Therapeutics- Systemic (Ablation, Interventional Radiology, Medical Oncology, Radiation Therapy, Surgery, Urology)

37: A randomized phase 2 study with a cell-based immune primer plus sunitinib versus sunitinib aone in metastatic Renal Cell Carcinoma.

Location: Poster Hall, Board D5

Width:

Kaplan-Meier estimate of survival for all patients

Survival probability (all patients) is displayed graphically using Kaplan-Meier, including summaries of number of events (marked as a black star) and censored observations (marked as a black circle). The red line represents ilixadencel and sunitinib strata (high and intermediate-risk) and the blue line represents sunitinib strata (high and intermediate-risk). The patients at risk are indicated below figure for each stratum.

Poster Presenter(s)

Börje Ljungberg, MD, PhD

Professor of Urology
Umeå University
Umeå, Sweden

Background: The prognosis in patients with synchronous metastatic renal cell carcinoma (mRCC) remains poor. Despite prosperous improvements with single agent tyrosine kinase inhibition (TKI) and additionally effects by immune checkpoint inhibitor (ICI) combinations (ICI/ICI or ICI/TKI), the treatments are insufficient. Innovative treatment options can be beneficial.

Methods: A randomized (2:1) phase 2 multicenter trial enrolled 88 patients with synchronous mRCC to treatment with the combination of two doses of allogeneic monocyte-derived dendritic cells (ilixadencel) and sunitinib (ILIXA/SUN) (58 patients) or sunitinib monotherapy (SUN) (30 patients). The ilixadencel was administrated intratumorally two weeks apart, followed by nephrectomy and sunitinib. The experimental arm was compared with nephrectomy and sunitinib monotherapy. Primary endpoints were 18-month survival rate and overall survival (OS). A secondary endpoint was objective response rate (ORR) assessed up to 18 months post enrollment. Statistic evaluations included Kaplan-Meier, log-rank tests, Cox regression and stratified Cochran–Mantel–Haenszel tests.

Results: Median OS was 35.6 months in the ILXA/SUN arm versus 25.3 months in the SUN arm (HR 0.73, 95%CI:0.42-1.27), while the 18-month OS rate was 63% and 66% in the ILIXA/SUN and SUN arms, respectively. Confirmed ORR in ILIXA/SUN arm was 42.2% (19/45), including 3 patients with complete response (CR), versus 24.0% (6/25) in the SUN arm (p=0.13) without any CR. At the last scheduled imaging follow-up at 18 months two additional patients in the ILIXA/SUN arm (total 5 of 45 = 11%) had developed CR and one SUN patient (1/25). The five ILIXA/SUN patients who achieved CR, were all alive at the latest survival follow up, while the SUN CR patient had died.

Conclusions: The study failed to meet its primary endpoints. However, ilixadencel in combination with sunitinib was associated with a numerically higher response rate, including longstanding CRs, compared with sunitinib monotherapy, suggesting an immunologic effect of the experimental treatment.