Vaccination of Metastatic Renal Cancer Patients with MVA-5T4: A Randomized, Double-Blind, Placebo-Controlled Phase III Study

Abstract

Purpose: The TroVax Renal Immunotherapy Survival Trial was a randomized, placebo-controlled phase III study that investigated whether modified vaccinia Ankara encoding the tumor antigen 5T4 (MVA-5T4) prolonged survival of patients receiving first-line standard-of-care (SOC) treatment for metastatic renal cell cancer.Experimental Design: Patients with metastatic clear cell renal cancer, prior nephrectomy, and good or intermediate prognosis were randomized 1:1 to receive up to 13 immunizations of MVA-5T4/placebo in combination with either sunitinib, interleukin-2 or interferon-α. The primary end point was overall survival. Secondary end points included progression-free survival, overall response rate, and safety.

Tumor Biology and Prognostic Factors in Renal Cell Carcinoma

“…This surface receptor is an ideal DC target given its capacity for binding and endocytosis of materials [43]. Vaccinia-based approaches were also recently investigated [44,45]. Amato et al [44] used an attenuated vaccinia virus designed to deliver the tumor antigen 5T4, an oncofetal protein expressed in most RCCs.…”

“…Vaccinia-based approaches were also recently investigated [44,45]. Amato et al [44] used an attenuated vaccinia virus designed to deliver the tumor antigen 5T4, an oncofetal protein expressed in most RCCs. In a phase III, randomized, double-blind study of patients with mRCC, MVA-5T4 or placebo was administered to patients in combination with standard-of-care IL-2, IFN-␣, or sunitinib.…”

Carcinogenesis of renal cell carcinoma reflected in HLA ligands: A novel approach for synergistic peptide vaccination design

“…These include unspecific interleukin-2 (IL-2) therapy and specific strategies such as autologous vaccines and dendritic cell-based as well as RNA-or peptide-based approaches. [4][5][6][7][8] Recently, in a multipeptide vaccination phase II trial, overall patient survival was prolonged by the induction of specific T cell response. 9 Although a corresponding phase III trial did not confirm these results (data not published) other vaccination trials, e.g., in head and neck squamous cancer, showed induction of T cell response and prolonged overall survival.…”

Trial Watch: Therapeutic vaccines in metastatic renal cell carcinoma

“…44 Another promising new approach is adoptive cell therapy using engineered T-cell Chimeric Antigen Receptor (CAR). 45 Clinical trial results for therapeutic RCC vaccines We reviewed 6 clinical trials of RCC-specific therapeutic vaccines administered in an adjuvant or a metastatic setting: three completed phase III trials (Reniale, [46][47] Trovax, [48][49][50] and Vitespen 51 ) and three phase II trials (TG4010, 52 AGS003, [53][54] and IMA901 21 ), as well as a meta-analysis of dendritic cell (DC)-based vaccines in mRCC 55 ( Table 1). The publications were retrieved from a Medline search (from january 2004 to november 2014).…”

“…56 The TRIST phase III trial of MVA-5T4 in combination with IFNa, IL2 or sunitinib as first-line mRCC therapy did not meet its objective of a significant increase in OS. 48 However, patients with a vaccineinduced antigen-specific immune response did show higher OS, and those with a good MSKCC prognostic score receiving MVA-5T4/IL2 had significantly better OS than patients on placebo/IL2 ; (Hazard Ratio (HR): 0¢54 [0¢30-0¢98], p D 0¢046). As MVA-5T4 targets a single TAA, each patient has to be evaluated for tumor TAA expression and for any preexisting specific immune response.…”