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Also known as IV Glofitamab
Glofitamab · 9 trials · 9 indications
according to the 2014 Lugano Response Criteria
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsen during a study are also considered as adverse events.
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsen during a study are also considered as adverse events.
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsen during a study are also considered as adverse events.
Severity of CRS was determined according to the American Society for Transplantation and Cell Therapy (ASTCT) Consensus Grading Criteria, in which Grade 1 as fever (≥38.0°C) with or without other symptoms; Grade 2 as fever with hypotension not requiring vasopressors and/or hypoxia requiring the use of oxygen (low-flow); and Grade 3 as fever with hypotension requiring one vasopressor with or without vasopressin and/or hypoxia requiring the use of oxygen (high-flow).
| Arm | Type | Description |
|---|---|---|
| Glofitamab + Pola-R-CHP | EXPERIMENTAL | Participants will receive glofitamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP). |
| Pola-R-CHP | ACTIVE_COMPARATOR | Participants will receive Pola-R-CHP. |
| Obinutuzumab, Glofitamab and Polatuzumab | EXPERIMENTAL | All patients will receive 2 cycles of glofitamab and polatuzumab followed by an interim PET scan (iPET2). If iPET2 is negative (Deauville score 1-3), patients will receive 4 cycles of glofitamab-polaRminiCHP. If iPET is positive (Deauville score 4,5) with partial response or stable disease, patients will receive 6 cycles of glofitamab-pola-R-miniCHP (polatuzumab will be omitted from last 2 cycles to keep total number of doses at 6 per standard of care) |
| Glofitamab + R-CHOP Immunochemotherapy | EXPERIMENTAL | Participants will receive step-up doses of glofitamab, starting on Day 8 of Cycle 3 (2.5 mg), Day 15 of Cycle 3 (10 mg), then 30 mg glofitamab will be given every three weeks (Q3W) onwards, on Day 8 of Cycles 4-6 and on Day 1 of Cycles 7-10. (cycle length = 21 days) Participants will receive rituximab, cyclophosphamide, doxorubicin, and vincristine Q3W on Day 1 of Cycles 1-6. Prednisone or prednisolone will be administered daily (QD) on Days 1-5 of Cycles 1-6. (cycle length = 21 days) |
| Gemcitabine + Glofitamab + Oxaliplatin | EXPERIMENTAL | Participants will receive a single dose of intravenous (IV) obinutuzumab pretreatment 7 days prior to the first dose of glofitamab, followed by up to 8 cycles of glofitamab + gemcitabine + oxaliplatin. This will be followed by up to 4 cycles of glofitamab monotherapy, for a total of up to 12 cycles of glofitamab (cycle length = 21 days). |
| R/R DLBCL | EXPERIMENTAL | Participants will receive up to 3 21-day cycles of glofitamab, rituximab, ifosfamide, carboplatin, and etoposide (glofit-R-ICE). |
| Arm A: Glofit-GemOx | EXPERIMENTAL | Participants will receive up to 8 cycles of Glofit-GemOx (glofitamab in combination with gemcitabine and oxaliplatin) administered in 21-day cycles, followed by up to 4 cycles of glofitamab monotherapy. A single dose of obinutuzumab will be administered 7 days prior to the first dose of glofitamab. |
| Arm B: Mosun-GemOx | EXPERIMENTAL | Participants will receive up to 8 cycles of Mosun-GemOx (mosunetuzumab in combination with gemcitabine and oxaliplatin) administered in 21-day cycles. |
| Atezolizumab | EXPERIMENTAL | Participants will receive Glofitamab in combination with Atezolizumab up to the maximum tolerated dose (MTD). |
| Polatuzumab Vedotin | EXPERIMENTAL | Participants will receive Glofitamab in combination with polatuzumab vedotin up to the MTD. |
| Imaging Sub-study | EXPERIMENTAL | Participants will undergo positive-emission tomography/computed tomography (PET/CT) at screening, followed by an "Imaging Cycle," to replace Cycle 1 of the main study. Eligible participants will have the option roll-over to the atezolizumab arm of the main study from Cycle 2 onwards. |
