A phase I/II study of atezolizumab in pediatric and young adult patients with refractory/relapsed solid tumors (iMATRIX-Atezolizumab).
Bibliographic record
Abstract
10524 Background: Atezolizumab targets programmed death-ligand 1 (PD-L1), leading to enhanced anticancer T-cell response. The iMATRIX-Atezolizumab study (phase I/II, multicenter, open-label; NCT02541604) assessed the safety, pharmacokinetics (PK) and preliminary activity of atezolizumab in pediatric/young adult patients with refractory/relapsed solid tumors. Methods: Patients aged < 30 years with refractory/relapsed non-central nervous system solid tumors received atezolizumab every 3 weeks until loss of clinical benefit ( < 18 years old, 15mg/kg [maximum dose 1200mg]; ≥18 years old, 1200mg). Safety/PK were assessed across tumor types and initial response was assessed by tumor-type cohorts after approximately 10 patients in each cohort had been treated. Results: As of July 19 2016, 74 patients (median age 14 years; range 2–29) were enrolled: osteosarcoma, n = 12; Ewing sarcoma, n = 11; neuroblastoma, n = 11; rhabdomyosarcoma (RMS), n = 10; non-RMS soft tissue sarcoma, n = 10; Wilms tumor, n = 6; Hodgkin lymphoma (HL), n = 5; non-HL, n = 1; other tumor types, n = 8. PK data (n = 48) were similar to that in adults (geometric mean Cmin, µg/mL [cycle 2, day 1, pre-dose]: 53.6 [2– < 6 years old]; 54.1 [6– < 12 years old]; 62.0 [12– < 18 years old]; 68.0 [adult]). Most tumors, except HL, had < 1% (score 0) tumor cell [TC]/tumor-infiltrating immune cell (IC) PD-L1 expression with overall TC/IC-positive expression rates (≥1%, score 1–3) of 7% and 10%, respectively. All available HL samples had ≥5% (score 2–3) TC/IC PD-L1 expression. 67/71 patients who received atezolizumab (median cycles 2; range 1–10) had ≥1 adverse event (AE; mainly immune-related grade 1–2); 17 patients (24%) had treatment-related grade 3–4 AEs. One AE (grade 3 transaminase increase) led to study drug discontinuation. Common AEs were pyrexia (37%), fatigue (34%) and constipation (32%). 2/5 patients with HL had a partial response (PR); the only patient with atypical rhabdoid tumor (RT) had an unconfirmed PR. Conclusions: The PK and safety profile of atezolizumab in pediatric and young adult patients is similar to that in adults. Preliminary antitumor activity was seen in HL and RT; new cohorts are planned in RT and atypical teratoid RT. Clinical trial information: NCT02541604.
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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 | 0.000 |
| Open science | 0.000 | 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".