Abstract B83: Targeting TRPV6 oncochannel for the treatment of pancreatic cancer: A Phase I trial experience
Bibliographic record
Abstract
Abstract Background: SOR-C13 is a first-in-human selective peptide inhibitor of Transient Receptor Potential Vanilloid 6 (TRPV6) oncochannel. TRPV6 is highly elevated in carcinomas including prostate, breast, lung and ovary and is correlated with poor outcomes. TRPV6-mediated Ca2+ entry is responsible for maintaining a high proliferation rate, increasing cell survival and apoptosis resistance. Since SOR-C13 blocks TRPV6-mediated Ca2+ influx it was evaluated as a single agent in patients with metastatic carcinomas. Methods: This was a Phase I, multi-center, open-label, dose escalation study to assess safety and tolerability of SOR-C13 in subjects with advanced carcinomas commonly known to express the TRPV6 channel (NCT01578564). Subjects received intravenous infusion of SOR-C13 over 90 minutes for 3 d on/4 d off, 3 d on/11 d off (21 d/cycle) until tumor progression, prohibitive toxicity or patient withdrawal. Tumors were assessed according to RECIST 1.1. Results: A total of 23 patients were enrolled to 4 dose levels and 119 cycles of therapy were administered. No study drug-related SAEs occurred. Twelve of 22 evaluable subjects (54.5%) had stable disease after 2 cycles. Promising clinical benefit was observed in two patients with advanced metastatic ductal pancreatic cancer. Subject 304 showed stable disease (SD) at dose level of 2.75 mg/kg for 12 weeks, and was removed from the study for persistent grade 2 hepatic transaminase elevation for more than 21 days. Subject 312, treated at dose level of 6.2 mg/kg, showed 7% decrease in tumor size after 2 cycles and a 27% decrease after 4 cycles. Tumor marker CA 19-9 responses were consistent with most changes in tumor size over the treatment cycles with suggestions of a dose related response and correlation with tumor size. The response of this biomarker was particularly evident in the patient initially treated at 6.2 mg/kg where it decreased by 29% after cycle two and by 55% after cycle 4. This patient was removed from the study after a total of 27 weeks 2 days. Both subjects failed at least three prior regimens of anticancer therapy: Subject 304 (i) IMRT/Tomotherapy plus chemoradiation with Folfirinox, (ii) Carboplatin/gemcitabine/Tarceva (iii) Abraxane/Gemcitabine, (iv) IMRT/Tomotherapy; Subject 312 (i) Folfirinox; (ii) gemcitabine and Abraxane; and, (iii) Xeloda. Conclusions: SOR-C13 was safe and well tolerated in subjects with advanced epithelial malignancies. The clinical benefit observed in patients with metastatic pancreatic cancer, particularly 27% reduction of the sum of tumor diameters after 4 cycles warrants further investigation of this novel treatment in Phase II studies. Citation Format: Siqing Fu, Stephen Welch, Toney T. Ilenchuk, Dominique Dugourd, Tyler Lutes, Chris Rice, Jack M. Stewart.{Authors}. Targeting TRPV6 oncochannel for the treatment of pancreatic cancer: A Phase I trial experience. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr B83.
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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) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".