| Part 1: Dose Escalation r/r NHL | EXPERIMENTAL | Dose finding in participants with r/r NHL: the study will explore different doses of glofitamab in the induction period, starting at a dose of 70 mcg administered in combination with standard of care doses of G/R CHOP and R-CHOP every 3 weeks (Q3W). Participants with r/r NHL will receive 6 cycles of induction treatment (G/R-CHOP). Glofitamab will be administered using step-up dosing for Cycle 2 on Days 8 and 15, followed by single doses on Day 8 for Cycles 3-6. Participants who achieve a complete response (CR), partial response (PR), or stable disease (SD) at the end of induction (EOInd) may optionally receive post-induction treatment (referred to as maintenance) with glofitamab alone. The use of G versus R in Cycle 1 will be compared in parallel dose escalation cohorts. |
| Part 2: DLBCL G/R-CHOP | EXPERIMENTAL | Participants with untreated DLBCL will receive G-CHOP or R-CHOP in Cycle 1, followed by G/R-CHOP + glofitamab for subsequent cycles. Glofitamab will be administered using step-up dosing for Cycle 2 on Days 8 and 15, followed by single doses on Day 8 for Cycles 3-6 (up to 8). The starting dose of glofitamab for each arm may be one or more levels below the MTD/OBD determined in Part I. |
| Part 2: DLBCL Pola-R-CHP | EXPERIMENTAL | Participants with untreated DLBCL will receive Pola-R-CHP + glofitamab on Day 1 of each 21-day cycle for a maximum of 6 cycles. Glofitamab will be administered using step-up dosing for Cycle 2 on Days 8 and 15, followed by single doses on Day 8 for Cycles 3-6. The starting dose of glofitamab for each arm may be one or more levels below the MTD/OBD determined in Part I. |
| Part I: Dose Escalation | EXPERIMENTAL | Participants (single participant cohorts) will receive obinutuzumab pretreatment (Gpt) 1000 milligrams (mg) single dose IV infusion on Day -7 followed by glofitamab IV infusion on Day 1 and Day 8 of Cycle 1. From Cycle 2 onwards, ascending doses of glofitamab will be administered on Day 1 of every 2 week (Q2W) cycle up to Cycle 12 (24 weeks) or until unacceptable toxicity or disease progression. Glofitamab dosing will be initiated at 5 micrograms (mcg) (flat dose) followed by doses of 15 mcg, 45 mcg, 135 mcg, 405 mcg and 810 mcg. |
| Part II: Dose Escalation | EXPERIMENTAL | In each treatment regimen, participants will receive Gpt 1000 mg IV infusion on Day -7; or 2000 mg either administered on Day -7, or split into two 1000 mg doses on Days -1 and -7. The first glofitamab IV infusion will be given on Day 1 of Cycle 1 and a total of 12 cycles will be administered. Monotherapy, glofitamab as a single agent: ascending doses of glofitamab administered on Day 1 of Q2W or every 3 week (Q3W) cycle until either the MTD/OBD is defined. Combination Therapy: From Cycle 2 onwards, a fixed dose of 1000 mg obinutuzumab will be administered via IV infusion in combination with ascending doses of glofitamab on Day 1 of Q3W cycle until either the MTD/OBD is defined. Step-up dosing: Q3W, participants will receive an initial low dose of glofitamab on Cycle 1 Day 1, followed by a higher dose on Cycle 1 Day 8; the total dose in Cycle 1 will not exceed the previously determined MTD. Higher doses may be explored from Cycle 2 or later cycles. |
| Part III: Dose Expansion | EXPERIMENTAL | Part III will start once MTD/OBD is defined. Participants will receive Gpt 1000 mg single dose IV infusion on Day -7, followed by glofitamab at a fixed dose regimen or step-up dose regimen on a Q2W or Q3W dosing schedule as determined in Part II. A total of 12 cycles will be administered. Combination Therapy: From Cycle 2 onwards, a fixed dose of 1000 mg obinutuzumab will be administered via IV infusion in combination with glofitamab at the dosing regimen determined in Part II. |
| Name | Type | Description |
|---|---|---|
| Glofitamab | DRUG | Participants will receive intravenous (IV) glofitamab |
| Polatuzumab vedotin | DRUG | Participants will receive IV polatuzumab vedotin in combination with R-CHP |
