Abstract OT2-25-01: Irene study: Phase 2 study of Incmga00012 and the oncolytic virus pelareorep in metastatic triple negative breast cancer
Bibliographic record
Abstract
Abstract Background: Triple negative breast cancer (TNBC) is an aggressive subtype accounting for 15% of all breast cancer subtypes. It is characterized by larger tumor size, higher grade, early peak of recurrence, and a worse 5-year overall survival rate compared to other breast cancer subtypes. Treatment with immunotherapy has been shown to be beneficial in PD-L1 positive patients in the metastatic setting. Priming the tumor environment can upregulate PD-L1 expression. Pelareorep, a proprietary isolate of the unmodified replication competent reovirus type 3 Dearing (T3D) strain, a non-enveloped reovirus has been shown to upregulate PD-L1 expression in tumor and inflammatory cells and promote a favorable CD8:regulatory T cell ratio indicating a less immunosuppressive tumor microenvironment. Retifanlimab (INCMGA00012) is PD-1 inhibitor currently in development. A phase 2 study is currently underway studying the combination with the rationale that the administration of pelareorep will prime the tumor microenvironment for enhanced tumor response to PD-1 inhibitor retifanlimab. Trial design: This is a phase II multi-site single-arm clinical trial to study the combination of PD-1 inhibitor retifanlimab and the oncolytic virus pelareorep in patients with metastatic triple negative breast cancer. Eligible patients will receive pelareorep 4.5x1010 TCID50/day, on Days 1, 2, 15 and 16 and retifanlimab 500 mg on day 3 of every 28-day cycle. Patients will be monitored clinically and radiologically for response to treatment. Tumor tissue, stool and blood samples will be collected during treatment to evaluate changes in PD-L1 expression, gut microbiome and inflammatory cells induced by the study drugs. (ClinicalTrials.gov Identifier: NCT04445844) Eligibility criteria: Premenopausal/postmenopausal women with metastatic TNBC who have previously received 1-2 prior lines of chemotherapy in the metastatic setting are eligible for the study. They must have adequate performance status (ECOG PFS 0-2). Specific aims: Primary endpoint will be objective response rate (ORR) and safety, determined by the number, frequency, duration, and severity of AEs using CTCAE v5.0. The Secondary end-points will be progression free survival (PFS), overall survival (OS), duration of response (DOR) and quality of life measures using EORTC QLQ-C30. Statistical methods: Simon’s optimal 2-stage design will be used to calculate sample size. In the first stage, 14 patients will be accrued. If there are 1 or fewer responses in these 14 patients, the study will be stopped. Otherwise, 11 additional patients will be accrued for a total of 25. The null hypothesis will be rejected if 4 or more responses are observed in 25 patients. The first 6 patients will be enrolled in a staggering interval for the safety run-in phase of the study. Accrual: The study is currently enrolling patients at Rutgers Cancer Institute of New Jersey and Ohio State University Comprehensive Cancer Center. There are no safety signals with the combination in patients who have received both drugs to date. Citation Format: Mridula George, Nicole Williams, Coral Omene, Nancy Chan, Shou-En Lu, Danielle Tang, Grey Wilkinson, Shridar Ganesan, Deborah Toppmeyer. Irene study: Phase 2 study of Incmga00012 and the oncolytic virus pelareorep in metastatic triple negative breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-25-01.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| 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".