Abstract B55: A study of REOLYSIN in combination with gemcitabine in patients with advanced pancreatic adenocarcinoma.
Bibliographic record
Abstract
Abstract Background: Pancreatic cancer (Pca) continues to have a dismal prognosis and very little progress has been made in finding new efficacious treatments. Oncolytic viruses have demonstrated cytotoxic effect in several tumor xenografts, particularly in cells with RAS pathway activation. REOLYSIN (Reovirus serotype 3) has shown extensive antitumor activity in preclinical models, as well as synergistic activity with cytotoxics including gemcitabine in various cancers. Several phase 1 and 2 clinical trials demonstrated tolerability and promising activity of REOLYSIN administered as a single agent in patients with solid tumors. Due to the high frequency of Kras pathway activation in Pca, we hypothesized that REOLYSIN may enhance the anticancer activity of chemotherapy in this tumor type. Therefore, this study was initiated to test the safety and efficacy of a combination of REOLYSIN with gemcitabine in previously untreated patients with Pca. Methods: Patients with diagnosis of chemotherapy-naïve, surgically unresectable or metastatic Pca are eligible for the study. The primary objective is Clinical Benefit Rate (CBR=CR+PR+SD≥12 weeks). Secondary objectives include progression-free survival (PFS), toxicity, tolerability as well as pharmacokinetics (PK) and pharmacodynamics (PD). Patients are treated with gemcitabine at 800 mg/m2 day 1 and 8, and REOLYSIN administered IV at day 1, 2 and 8, 9. Tumor assessment is performed every 2 cycles (6 weeks). A two stage design is used for this study. In stage 1 at least 3/17 patients must achieve CBR in order to proceed to stage 2. Results: Fourteen patients were enrolled in the study and 10 are evaluable for efficacy. Age ranged from 48 to 82 years, mean 67 years. All patients except one reported symptomatic improvement. No CR were reported. Two patients have SD for ≥36 weeks and one patient continues on study with SD at 39 weeks. An additional patient had an unconfirmed PR of less than 6 weeks. Six patients had SD ≥ 12 weeks. The treatment was well tolerated with common non-hematological toxicities including grade 1 fever, chills, nausea and vomiting. Only two patients had grade 3 neutropenia lasting 1–2 days. No other grade 3 toxicities were seen. Conclusion: The endpoint for the first stage of the study (≥3 CBR in the first 17 patients) has been reached and therefore enrollment will continue. REOLYSIN in combination with gemcitabine has demonstrated clinical benefit in patients with unresectable Pca with a tolerable toxicity profile. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B55.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| 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 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".