Trials of Nanrilkefusp Alfa Discontinued in Advanced Solid Tumors

Illustration of a tumor: ©Juan Gärtner - stock.adobe.com

Ongoing clinical trials of nanrilkefusp alfa (SOT101) as a monotherapy and in combination with pembrolizumab (Keytruda) and cetuximab (Erbitux) for the treatment of patients with advanced solid tumors will be discontinued.

According to Sotio Biotech, nanrilkefusp alfa’s manufacturer, interim data from trials evaluating the agent have not shown enough efficacy to warrant development in larger randomized trials.¹

"While we are disappointed with this outcome, we will continue to gather and analyze the full body of data from these studies to inform our future development plans for nanrilkefusp alfa, especially its potential utility in combination with other cancer immunotherapies," said Richard Sachse, MD, PhD, chief medical officer of Sotio Biotech, in a press release.

Nanrilkefusp alfa was being evaluated in 3 clinical trials. AURELIO-03 (NCT04234113), a phase 1 trial, and AURELIO-04 (NCT05256381), a phase 2 trial, were evaluating nanrilkefusp alfa in combination with pembrolizumab for advanced solid tumors. AURELIO-05 (NCT05619172), a phase 2 trial, was evaluating nanrilkefusp alfa in combination with cetuximab for colorectal cancer.¹

Nanrilkefusp alfa is a fusion protein of IL-15 and the IL-15 receptor α sushi+ domain. Murine models showed a synergistic effect between nanrilkefusp alfa and anti-PD-1 antibodies. Interim data from the AURELIO-03 trial were published in June 2022 and showed that nanrilkefusp alfa in combination with pembrolizumab resulted in a favorable safety profile. One complete remission and several partial responses were observed.²

SOTIO Biotech will continue to work on its immunocytokine platform, including preclinical development of SOT201, an IL-15 superagonist. SOT201 is on track to enter phase 1 development in the second quarter of 2024.

"With SOT201 we are advancing an even more differentiated program toward the clinic, combining checkpoint inhibition with IL-15 activation to produce a dual-acting therapy of great potential," said Radek Spisek, MD, PhD, chief executive officer of Sotio, in a press release.¹

Several other companies are developing IL-15 candidates, including Nektar Therapeutics. The manufacturer is conducting a phase 2/3 trial (NCT05664217) for its IL-15 receptor agonist, NKTR-255, following CD19-directed chimeric antigen receptor T-cell therapy in patients with relapsed/refractory large B-cell lymphoma.This study has an estimated enrollment of 400 patients and an estimated completion date of January 2029.³

REFERENCES:

1. SOTIO provides updates on interim data from cliincial trials of narilkefusp alfa. News release. Sotio Biotech. October 13, 2023. Accessed October 16, 2023. https://tinyurl.com/ycxu573

2. Garralda E, Naing A, Galvao V, et al. Interim safety and efficacy results from AURELIO-03: a phase 1 dose escalation study of the IL-2/IL-15 receptor ßy superagonist SOT101 as a single agent and in combination with pembrolizumab in patients with advanced solid tumors. J Clin Oncol. 2022;40(suppl 16):2502. doi:10.1200/JCO.2022.40.116_suppl.2502

3. NKTR-255 vs placebo following CD19-directed CAR-T therapy in patients with relapsed/refractory large B-cell lymphoma. ClinicalTrials.gov. Updated September 1, 2023. Accessed October 16, 2023. https://tinyurl.com/4zhxba27