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AUSTIN, Texas -- A dendritic-cell immune primer failed to meet survival endpoints in a randomized trial of high-risk synchronous metastatic renal cell carcinoma (mRCC) but nonetheless showed evidence of activity.

The 18-month overall survival (OS) rate was 63% with preoperative sunitinib (Sutent) plus ilixadencel versus 66% with sunitinib alone. Thereafter, the survival curves separated in favor of the combination, ending in a median OS of 35.6 months with the addition of ilixadencel and 25.3 months with single-agent therapy.

All five patients who achieved complete response (CR) with the combination remained alive at last follow-up, whereas the only patient with sunitinib-induced CR had died, reported Börje Ljungberg, MD, PhD, of Umeå University in Sweden, here at the International Kidney Cancer Symposium.

"To us the most interesting finding was that the five complete responses with the cellular therapy continued, whereas the response with sunitinib alone did not," said Ljungberg. "The prolonged responses and the [improvement in survival over time] suggest the experimental treatment has an immunologic effect, not necessarily by itself, but in stimulating the immune system to increase the activity of the other therapy."

Patients with synchronous mRCC have metastatic disease at diagnosis, which confers a poor prognosis. The advent of targeted tyrosine kinase inhibitors (TKIs), such as sunitinib, has helped improve the outlook for the disease, and immunotherapy has led to further improvement. Nonetheless, new and novel therapies and strategies are needed to continue the progress and to offer patients options when existing therapies fail, Ljungberg and colleagues noted in their poster presentation.

Ilixadencel is an (vaccine) constructed from allogeneic monocyte-derived dendritic cells. Developed for intratumoral injection, the cellular therapy induces recruitment and activation of endogenous immune cells, leading to cross-presentation of tumor antigens by co-recruited dendritic cells.

In separate phase I clinical trials, ilixadencel demonstrated activity in TKI-resistant and in advanced . A first-in-human trial in patients with demonstrated the safety of ilixadencel and produced evidence of antitumor immune response in patients receiving standard therapy.

Ljungberg presented results from a phase II randomized trial evaluating sunitinib with or without ilixadencel as preoperative therapy for nephrectomy candidates with synchronous mRCC. Patients were randomized 1:2 to sunitinib alone or preceded by two injections of ilixadencel into the primary tumor 2 weeks apart, followed by surgery in all cases.

The primary endpoints were 18-month OS and median OS, and the key secondary endpoint was objective response rate (ORR), as assessed up to 18 months. The primary analyses included 88 randomized patients. The study population had a median age of 63-64, and men accounted for about three fourths of all patients.

The study had a median follow-up of 36.2 months. The addition of ilixadencel did not improve 18-month OS (95% CI 49-74% vs 46-80%, P=0.30) or median OS (HR 0.73, 95% CI 0.42-1.27). The addition of ilixadencel led to an ORR of 42.2% (including five CRs) versus 24% and one CR with single-agent sunitinib.

As , rates of all-grade adverse events (AEs) were similar (93% with ilixadencel vs 90% with single-agent sunitinib). The most common AEs in both treatment arms were fatigue, nausea, and diarrhea. The most commonly observed grade ≥3 AEs in the ilixadencel group were hypertension (6.9%), anemia (5.3%), and asthenia, pyrexia, and vomiting (3.5% each). The most common grade ≥3 AEs with sunitinib alone were diarrhea, asthenia, and hypercalcemia (6.7% each).

Poster session moderator Shawn Dason, MD, of Ohio State University in Columbus, asked whether ilixadencel might also enhance the antitumor activity of immune checkpoint inhibitors. Ljungberg said the issue has not been addressed to his knowledge, adding that the cellular therapy's developer, Mendus AB (formerly Immunicum AB), has discontinued enrollment in clinical trials of ilixadencel.

"That's unfortunate because these are interesting results," said Dason. "It would be interesting to see what the effects [of ilixadencel] would be with immunotherapy and other treatment."

Ljungberg pointed out that ilixadencel represents an off-the-shelf treatment strategy "so anyone could develop this."

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