; pembrolizumab alone; nemvaleukin alone; or investigator’s choice of chemotherapy.

OS was the study’s primary end point. Secondary end points included objective response rate (ORR), disease control rate, duration of response (DOR), time to response (TTR), CA-125 response, and safety.

Ongoing investigations of nemvaleukin include the potentially registrational phase 2 ARTISTRY-6 trial (NCT04830124), which is evaluating the agent’s antitumor activity, safety, tolerability, pharmacokinetics, and pharmacodynamics as both monotherapy or in combination with pembrolizumab in patients with inoperable or metastatic cutaneous or mucosal melanoma.^1,3

The multicenter, open-label study is enrolling patients who were previously treated with an anti–PD-(L)1 therapy with or without a CTLA-4 inhibitor; who have an ECOG performance status of 0 or 1; and who have adequate hematologic reserve and hepatic and renal function.³ Cohorts 1 and 3 will comprise patients with advanced cutaneous melanoma; cohorts 2 and 4 will include those with mucosal melanoma.

Those in cohort 1 are receiving a subcutaneous injection of nemvaleukin every 7 days; in cohort 2, a daily dose of nemvaleukin is being intravenously (IV) administered over 30 minutes for 5 consecutive days; in cohort 3, a less frequent dosing schedule is being used, consisting of IV infusion of nemvaleukin over 30 minutes on days 1 and 8 of a 21-day cycle; in cohort 4, patients are receiving the less frequent dosing schedule of nemvaleukin alongside 200 mg of IV pembrolizumab on day 1 of a 21-day cycle.

The study’s primary end point is centrally-assessed ORR in cohorts 1 and 2, and investigator-assessed ORR in cohorts 3 and 4. Key secondary end points include DCR, progression-free survival, DOR, TTR, and safety.

A topline data readout from this trial is anticipated in the second quarter of 2025.¹ Pending patient enrollment, preliminary data for less-frequent intravenous dosing of nemvaleukin patients with cutaneous melanoma are expected in the second quarter of 2025 for cohort 3 and in the second half of 2025 for cohort 4.

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 25, 2025. https://ir.muraloncology.com/news-releases/news-release-details/mural-oncology-provides-update-phase-3-artistry-7-trial
2. Phase 3 study of nemvaleukin alfa in combination with pembrolizumab in patients with platinum-resistant epithelial ovarian cancer (ARTISTRY-7). ClinicalTrials.gov. Updated June 28, 2024. Accessed March 25, 2025. https://clinicaltrials.gov/study/NCT05092360
3. Nemvaleukin alfa monotherapy and in combination with pembrolizumab in patients with advanced cutaneous or mucosal melanoma - ARTISTRY-6 (ARTISTRY-6). Clinicaltrials.gov. Updated July 1, 2024. Accessed March 25, 2025. https://clinicaltrials.gov/study/NCT04830124