Abstract CT142: A phase I open-label, dose escalation study of a novel peptide (SOR-C13) antagonistic to the TRPV6 ion channel in patients with advanced solid tumor cancers
Bibliographic record
Abstract
Abstract Background: SOR-C13 is a first-in-man selective peptide inhibitor of Transient Receptor Potential Vanilloid 6 (TRPV6) calcium oncochannel. TRPV6 is highly expressed in carcinomas including prostate, breast, lung and ovary and expression 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 late-stage carcinoma. 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 two 21-day cycles of treatment consisting of SOR-C13 for 3 d on/4 d off, 3 d on/11 d off (21 d/cycle). Tested doses were 1.375, 2.75, 4.13 and 6.2 mg/kg given as i.v. infusion initially over 20 m moving to 90 m. In the event of clinically meaningful response (tumor response or stable disease), additional cycles were offered to subjects. Subjects were assessed for safety, tolerability and preliminary efficacy. Results: Twenty-three subjects with advanced refractory solid tumors were in the study. No study drug-related serious adverse events occurred during the study. The most frequently reported treatment-emergent adverse events (TEAEs) were fatigue (30%), hypoalbuminemia (30%), anemia (30%), urinary tract infection (30%), blood calcium decreased (22%), decreased appetite (22%), nausea (22%), constipation (17%), aspartate aminotransferase increased (17%), cough (17%), blood alkaline phosphatase increased (13%), diarrhea (13%), hypercalcemia (13%), hyperkalemia (13%), hypocalcemia (13%). Anemia (Grade 1 to 3) was the only TEAE reflecting clinically significant hematological abnormalities. In all but one case, these events were assessed as unrelated or unlikely related to the study drug. The only safety concern identified definitely related to SOR-C13 infusion was reductions of serum calcium that were short-lived (resolved during the post-infusion observation time (4 h or within <24 h) and asymptomatic at all doses. A range of safe dosing was established between 4.13 and 6.2 mg/kg. Anti-tumor activity was observed across a wide variety of tumor types. Twelve of 22 evaluable subjects (54.5%) had stable disease after 2 cycles. The duration of response ranged from 4 to 7.5 cycles with one subject still in stable disease after 16 cycles (11 months). Two patients with advanced pancreatic cancer showed tumor reduction of 7% (4.13 mg/kg) and 27% (6.2 mg/kg) after two cycles with attendant decreases in CA 19-9. Conclusions: SOR-C13 was safe and well tolerated in subjects with advanced solid tumors of epithelial origin and demonstrates potential activity in patients with advanced solid tumor cancer. Citation Format: Siqing Fu, Hal H. Hirte, Stephen Welch, Toney T. Ilenchuk, Dominique Dugourd, Tyler Lutes, Christopher Rice, Jack M. Stewart. A phase I open-label, dose escalation study of a novel peptide (SOR-C13) antagonistic to the TRPV6 ion channel in patients with advanced solid tumor cancers. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT142.
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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 | 0.000 | 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 | 0.002 |
| 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".