Initial safety assessment of MAGE-A10<sup>c796</sup>TCR T-cells in two clinical trials.
Bibliographic record
Abstract
3056 Background: MAGE-A10 is expressed in 10-50% of urothelial, melanoma, head and neck (HNC), and non-small cell lung cancers (NSCLC). Affinity-enhanced autologous MAGE-A10c796T cells directed towards MAGE-A10 tumor antigen in the context of HLA*02 (SPEAR T-cells) are being tested in 2 ongoing clinical trials (NCT02592577: NSCLC/NCT02989064: urothelial, melanoma, HNC). Methods: These first-in-human T-cell dose escalation studies utilize a modified 3+3 design to evaluate safety. Patients are enrolled after progression on at least one line of therapy. In the first treatment groups, lymphodepletion with Flu 30 mg/m2/day and Cy 600 mg/m2/day (NCT02989064) or Cy 600 mg/m2/day (NCT02592577) is administered on days -7 to -5. The initial dose is 0.1×109 transduced cells; additional dose levels are 1×109 and 5×109. Dose-limiting toxicities (DLT) are determined regardless of attribution to cell infusion and adjudicated by a Safety Review Committee. Cohort expansion will occur at the maximum tolerated dose. Results: 8 patients were treated with 0.1×109 MAGE-A10c796TCR T-cells (29Dec17). Adverse events (AEs) in ≥3 patients included anemia, thrombocytopenia, lymphopenia, leukopenia, neutropenia, vomiting, constipation, dyspnea and tachycardia. Grade (G) 3 AEs in ≥2 patients included thrombocytopenia, lymphopenia, leukopenia, neutropenia, anemia, pancytopenia, and hyponatremia; these were not reported as related to T-cell infusion. 1 event of cytokine release syndrome (CRS) and 1 increase in serum amylase were reported as related to T-cell infusion. SAEs included G5 disease progression, G4 CRS, G4 neutropenia, G4 thrombocytopenia, G4 sepsis, G4 abdominal pain, G4 supraglottic airway obstruction, G3 shortness of breath and G2 respiratory failure. There was 1 DLT of G4 CRS in a patient with NSCLC that resolved with tocilizumab and steroids. While no anti-tumor effects were observed at this dose, transduced cells were detectable in peripheral blood. Conclusions: MAGE-A10c796TCR T-cells at the 0.1×109 transduced cell dose show no evidence of on target or off target toxicity. 1 DLT of CRS was observed. The available data support continued investigation of MAGE-A10c796TCR T-cells at higher doses. Clinical trial information: NCT02592577; NCT02989064.
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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 | 0.004 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 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".