| Rituximab | DRUG | Participants will receive IV rituximab |
| Cyclophosphamide | DRUG | Participants will receive cyclophosphamide as part of CHP chemotherapy |
| Doxorubicin | DRUG | Participants will receive IV doxorubicin |
| Prednisone | DRUG | Participants will receive oral prednisone as part of CHP chemotherapy |
| Polatuzumab | DRUG | 1.8 mg/kg iv C1D1 onwards, every 3 weeks |
| Obinutuzumab: | DRUG | 1000 mg iv C1D1 (7 days prior to glofitamab administration) single dose |
| Tocilizumab | DRUG | Participants will receive tocilizumab as needed to manage cytokine release syndrome (CRS). |
| Vincristine | DRUG | Participants will receive 1.4 mg/m2 body surface area of vincristine IV as per schedule specified in the treatment arm. |
| Obinutuzumab | DRUG | Participants will receive IV obinutuzumab pretreatment |
| Gemcitabine | DRUG | Participants will receive IV gemcitabine for up to 8 cycles (cycle length = 21 days) |
| Oxaliplatin | DRUG | Participants will receive IV oxaliplatin for up to 8 cycles (cycle length = 21 days) |
| Ifosfamide | DRUG | Participants will receive IV ifosfamide for up to 3 cycles. |
| Carboplatin | DRUG | Participants will receive IV carboplatin for up to 3 cycles. |
| Etoposide | DRUG | Participants will receive IV etoposide for up to 3 cycles. |
| Mosunetuzumab | DRUG | Participants will receive IV mosunetuzumab in combination with gemcitabine and oxaliplatin for up to 8 cycles. |
| Atezolizumab | DRUG | Atezolizumab will be administered in combination with Glofitamab through IV infusion Q3W from Cycle 2, Day 1, for up to 16 cycles (Cycle = 21 days). |
| 89Zr-Df-IAB22M2C | DRUG | Participants will receive 89Zr-Df-IAB22M2C (Cycle 1 only) prior to obinutuzumab pre-treatment and again on Day 10 after dosing with glofitamab, followed by PET/CT. |
| Obinutuzumab (G) | DRUG | Obinutuzumab 1000 mg single dose IV infusion on Day 1 of Cycle 1 only |
| Rituximab (R) | DRUG | Rituximab will be administered as an IV infusion at a dose of 375 mg/m\^2 on Day 1 of each 21-day cycle starting from Cycle 1 to Cycle 6 (Part 1) or from Cycles 1-6 (up to 8) (Part 2: DLBCL R-CHOP). |
Inclusion Criteria: * Previously untreated participants with CD20-positive LBCL * Ability to provide tumor tissue * International prognostic index (IPI) score 2-5 * Eastern cooperative oncology group (ECOG) performance status of 0, 1, or 2 * At least one bi-dimensionally measurable lesion, defined ...
Glofitamab is an investigational bispecific antibody being studied for the treatment of B-cell lymphomas, including non-Hodgkin's lymphoma, diffuse large B-cell lymphoma (DLBCL), and Richter syndrome. It is being evaluated in combination with other agents such as rituximab, obinutuzumab, and polatuzumab vedotin in clinical trials.
Glofitamab is being developed by Roche Holding AG, which trades under the ticker RHHBY. The company is conducting clinical trials to evaluate the drug's safety and efficacy in patients with various B-cell malignancies.
Glofitamab is in Phase 1 and Phase 2 clinical trials. It is an investigational agent and has not been approved by regulatory authorities. Studies are ongoing to assess its safety and efficacy in treating B-cell lymphomas.
Glofitamab is being studied in several trials, including NCT03467373, a Phase 1 study in non-Hodgkin lymphoma and DLBCL; NCT03533283, a Phase 1b/II study in relapsed/refractory B-cell non-Hodgkin's lymphoma; NCT04313608, a Phase 1 study in DLBCL; and NCT06765317, a Phase 2 study in DLBCL.
Glofitamab is also known as IV Glofitamab, and it is studied in combination with obinutuzumab, referred to as Glofitamab + Obinutuzumab. These names refer to the same investigational drug, which is being evaluated alone or with other therapies.
Glofitamab is a bispecific antibody, a type of -mab (monoclonal antibody) therapy. It is designed to engage T-cells to target and destroy B-cells that express specific antigens, which is relevant in B-cell malignancies. Its mechanism involves bridging immune effector cells to tumor cells.