Obinutuzumab
| Evidence Level: L5 | Predicted Indications: 3 |
Table of Contents
- Obinutuzumab
- Obinutuzumab: From Acute Lymphoblastic Leukemia and Richter Syndrome to Follicular Lymphoma
Obinutuzumab: From Acute Lymphoblastic Leukemia and Richter Syndrome to Follicular Lymphoma
Note on candidate selection: The two highest-scoring predictions (99.21% each) are molecular subtypes of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): pregerminal center CLL/SLL and IGHV-mutated CLL/SLL. No trials or publications were compiled for either, and they are nomenclature subtypes of a disease where obinutuzumab is already established. They are not distinct repurposing opportunities. This report therefore focuses on follicular lymphoma (99.18%), the highest-ranked prediction with substantial supporting evidence.
One-Sentence Summary
Obinutuzumab is an anti-CD20 antibody, associated in the source knowledge graph with acute lymphoblastic leukemia and Richter syndrome. The TxGNN model predicts it may be effective for follicular lymphoma, with more than 40 registered clinical trials and 19 publications, including several Phase 3 and Phase 2 randomized studies, supporting this direction. Follicular lymphoma is likely already an established obinutuzumab use, so this is better described as confirmation of a known use than as novel repurposing.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Acute lymphoblastic/lymphocytic leukemia; Richter syndrome (from the knowledge graph; no approved indication text was available for the US license) |
| Predicted New Indication | Follicular lymphoma |
| TxGNN Prediction Score | 99.18% |
| Evidence Level | L1 (rests mainly on the GALLIUM Phase 3 trial, reported in two publications, plus a Phase 3 trial discussed in a review; no individual completed Phase 3 trial is in the registered-trial list) |
| US Market Status | Cancelled only |
| Number of NDAs | 1 (BLA125486, cancelled) |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data is not available in the compiled data. Based on the literature, obinutuzumab is a glycoengineered, type II anti-CD20 monoclonal antibody. Compared with rituximab, it produces enhanced direct cell death and greater antibody-dependent cellular cytotoxicity and phagocytosis.
Follicular lymphoma is a CD20-positive B-cell malignancy, so the drug’s target matches the disease directly. The original leukemia-type indications are also B-lymphoid malignancies, which makes the prediction biologically coherent.
Phase 3 data (GALLIUM) support first-line use in follicular lymphoma. Phase 2 studies (GALEN, ROSEWOOD) support combinations in relapsed/refractory disease. The “Cancelled only” US market status should be verified, since it may reflect one product listing rather than the drug’s overall availability.
Clinical Trial Evidence
More than 40 trials were identified; the 10 most relevant are shown.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT05100862 | Phase 3 | Active, not recruiting | 799 | Zanubrutinib plus obinutuzumab vs lenalidomide plus rituximab in relapsed/refractory follicular or marginal zone lymphoma; primary endpoint is progression-free survival. Results not yet reported. |
| NCT05929222 | Phase 3 | Recruiting | 190 | Radiotherapy alone vs radiotherapy plus obinutuzumab in early-stage follicular lymphoma (GAZEBO). |
| NCT02871219 | Phase 2 | Completed | 96 | Obinutuzumab plus lenalidomide in previously untreated follicular lymphoma. |
| NCT03817853 | Phase 4 | Completed | 114 | Short-duration (about 90-minute) obinutuzumab infusion with chemotherapy in untreated advanced follicular lymphoma; evaluates administration safety only. |
| NCT05169658 | Phase 2 | Completed | 42 | Pilot of subcutaneous mosunetuzumab with or without polatuzumab vedotin and obinutuzumab in untreated indolent B-cell lymphoma. |
| NCT05387616 | Phase 2 | Unknown | 98 | Chemotherapy-free copanlisib plus obinutuzumab in untreated high-tumor-burden follicular lymphoma. |
| NCT00825149 | Phase 1 | Completed | 137 | Safety and efficacy of obinutuzumab combined with CHOP, FC or bendamustine in CD20+ follicular lymphoma. |
| NCT02257567 | Phase 1/2 | Completed | 331 | Polatuzumab vedotin plus bendamustine and rituximab or obinutuzumab in relapsed/refractory follicular or diffuse large B-cell lymphoma. |
