A Phase I/II Trial to Evaluate the Safety, Pharmacokinetics, and Efficacy of Glofitamab As Monotherapy and in Combination with R-ICE Chemoimmunotherapy in Children and Young Adults with Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma (iMATRIX-GLO)
Bibliographic record
Abstract
Background: Although rare,relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL) in children, adolescents, and young adults is an area of high unmet need, with 1-year overall survival rates of <30% and complete remission (CR) rates of 27% after treatment with R-ICE (rituximab, ifosfamide, carboplatin, and etoposide) chemoimmunotherapy (Burke et al. Leukemia 2020). New treatment regimens are urgently needed (Woessmann et al. Blood 2020; Burkhardt et al. Cancers (Basel) 2021). T-cell engagers have been identified as medicinal products with the greatest probability of being beneficial for the pediatric population (Pearson et al. Eur J Cancer 2019). Glofitamab is a CD20xCD3 T-cell engaging bispecific antibody that redirects T cells to eliminate B cells and is currently under investigation as monotherapy and in combination with chemoimmunotherapy for the treatment of adults with R/R B-NHL, with encouraging clinical activity and a manageable safety profile. Known risks associated with glofitamab are cytokine release syndrome (CRS), febrile neutropenia, tumor flare, tumor lysis syndrome, pyrexia, and infections. The safety profile of glofitamab in children is expected to be similar to that seen in adults. Study Design and Methods: iMATRIX-GLO (NCT05533775) is a Phase I/II, open-label, single-arm, two-part trial to evaluate the safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of glofitamab as monotherapy in children 6 months to <18 years of age with second and higher R/R B-NHL (i.e. relapse after 2 or more lines of treatment), or in combination with R-ICE in children and young adults ≤30 years of age with first R/R disease (i.e. relapse after the first line of treatment). Patients with a histologically confirmed diagnosis of CD20-positive R/R B-NHL are eligible. Study treatment is administered with a single dose of obinutuzumab pretreatment followed by glofitamab step doses and repeated glofitamab full doses every 21 days as monotherapy or in combination with R-ICE. Primary objectives and endpoints are the achievement of CR after up to three cycles of combination therapy (glofitamab plus R-ICE) as determined by the investigator according to the International Pediatric NHL Response Criteria for pediatric participants and Lugano Classification for young adult participants, evaluation of glofitamab safety (CRS by ASTCT 2019 criteria, otherwise by NCI CTCAE v5.0 criteria), tolerability, and PK as monotherapy and as combination therapy. The first patient was enrolled in November 2022 and the study is ongoing. The study is planned at 23 sites in 9 countries (Europe, Australia, North America, South Korea, and China).
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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 | 0.003 |
| Insufficient payload (model declined to judge) | 0.006 | 0.002 |
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".