Nemvaleukin Alfa Plus Pembrolizumab Gets Fast Track Status for Platinum-Resistant Ovarian Cancer

Craig Hopkinson, MD

The FDA has granted a fast track designation to the interleukin-2 (IL-2) variant immunotherapy nemvaleukin alfa (nemvaleukin) in combination with pembrolizumab (Keytruda) for the treatment of patients with platinum-resistant ovarian cancer.¹

The investigational engineered fusion protein is composed of modified IL-2 and the high affinity IL-2 alpha receptor chain, which preferentially expands tumor-killing immune cells and avoids the activation of immunosuppression cells through selective binding to the intermediate-affinity IL-2 receptor complex. The selectivity of the agent is hypothesized to leverage the antitumor effects of existing IL-2 therapy and diminish select limitations.

Nemvaleukin plus pembrolizumab will be compared with investigator’s choice of chemotherapy in patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, as part of the global, open-label, phase 3 ARTISTRY-7 trial (NCT05092360), which was initiated on October 26, 2021.² Additional nemvaleukin and pembrolizumab monotherapy arms will also be evaluated.

“The fast track designation in platinum-resistant ovarian cancer highlights the potential clinical utility of nemvaleukin in combination with pembrolizumab in this difficult-to-treat disease for which there is no approved immunotherapy and there remains significant need for new treatment options,” Craig Hopkinson, MD, chief medical officer and executive vice president of Research & Development at Alkermes plc, stated in a press release. “We are excited to initiate…[the] ARTISTRY-7 phase 3 trial in platinum-resistant ovarian cancer, as we advance nemvaleukin toward potential registration and seek to help patients living with this disease.”

To be eligible for enrollment to ARTISTRY-7, patients need to be at least 18 years of age, have platinum-resistant or -refractory disease, have received at least 1 previous line of systemic therapy in the platinum-sensitive setting, have at least 1 measurable lesion per RECIST v1.1 criteria, and be willing to undergo a pretreatment tumor biopsy.³

If patients had primary platinum-refractory disease or primary platinum resistance, a histologically confirmed diagnosis of epithelial ovarian carcinoma with mucinous or carcinosarcoma subtype, or a nonepithelial tumor, they will be excluded. Other exclusion criteria include having previously received IL-2–based or IL-15–based cytokine therapy and prior exposure to any anti–PD-1/PD-L1 therapy.

Participants will be centrally allocated in a randomized 3:1:1:3 fashion to receive either nemvaleukin and pembrolizumab, pembrolizumab monotherapy, nemvaleukin monotherapy, or investigator’s choice of chemotherapy, which could include 1 of the following: pegylated liposomal doxorubicin (PLD), paclitaxel, topotecan, or gemcitabine.

Nemvaleukin will be given at a daily dose of 6 µg/kg on days 1 through 5 of 21-day treatment cycles. Pembrolizumab will be administered at a dose of 200 mg on day 1 of each 21-day cycle. PLD will be given at 40 mg/m² on day 1 of 28-day cycles; paclitaxel will be given at 80 mg/m² on days 1, 8, 15, and 22 of 28-day cycles; topotecan will be given at 4 mg/m² on days 1, 8, and 15 of 28-day cycles; and gemcitabine will be given at 1000 mg/m2 on days 1 and 8 if 21-day cycles.

The primary end point of the trial is investigator-assessed progression-free survival based on RECIST v1.1 criteria. Additional end points include objective response rate, overall survival, disease control rate, duration of response, time to response, cancer antigen-125 response, pharmacokinetics, pharmacodynamics, and safety.

Investigators plan to enroll approximately 376 patients to the trial.

“The initiation of our phase 3 study of nemvaleukin in platinum-resistant ovarian cancer is an important milestone for the nemvaleukin clinical development program and reflects our commitment to focusing on the high unmet need of patients living with difficult-to-treat cancers such as platinum-resistant ovarian cancer,” Hopkinson stated in a press release. “ARTISTRY-7 is designed to build upon the durable and deepening responses observed in heavily pretreated patients with platinum-resistant ovarian cancer in the ongoing ARTISTRY-1 trial [NCT02799095]. We look forward to sharing updates from ARTISTRY-7 as the study progresses and as we advance toward potential registration.”

Previously, in August 2021, the FDA granted a fast track designation to nemvaleukin for the treatment of patients with mucosal melanoma.⁴ In the phase 2 ARTISTRY-6 trial (NCT04830124), investigators are evaluating the antitumor activity, safety, and tolerability of nemvaleukin in this patient population. The study also includes a cohort of patient with advanced cutaneous melanoma who will receive subcutaneous nemvaleukin with the intent to establish single agent proof-of-concept with the latter dosing.⁵

References

1. Alkermes receives FDA fast track designation for nemvaleukin alfa in combination with pembrolizumab for the treatment of platinum-resistant ovarian cancer. News release. Alkermes plc. October 25, 2021. Accessed October 26, 2021. https://bit.ly/3ExZ6Th
2. Alkermes initiates ARTISTRY-7 phase 3 trial of nemvaleukin alfa in patients with platinum-resistant ovarian cancer. News release. Alkermes plc. October 26, 2021. Accessed October 26, 2021. https://prn.to/3pEvLC9
3. Phase 3 study of nemvaleukin alfa in combination with pembrolizumab (ARTISTRY-7). ClinicalTrials.gov. Updated October 25, 2021. Accessed October 26, 2021. https://www.clinicaltrials.gov/ct2/show/NCT05092360
4. Alkermes receives FDA fast track designation for nemvaleukin alfa for the treatment of mucosal melanoma. News release. Alkermes plc. August 2, 2021. Accessed October 26, 2021. https://bit.ly/2WMtb0G
5. Alkermes initiates ARTISTRY-6 trial of nemvaleukin alfa monotherapy in patients with melanoma. News release. Alkermes plc. April 27, 2021. Accessed October 26, 2021. https://bit.ly/3xf9Ql7