| NCT01582776 | Phase 1/2 | Completed | 317 | Obinutuzumab plus lenalidomide in follicular and relapsed/refractory aggressive B-cell lymphoma. |
| NCT02391545 | Phase 1/2 | Terminated | 55 | Duvelisib with rituximab or obinutuzumab in untreated CD20+ follicular lymphoma; terminated early, limiting interpretation. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 28976863 | 2017 | Primary trial report (GALLIUM) | N Engl J Med | Compared rituximab-based with obinutuzumab-based chemotherapy in previously untreated advanced follicular lymphoma. |
| 29856692 | 2018 | RCT | J Clin Oncol | GALLIUM: obinutuzumab significantly prolonged progression-free survival vs rituximab across chemotherapy backbones (CHOP, CVP, bendamustine) in 1,202 patients. |
| 37404773 | 2023 | RCT | HemaSphere | GALLIUM final analysis in follicular and marginal zone lymphoma; the primary analysis met its endpoint of improved progression-free survival in follicular lymphoma. |
| 37506346 | 2023 | Randomized Phase 2 | J Clin Oncol | ROSEWOOD: zanubrutinib plus obinutuzumab vs obinutuzumab alone in relapsed/refractory follicular lymphoma. |
| 39376156 | 2024 | Patient-reported outcomes | Curr Med Res Opin | ROSEWOOD quality-of-life data; the trial showed superior efficacy and a manageable safety profile for the combination. |
| 31296423 | 2019 | Single-arm Phase 2 | Lancet Haematol | GALEN: obinutuzumab plus lenalidomide in previously treated relapsed/refractory follicular lymphoma. |
| 37767550 | 2024 | Phase 1b/2 cohort | Haematologica | Polatuzumab vedotin plus bendamustine and rituximab or obinutuzumab in relapsed/refractory follicular lymphoma. |
| 38041532 | 2024 | Meta-analysis | Cancer | Network meta-analysis of maintenance and consolidation strategies in untreated advanced follicular lymphoma. |
| 28324270 | 2017 | Review | Target Oncol | Reviews obinutuzumab in rituximab-refractory or -relapsed follicular lymphoma; in the Phase 3 GADOLIN study, obinutuzumab plus bendamustine followed by maintenance prolonged progression-free survival. |
| 31360086 | 2017 | Review | Blood Lymphat Cancer | Reviews obinutuzumab alone and in combination for follicular lymphoma. |
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| BLA125486 (cancelled) | Gazyva (Genentech, Inc.) | Injection, solution, concentrate | Not specified in the compiled data |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted immunotherapy (anti-CD20 monoclonal antibody), not a conventional cytotoxic agent |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Complete blood count with differential is generally advisable; please refer to the package insert for the full list |
| Handling Protection | Please refer to the package insert and institutional guidance for handling antineoplastic biologics |
Safety Considerations
- Drug Interactions: 81 interactions were identified.
- Major: deferiprone, samarium (153Sm) lexidronam, adalimumab, baricitinib, certolizumab pegol, cladribine, clozapine.
- Moderate: other immunosuppressive or biologic agents (e.g., alemtuzumab, azathioprine, anakinra, canakinumab), several vaccines including live and inactivated types, chloramphenicol, zidovudine, roflumilast and strontium chloride Sr-89.
- Most of these likely reflect additive immunosuppression or myelosuppression, and vaccine interactions need particular attention.
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Obinutuzumab’s anti-CD20 mechanism directly matches follicular lymphoma, and randomized evidence (GALLIUM, ROSEWOOD) plus a large trial pipeline support its use. Follicular lymphoma is probably an established indication, so the main work is confirming regulatory status rather than proving efficacy. The two top-ranked CLL/SLL subtype predictions have no subtype-specific evidence and should stay on Hold.
To proceed, the following is needed:
- Package insert warnings and contraindications (required before safety screening)
- Detailed mechanism-of-action data
- Verification of the “Cancelled only” US market status and the approved indication text for BLA125486
- A review of the major interaction pairs, especially with other immunosuppressants and vaccines, for the intended patient population
- Confirmation that the Phase 3 evidence (GALLIUM, GADOLIN) is accepted for the intended population and setting
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.