FDA Grants RMAT Designation to Ilixadencel in Metastatic RCC

The FDA has granted a Regenerative Medicine Advanced Therapy (RMAT) designation to ilixadencel, as treatment of metastatic renal cell carcinoma (RCC), Immunicum AB announced in a press release.¹

“We are very excited to have received the RMAT designation for ilixadencel in kidney cancer as it recognizes both the potential of our novel therapeutic approach as well as the clear need for viable therapies to address this difficult-to-treat disease. As a designation similar to the FDA’s Breakthrough Therapy Designation, we will now also have the opportunity to receive direct guidance from the FDA which will inform key development decisions and ultimately bring us closer to delivering ilixadencel to patients in need,” commented Alex Karlsson-Parra, chief executive officer of Immunicum.

The RMAT decision was based on previously reported data from the phase II MERECA study (NCT02432846), which is evaluating the safety and efficacy of ilixadencel in combination with sunitinib (Sutent) in newly diagnosed patients with metastatic RCC.

In the open-label, randomized, controlled multicenter study, 86 patients were enrolled, 56 of whom received ilixadencel plus sunitinib and 30 of whom received sunitinib alone. The updated results presented at the 2020 ASCO-SITC Clinical Immuno-Oncology Symposium showed a separation in the survival curves in favor of the ilixadencel arm. Overall, the rate of survival was 54% in the ilixadencel group compared with 37% in the sunitinib group. Data to determine the median overall survival (OS) in the study had not yet matured at the time of cutoff.The confirmed objective response rate (ORR) with ilixadencel was 42.2% versus 24.0% in the control arm.²

Earlier data from this study showed an objective ORR of 44% with ilixadencel, and 48% suntinib, which included complete response in 11% of patients and 4% of patients, respectively.³

Patients in the study were randomized 2:1 to receive either ilixadencel 10 milj cells vaccination of ilixadencel for 14 days plus sunitinib of sunitinib alone. Both arm also underwent nephrectomy. In the ilixadencel combination arm, ilixadencel was administered prior to surgery, and sunitinib was administered after surgery. In the monotherapy, treatment also occurred after surgery.²

The co-primary end points of the MERECA study were OS and the overall 18-month survival rate from randomization in different subgroups of patients with metastatic RCC. The key secondary end points were the frequency of adverse events, progression-free survival, the proportion of patients with an ORR from the start of sunitinib and DOR in each group, and time to progression.

Eligible patients were required to be newly diagnosed with histologically or cytologically confirmed RCC with at least 1 metastasis ≥10 mm for which complete mastectomy is not planned, as determined by a CAT scan. The primary tumor diameter in these patients must have been at least 40 mm. Patients were also required to have adequate hematologic values, creatinine and bilirubin values, and be candidates for first-line therapy with sunitinib initiated for 5 to 8 weeks after nephrectomy.

The study excluded patients who had a history of invasive cancer within 5 years of study screening with the exception of situ carcinoma or nonmelanoma skin cancer. In addition, individuals who had prior systemic antitumor therapy within 28 days before screening; and individuals with a poor performance status, certain infections, and comorbidities were excluded from the study.

With an RMAT designation, the off-the-shelf cell-based cancer immunotherapy, ilixadencel, the developer can receive direct advice from the FDA around further development of the drug to bring it closer to FDA approval.¹

_References:

_{1. Immunicum AB (publ) receives Regenerative Medicine Advanced Therapy designation from fda for ilixadencel in kidney cancer [news release]. Stockholm, Sweden: Immunicum AB; May 6, 2020. https://bit.ly/2zpyx64. Accessed May 8, 2020.}

_{2. Immunicum AB (publ) presents updated data from phase ii mereca trial of ilixadencel in kidney cancer at ASCO-SITC Clinical Immuno-Oncology Symposium [news release]. February 6, 2020. bit.ly/2wopYaL. Accessed May 8, 2020.}

_{3. Lindskog M, Laurell A, Kjellman A, et al. A randomized phase II study with ilixadencel, a cell-based immune primer, plus sunitinib versus sunitinib alone in synchronous metastatic renal cell carcinoma. J Clin Oncol. 2020;(suppl 5;abstr 11). doi: 10.1200/JCO.2020.38.5_suppl.11.}