A randomized phase II study of pelareorep and docetaxel or docetaxel alone in men with metastatic castration resistant prostate cancer: CCTG study IND 209

Abstract

BackgroundPelareorep is an oncolytic virus with activity in many cancers including prostate. It has in vitro synergism with microtubule-targeted agents. We undertook a clinical trial evaluating pelareorep in mCRPC patients receiving docetaxel.Patients and MethodsIn this randomized, open-label phase II study, patients received docetaxel 75mg/m2 on day 1 of a 21-day cycle and prednisone 5mg twice daily, in combination with pelareorep (arm A) or alone (arm B). The primary endpoint was 12 weeks lack of disease progression rate (LPD).ResultsEighty-five pts were randomized. Median age was 69, ECOG performance status was 0/1/2 in 31%/66%/3% of patients. Bone/regional lymph node/liver metastases were present in 98%/24%/6%. The median prognostic score was slightly higher in Arm A (144 vs. 129 p= 0.005). Adverse events were as expected but more prevalent in arm A. The 12-week LPD rate was 61% and 52.4% in arms A/B (p=0.51). Median survival was 19.1 on Arm A and 21.1 months on Arm B (HR 1.83; 95% CI 0.96 to 3.52; p=0.06). No survival benefit of pelareorep was found.ConclusionPelareorep with docetaxel was tolerable with comparable LPD in both arms but response and survival were inferior and so this combination does not merit further study.

Efficacy and Safety of Oncolytic Viruses in Randomized Controlled Trials: A Systematic Review and Meta-Analysis

“…Blinding was not performed because of the moral risk associated with the sham injection. In some RCTs [ 19 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ], non-blinding had no significant effect on the efficacy or safety of oncolytic viruses; hence, they were judged as a low-risk factor.…”

“…Oncolytic RNA viruses include pelareorep and NTX-010. Pelareorep is a human reovirus type 3 Dearing strain, which contains live, replication-competent reovirus, and has specific oncolysis with an activated Ras pathway [31,33]. Direct oncolysis of pelareorep led to release of "danger signals", such as soluble tumor-associated antigens, viral pathogen-associated molecular patterns, and cell-derived damage-associated molecular patterns [16,40].…”

“…In this meta-analysis, we included the following viruses: T-VEC (herpes virus) [ 26 , 27 ], pelareorep (reovirus) [ 28 , 29 , 30 , 31 , 32 , 33 ], NTX-010 (seneca valley virus; picornavirus) [ 19 ], Ad5-yCD/ mut TK SR39 rep -ADP (adenovirus) [ 34 ], and pexastimogene devacirepvec (Pexa-Vec; poxvirus) [ 35 ]. We first evaluated the efficacy of oncolytic virus from objective response rate (ORR), overall survival (OS), and progression-free survival (PFS); then we analyzed severe adverse events (grade ≥3) and detailed adverse events (AEs).…”

Fugitives on the run: circulating tumor cells (CTCs) in metastatic diseases

“…In addition to use as a prognostic biomarker, CTC enumeration is being used as an exploratory indicator of efficacy and a measurement of treatment response [42–44]. A drop-off in CTC counts showed promise as an early efficacy endpoint in a study observing cabazitaxel response in metastatic castration resistant prostate cancer (mCRPC) patients with docetaxel resistance [42].…”

Examination of viral infection and host response to define therapeutic potential of oncolytic mammalian orthoreovirus

“…Men were treated with docetaxel or MRV and docetaxel, but unfortunately patients treated with MRV and docetaxel were not shown to benefit more than those treated with docetaxel alone. While MRV therapy was shown to be safe and tolerable, similar to other clinical trials, it did not improve overall survival (146). This suggests that the patients selected for this clinical trial were not a good fit for MRV therapy, and future research into MRV and PCa can provide insight into what kind of tumor environments or tumor genetic profiles might respond favorably to MRV therapy in PCa.…”