Background: Relapsed/refractory (R/R) mature B-cell non-Hodgkin lymphoma (B-NHL) in children, adolescents, and young adults is very rare and remains an area of high unmet need. The current 1-year overall survival is <30% and the complete response (CR) rate following treatment with rituximab, ifosfamide, carboplatin and etoposide (R-ICE) chemoimmunotherapy is 19% (Burke, et al. Blood Adv 2023). New effective treatment regimens are needed. T-cell engagers have been prioritized for evaluation in pediatric populations (Pearson, et al. Eur J Cancer 2019). Glofitamab is a CD20xCD3 bispecific antibody that was recently approved as monotherapy for the treatment of adult patients with R/R diffuse large B-cell lymphoma after ≥2 lines of therapy; in these patients, glofitamab monotherapy induced high response rates with manageable safety (Dickinson, et al. N Engl J Med 2022).
iMATRIX-GLO (NCT05533775) is a prospective, Phase I/II, open-label, single-arm, two cohort trial evaluating the safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of glofitamab in combination with R-ICE (Glofit+R-ICE) in children and young adults (up to 30 years) with R/R B-NHL after one prior line of therapy (Cohort A) and as monotherapy in children (6 months to <18 years) with R/R B-NHL after ≥2 lines of prior therapy (Cohort B). Here, we report initial safety and efficacy data from the first six pediatric patients.
Methods: Eligible patients had CD20+ R/R B-NHL, measurable disease, and adequate organ function. Informed consent was obtained prior to enrollment. Obinutuzumab pretreatment was administered prior to glofitamab step-up dosing. Patients treated with Glofit+R-ICE received up to three 21-day treatment cycles and those treated with glofitamab monotherapy were eligible to receive up to 12 cycles. Primary endpoints included achievement of a CR after up to three cycles of combination therapy (according to the International Pediatric NHL Response Criteria for pediatric patients and the Lugano classification for young adult patients), evaluation of glofitamab safety (cytokine release syndrome [CRS] events were graded by ASTCT criteria, other adverse events [AEs] by NCI CTCAE v5.0) and tolerability for the combination arm, as well as glofitamab PK for both arms. The study is open in 20 sites across eight countries; the first patient was enrolled in November 2022.
Results: As of 8 April 2024,six children were enrolled in the study; median age was 15 years (range: 7-18). Five patients had Burkitt lymphoma and one had Burkitt leukemia. Three patients had R/R B-NHL and one prior line of therapy and received Glofit+R-ICE for up to three cycles. Three patients had R/R B-NHL and ≥2 prior lines of therapy and received glofitamab monotherapy for up to five cycles. All three patients who received Glofit+R-ICE achieved a CR, of whom two subsequently underwent hematopoietic stem cell transplantation (HSCT) and remained in remission up to 12 months post-transplant. One patient relapsed prior to reaching HSCT. All three patients who received glofitamab monotherapy had progressive disease.
Overall, safety was manageable and similar to that observed in adults. CRS was the most common AE, reported in all six patients. Low-grade CRS occurred in four patients (Grade [Gr] 1, n=3; Gr 2, n=1), with high-grade CRS occurring in two patients (Gr 3, n=1; Gr 4, n=1) who received glofitamab monotherapy. All CRS events resolved. Hematological toxicities were the second-most frequently reported AEs, and included anemia, neutropenia, and thrombocytopenia. No fatal AEs were reported. No AEs led to discontinuation of glofitamab therapy.
Conclusions: In this ongoing iMATRIX-GLO study, initial data showed encouraging efficacy for Glofit+R-ICE in three children with R/R B-NHL and one prior line of therapy, with all three patients achieving a CR. The overall safety of glofitamab in combination or as monotherapy was manageable and consistent with the safety profile observed in adults. Future data will further establish the safety and efficacy of glofitamab in pediatric patients with R/R B-NHL. Updated data will be presented.
Minard-Colin:F. Hoffmann-La Roche Ltd/Genentech, Inc., BMS, Novartis, Adaptimmune, Servier, Sanofi, Miltenyi: Speakers Bureau; F. Hoffmann-La Roche Ltd/Genentech, Inc., BMS, Novartis, Adaptimmune: Research Funding; Gustave Roussy: Current Employment. Andión Catalán:Honoraria from Roche as payment for the development of audiovisual resources to improve information for adolescent with cancer, in collaboration with the Spanish Pediatric Oncology Society. Economic support from Roche to assist to SEHOP congress: Honoraria. Vinti:Amgen, Takeda: Speakers Bureau; Merck Sharp & Dohme: Research Funding; Amgen, Clinigen: Consultancy; Amgen, Neovii, Takeda: Other: Travel, accommodations, expenses. Kang:Takeda: Other: Travel/Accommodations/Expenses; GPCR: Other: Research funding to my institution; Takeda, Handok Teva, Recordati, Novartis, MSD: Consultancy. Rahmani:Roche Products Ltd: Current Employment. Gamel:F. Hoffmann-La Roche Ltd Pharmaceuticals: Current Employment, Current equity holder in private company. Wulff:Genentech, Inc., a member of F. Hoffmann-La Roche Ltd: Current Employment; F. Hoffmann-La Roche Ltd: Current holder of stock options in a privately-held company. Chohan:F. Hoffmann-La Roche Ltd: Current Employment. Negricea:Roche: Current Employment, Current equity holder in publicly-traded company, Ended employment in the past 24 months. Wulff:F. Hoffmann-La Roche Ltd.: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties; aPODD Foundation, UK: Membership on an entity's Board of Directors or advisory committees. Burkhardt:Novartis: Membership on an entity's Board of Directors or advisory committees; Miltenyi, Roche, Novartis, Janssen, AbbVie: Consultancy; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Miltenyi: Consultancy.
Glofitamab (Columvi) is a bispecific CD20-directed CD3 T-cell engager indicated for the treatment of adult patients with relapsed or refractory DLBCL, NOS or large B-cell lymphoma arising from FL, after two or more lines of systemic therapy.
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