A Randomized Phase III Study of Rocapuldencel-T an Autologous Dendritic Cell–Based Vaccine, in Combination with Sunitinib as First- line Therapy in Patients with Groups Metastatic Clear-Cell Renal Cell Carcinoma

Overall Survival

Overall Survival

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Summary

This trial aims to investigate the safety and efficacy of a combination therapy of Rocapuldencel-T plus sunitinib in patients diagnosed with metastatic renal cell carcinoma (mRCC). Rocapuldencel-T did not improve OS in patients treated with combination therapy, although the induced immune response correlated with OS.

Patients characteristics

462 Patients were newly diagnosed with advanced disease histologically assessed as renal cell carcinoma (RCC), with predominantly clear cell histology. Karnofsky performance status score of <80%, time from initial diagnosis to treatment of <1 year and life expectancy of 6 months or greater, hemoglobin level below the lower limit of the normal range, corrected serum calcium concentration of >10 mg per deciliter, absolute neutrophil count above the upper limit of normal (ULN) range, and a platelet count above the ULN range.

Methodology

Autologous tumor total RNA was isolated from standard nephrectomy (partial or cytoreductive nephrectomy) tumor tissue confirmed having predominantly clear cell histology. Per protocol, after excision tissue was placed on ice and immediately placed in RNA preservative to maintain RNA integrity. CD40L RNA was manufactured using in vitro transcription and a post- transcriptional capping method. DC product was matured from monocytes isolated from patient leukapheresis by elutriation and co-electroporated with amplified tumor RNA and CD40L RNA using a post-maturation electroporation protocol. Final product was formulated as 1.4×107 DC/0.7mL in 80% autologous plasma, 10% dextrose (50% w/v), and 10% DMSO and cryopreserved in liquid nitrogen vapor phase.

Treatment

Rocapuldencel-T was administered into a single lymph node basin as three intradermal injections of 0.2 mL each (0.6 mL total volume). Rocapuldencel-T dosing was initiated after completion of at least one 6-week sunitinib cycle followed by one dose every 3 weeks for a total of five doses (induction phase). Doses were administered through 48 weeks irrespective of disease progression, unless unacceptable toxicity occurred, or per patient/physician decision. A total of 462 patients were randomized 2:1 to receive either Rocapuldencel-T plus SOC treatment or SOC treatment alone. For both groups, SOC treatment was initiated with sunitinib, administered per current labeling for mRCC.

Results

Clinical outcomes and safety assessment
The ITT population included all randomized patients (n=462).For the primary endpoint, median overall survival (OS) in the combination group was 27.7 months (95% CI, 23.0–35.9) and 32.4 months (95% CI, 22.5, -) in the SOC group with an unadjusted HR of 1.10 (95% CI, 0.83–1.46) and a HR of 1.06 (95% Cl, 0.79–1.40) after adjustment for randomization stratification factors. PFS for the ITT population was 6.0 months (95% CI, 5.8-6.7) in the combination group and 7.83 (95% Cl, 5.87–9.3) in the SOC group with a HR of 1.15 (95% Cl, 0.92– 1.44) in the ITT population.
The mITT population (n=409) included all randomized patients who received at least 1 or more doses of Rocapuldencel-T (n=268) or at least 1 or more doses of sunitinib (n=141). Median OS in the combination group was 30.4 months (95% CI, 25.8-) and 32.5 months (95% CI, 23.0-) in the SOC group with an unadjusted HR of 0.97 (95% CI, 0.72–1.33), and a HR of 0.95 (95% CI, 0.70– 1.29) after adjustment for randomization stratification factors.
There was a total of 9 (2.9%) CRs in the combination group and 3 (1.9%) in the SOC group; the number of PRs in the two groups was 122 (39.7%) and 58 (37.4%), respectively. The ORR was similar between the two groups, 42.7% (95% CI, 37.1–48.4) in the combination group and 39.4% (95% CI, 31.6–47.5) in the SOC group.

Conclusion

Rocapuldencel-T did not improve OS in patients treated with combination therapy, although the induced immune response correlated with OS.

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Scientific article publishing date 7/2/2020

Immucura identifier BSC21_063EN

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