Abstract OT-13-02: Bracelet-1 (pre0113): A study to assess overall response rate by inducing an inflammatory phenotype in metastatic breast cancer with the oncolytic reovirus pelareorep in combination with anti-PD-L1 avelumab and paclitaxel
Bibliographic record
Abstract
Abstract Background: A randomized phase 2 study with the intravenously delivered oncolytic virus, pelareorep, in combination with paclitaxel (PTX) demonstrated a statistically significant improvement in overall survival (OS) from 10.4 months with PTX alone to 17.4 months with pelareorep + PTX (HR 0.65, 80% CI 0.46-0.91, P = 0.1) in metastatic breast cancer (mBC) patients. The greatest benefit in OS was seen in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) disease (Bernstein et al, 2018). However, pelareorep + PTX did not improve progression-free survival or objective response relative to PTX alone, suggesting a late-onset adaptive immune response. A subsequent window of opportunity study in early breast cancer has shown that pelareorep can indeed promote an adaptive immune response in breast cancer tissue, enhancing CD8+ T cell infiltration and upregulating PD-L1 expression, correlating with high levels of viral replication in HR+/HER2- tumor tissue (Manso et al, 2020). Moreover, high levels of peripheral T cell clonality (PTCC) have been identified as a candidate blood-based on-treatment biomarker for pelareorep therapy, further highlighting the role of an adaptive immune response in driving pelareorep mediated efficacy (Mahalingam et al, 2020; Manso et al, 2020). Thus, BRACELET-1 will test the hypothesis that pelareorep mediated priming of an adaptive immune response will be synergistic with checkpoint blockade therapy in HR+/HER2- mBC. Moreover, BRACELET-1 will further assess PTCC as an on-treatment biomarker. The overall goal of this study is to expand the number of mBC patients who can benefit from better immunotherapy. Study Design: This is an open-label randomized phase 2, three-cohort study in HR+/HER2- mBC. Patients must be refractory to endocrine therapy and have received prior treatment with a CDK4/6 inhibitor. Study cohorts include: Cohort 1, a control group receiving PTX (n = 15); Cohort 2, treatment with pelareorep added to PTX (n = 15); Cohort 3, treatment with pelareorep, PTX, and avelumab (n = 18). The study includes a three patient safety run-in for Cohort 3. Specific aims: (1) Evaluation of efficacy in terms of overall response rate (ORR) at week 16, according to RECIST v1.1; (2) Examination of the safety of the study treatments; and (3) Assessment of key biomarkers, such as PTCC which will be correlated to treatment efficacy. Present accrual and target accrual: The study is currently enrolling and is registered on clinicaltrials.gov: NCT04215146. Current enrollment = 2; Target enrollment = 48. This study is conducted through PrECOG, LLC and Oncolytics Biotech, Inc. Study contact information: PrE0113@precogllc.org. Citation Format: Kathy Miller, Fengmin Zhao, Amy Clark, Grey Wilkinson, Rita Laeufle, Antonio Wolff. Bracelet-1 (pre0113): A study to assess overall response rate by inducing an inflammatory phenotype in metastatic breast cancer with the oncolytic reovirus pelareorep in combination with anti-PD-L1 avelumab and paclitaxel [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-13-02.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".