Abstract 1642: Evaluation of ENMD-2076 in combination with anti-PD1 in syngeneic cancer models
Bibliographic record
Abstract
Abstract ENMD-2076 is a clinical stage compound with potent activity towards Aurora A and angiogenic kinases. ENMD-2076 has shown promising activity in multiple Phase 1 clinical trials, as well as in a Phase 2 trial in advanced ovarian cancer. ENMD-2076 is currently the subject of several ongoing Phase 2 clinical trials including fibrolamellar carcinoma, triple-negative breast cancer (TNBC), advanced/metastatic soft tissue sarcoma (STS), and advanced ovarian clear cell carcinomas (OCCC). ENMD-2076 has been developed to date as a single agent, however ENMD-2076 inhibits a spectrum of targets including Aurora A, FAK, CSF1R, c-Kit, and KDR, that are potentially involved in immune evasion mechanisms. These kinases have been shown in published studies, when inhibited, to enhance or augment the activity of immune checkpoint inhibitors such as anti-PD1. A study was thereby conducted in syngeneic models to determine the utility of ENMD-2076 combined with immune checkpoint inhibition as a rational strategy for cancer therapy. The study evaluated the efficacy of ENMD-2076 administered daily by oral gavage in the MC38 and CT26 colon cancer models, alone and in combination with an anti-PD1 antibody. Xenografts were established in the appropriate mouse strain (C57BL/6 and BALBc, respectively) by the subcutaneous inoculation of MC38 or CT26 cells into the right flank of female mice. Treatment was initiated 7 days following inoculation when tumor volumes had reached a mean volume of approximately 85 mm3. All treatments were well tolerated, with no significant body weight loss seen during either study. While CT26 tumors were relatively refractory to single agent ENMD-2076, tumor regression was observed in several MC38-bearing animals suggesting an immune activating mechanism. In both models a trend was observed for an augmentation of anti-tumor response in combination relative to single agent ENMD-2076 and anti-PD1 alone. Further studies to evaluate mechanism and an assessment of re-challenge experiments in animals exhibiting complete regression of tumors will be discussed. These studies support the further evaluation of ENMD-2076 in combination with immune checkpoint inhibition as a strategy for cancer therapy. Citation Format: Graham C. Fletcher, Reza Kiarash, Mark R. Bray, Amanda S. Hu, Ken K. Ren. Evaluation of ENMD-2076 in combination with anti-PD1 in syngeneic cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1642. doi:10.1158/1538-7445.AM2017-1642
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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".