IND-213 -> Aware-1 -> Bracelet-1 - BC Study flow rationaleFrom a posting on Yahoo.com message board which summarizes the clinical trials that flowed from the IND-213 study conducted by the Canadian Cancer Trials Group (CCTG). The CCTG found an unexpected 7 month OS in breast cancer patients when treated with pelareorep in combination with standard therapy consisting of chemotherapy compared to chemotherapy alone. This findings led to the Aware-1 study which in-turn has led to the Bracelet study.
This is a summary that was posted on ONCY's Yahoo.com message board:
"The AWARE-1 study (Aleix Prat et.al.) that followed IND-213 concluded the following in the poster entitled: “A window-of-opportunity Study with atezolizumab and the oncolytic virus pelareorep in early Breast Cancer (REO-027, AWARE-1)”, Prat et al, ESMO Breast Cancer, 2020
1. The degree of viral replication was consistent with changes in CelTIL and within immunological change in the TME, mainly CD8 T-cell infiltration and PD-L1 expression.
2. Preliminary data from the first six patients in AWARE-1 demonstrate pela-mediated priming of an adaptive immune response, helping to validate our hypothesis that the extended OS observed in our prior mBC study can be attributed to pela-mediated T-cell priming
3. Following initial treatment (~3 weeks), peripheral T-cell clonality may be correlated with changes in CelTIL and clinical response as seen in prior studies (Mahalingam et al. Clinical Cancer Research (2020) 26, 71-81.)
- Mahalingam et al concluded : "Pelareorep in combination with chemotherapy and pembrolizumab in patients with advanced, pretreated PDAC was well-tolerated and showed prolonged efficacy in three patients. Viral immunomodulation was evident, with early and durable clones associated with long-term outcomes, but given our small sample size, this should be examined as a dynamic predictive biomarker in future studies with oncolytic viruses." - which was the premise of the AWARE-1 biomarker study. "
......... And the purpose of the Bracelet-1 study is to trial pelareorep in combination with an immune checkpoint inhibitor (avelumab).
BRACELET-1 is an open-label, phase 2, randomized study in patients with HR+/HER2-, endocrine-refractory metastatic breast cancer being conducted under a co-development agreement with Merck KGaA, Darmstadt, Germany and Pfizer. PrECOG LLC, a leading cancer research network, is managing the study. The study is taking place at 20 trial sites with enrollment of 45 patients randomized into three cohorts. A three patient safety run-in will be conducted with patients receiving pelareorep, paclitaxel, and avelumab prior to randomization. The three cohorts will be treated as follows: - Cohort 1 (n=15): paclitaxel
- Cohort 2 (n=15): paclitaxel + pelareorep
- Cohort 3 (n=18): paclitaxel + pelareorep + avelumab (Bavencio®)
Apart from breast cancer, ONCY's overall stated clinical development plan is the following:
'Our clinical development plan is based on pelareorep’s broad applicability to boost the effectiveness of a range of immunotherapies – with an immediate focus on checkpoint inhibitors – across multiple cancer indications. The primary objective is to obtain regulatory approval for pelareorep as quickly as possible and is based on our compelling metastatic breast cancer survival data, our synergies with checkpoint approved inhibitors and our biomarker. The second objective is to expand pelareorep into commercially valuable new treatment areas including other immunotherapy agents in collaboration with pharmaceutical partners.
We are excited to work with Pfizer, Merck KGaA, Merck, Bristol-Myers Squibb, Roche, and Incyte with their checkpoint inhibitors, and look forward to developing our programs to evaluate the efficacy and safety in our clinical studies targeting metastatic breast cancer, early stage breast cancer, multiple myeloma and gastrointestinal cancer, including pancreatic, colorectal, and anal. '