Frontline Ilixadencel Plus Sunitinib Demonstrates Further Survival Benefit in mRCC

Frontline ilixadencel (Intuvax) in combination with sunitinib (Sutent) as utilized in newly diagnosed patients with metastatic renal cell carcinoma (mRCC) in the phase 2 MERECA clinical trial has updated survival data, which indicates continued survival benefit with the combination over sunitinib alone. The results were announced in a press release issued by the developer of ilixadencel, Immunicum AB.¹

“As our largest and longest study, the phase 2 MERECA trial continues to give us insight into the potential efficacy of ilixadencel in combination with standard-of-care in patients with metastatic tumors. As such, we are encouraged that the data at this stage show that only two injections of ilixadencel continue to have an impact on survival of patients as the median Overall Survival of that group has not yet been reached,” said Alex Karlsson-Parra, MD, PhD, associate professor of Uppsala University and chief scientific officer and interim chief executive officer of Immunicum AB, in a statement.

MERECA included 88 patients who were randomized 2:1 to receive either ilixadencel plus sunitinib (n = 56) or sunitinib alone (n = 30), and patients in each arm also underwent nephrectomy. Ilixadencel was administered at least 14 days before surgery, and sunitinib was administered post-surgery. Patients were evaluated for the coprimary end points of overall survival (OS), and the 18-month survival rate from randomization in the overall population and subgroup populations. The secondary end points include the frequency/proportion of adverse events, progression-free survival, objective response rate, time to progression, and the relative number of tumor CD8-positive T cells in the resected primary tumor compared with the related number of infiltrating CD8-positive T cells.

The median OS was reached at 25.3 months in the control group compared to the ilixadencel plus sunitinib, in which the median OS has not yet been reached. Data are still maturing for the ilixadencel arm. What is known is that 43% of patients in the ilixadencel are stills alive as of the data cutoff compared with 33% of the sunitinib only arm. In addition, patients in the ilixadencel arm who achieved a complete response (CR) were also still alive in the follow-up analysis. The patients who achieved a CR in the sunitinib only group died during follow-up.

The Kaplan-Meier survival curves of the study data reportedly continue to separate in favor of the addition of ilixadencel, according to the latest data from August. The curve separation is in line was projections from prior follow-ups.

“As the data continue to mature, we are able to further analyze which patients most benefit from ilixadencel and design our future studies to maximize our understanding of the therapeutic potential for patients,” said Karlsson-Parra.

Previously, it was announced that the rate of survival with the ilixadencel combination was 54% versus 37% with sunitinib alone. The confirmed ORR was 42% with the addition of ilixadencel versus 24% with sunitinib monotherapy. In terms of the duration of responses, responses to ilixadencel plus sunitinib lasted for a median of 7.1 months compared with 2.9 months in the sunitinib monotherapy arm. The median PFS observed was 11.8 months with the combination versus 11.0 months with sunitinib alone.²

MERECA was an open-label, randomized, controlled multicenter study (NCT02432846). To be eligible to enroll, patients were required to have newly diagnosed disease by histology or cytology, planned resection of the primary tumor, a primary tumor diameter greater than 40mm, adequate hematology parameters, and must have been candidates for frontline treatment with sunitinib administered 5 to 8 weeks following nephrectomy. Individuals with a life expectancy below 4 months, those with central nervous system metastasis, active autoimmune disease, and other comorbidities that may have interfered with the study treatment were ineligible to enroll in MERECA.¹

Ilixadencel is an off-the-shelf cell-based cancer immunotherapy. In addition to being assessed as treatment of patients with mRCC, it has also been studied in hepatocellular carcinoma and gastrointestinal stromal tumors in combination with the tyrosine kinase inhibitor sunitinib, the multikinase inhibitor regorafenib (Stivarga), and the checkpoint inhibitor pembrolizumab (Keytruda). With the completion of the MERECA study, ilixadencel is moving forward in development to confirm the efficacy and safety observed in these various tumor types.

_References:

_{1. Immunicum AB (publ) announces update on survival data from phase ii mereca trial of ilixadencel in kidney cancer. News release. Immunicum AB. August 18, 2020. Accessed August 19, 2020. https://bit.ly/325137T}

_{2. Immunicum AB (publ) presents updated data from phase II MERECA trial of ilixadencel in kidney cancer at asco-sitc clinical immuno-oncology symposium. New release. Immunicum AB. February 6, 2020. Accessed August 18, 2020. https://bit.ly/2wopYaL}