Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication LUNSUMIO is a bispecific CD20-directed CD3 T-cell engager indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). FDA label
Also known as SC Mosunetuzumab, Mosunetuzumab (IV), Mosunetuzumab (Cohorts A-C), Mosunetuzumab Intravenous (IV), ML44933, Lunsumio, Mosunetuzumab-axgb, BTCT 4465A
Mosunetuzumab · 15 trials · 19 indications
ORR was defined as the percentage of participants with complete response (CR)/partial response (PR), per IRF, per Lugano Response Criteria. Percentages have been rounded off.
PFS was defined as the time from randomization to first occurrence of disease progression (PD) or death from any cause, whichever occurred first, per IRF, per Lugano Response Criteria.
Drug-Free Remission is defined as achieving both of the following: Absence of disease activity maintained for 6 months after completion of mosunetuzumab treatment, and; not receiving any SLE-directed therapy (except for antimalarials) during the 6 months. Doses of prednisone (or equivalent) ≤5 mg/day to treat secondary adrenal insufficiency are permitted.
The number of participants with best overall response of complete response (CR) to protocol therapy will be reported. Response will be assessed using Cheson 2014 criteria if disease is not FDG-avid in initial screening, and by revised Lugano 2014 criteria if screening Fluorodeoxyglucose (FDG) positron emission tomography (PET) computed tomography (CT) (FDG PET/CT) demonstrated FDG-avid disease.
Complete response will be assessed using Cheson 2014 or Lugano criteria, utilizing simple 5 point score (Deauville score). For this study complete response will be a score of 1 (no uptake), 2 (uptake ≤ mediastinum), or 3 (uptake \>mediastinum but ≤ liver, with no new lesions, and no FDG-uptake in the bone marrow, that is not expected (i.e. due to growth factors or therapy
Using a modified 3+3 design in previously untreated c-Myc rearranged aggressive B cell lymphomas during the safety run-in period (cycle 1-2). Incidence of DLTs will be tabulated by dose level. All DLTs will be coded by system organ class, MedDRA preferred term, and severity grade using Common Terminology Criteria for Adverse Events (CTCAE )(version \[v\] 5.0). Cytokine Release Syndrome/Immune Effector Cell-Associated Neurotoxicity Syndrome (CRS/ICANS) toxicities will be reporting using with the American Society for Transplantation and Cellular Therapy (ASTCT) grading system. Safe dose of mosunetuzumab (or dose adjusted \[DA\] etoposide, doxorubicin, vincristine, cyclophosphamide, and prednisone \[EOPCH\]) will be specified.
Will be reported with exact 95% confidence interval.
Treatment-emergent adverse events (TEAE) are defined as adverse events possibly, probably, or definitely related to mosunetuzumab that occur on or after first dose of study treatment.
Treatment-emergent adverse events (TEAE) are defined as adverse events possibly, probably, or definitely related to mosunetuzumab that occur on or after first dose of study treatment.
Patients are consented and enrolled prior to autoSCT, and given the long delay from consent to treatment, this will allow evaluation of feasibility of this approach.
The CR rate was defined as the percentage of participants with CR. Assessments were made according to the Lugano 2014 Response Criteria.
| Arm | Type | Description |
|---|---|---|
| M+P (Arm A) | EXPERIMENTAL | Participants will receive subcutaneous (SC) mosunetuzumab plus intravenous (IV) polatuzumab vedotin (M+P). Mosunetuzumab will be administered on Days 1, 8, and 15 of Cycle 1, and thereafter on Day 1 of Cycles 2-8. Polatuzumab vedotin will be administered on Day 1 of each cycle up to Cycle 6. Cycle length = 21 days. |
| R-GemOx (Arm B) | ACTIVE_COMPARATOR | Participants will receive IV rituximab, IV gemcitabine, and IV oxaliplatin (R-GemOx) on Day 1 of each cycle for 8 cycles. Cycle length = 14 days. |
| M + Len (Arm A) | EXPERIMENTAL | Participants will receive mosunetuzumab for 12 cycles, plus lenalidomide from cycles 2-12 (Cycle length = 21 days for Cycle 1; cycle length = 28 days for Cycles 2-12) |
| R + Len (Arm B) | EXPERIMENTAL | Participants will receive weekly rituximab in Cycle 1, then on Day 1 of Cycles 3, 5, 7, 9, and 11. Participants will also receive lenalidomide in Cycles 1-12. (Cycle length = 28 days for Cycles 1-12) |
| M + Len (US Extension Arm C) | EXPERIMENTAL | Participants will receive mosunetuzumab for 12 cycles, plus lenalidomide from cycles 2-12 (Cycle length = 21 days for Cycle 1; cycle length = 28 days for Cycles 2-12) |
| Mosunetuzumab | EXPERIMENTAL | Participants will receive mosunetuzumab by subcutaneous (SC) injection. |
| Mosunetuzumab Treatment Group | EXPERIMENTAL | Participants in this group will receive Mosunetuzumab for eight (8) 21-day cycles. Total participation is about 3.5 years. |
| Cohort A | EXPERIMENTAL | Participants with high tumor burden with untreated follicular lymphoma (FL) will receive SC mosunetuzumab monotherapy for up to 17 cycles or until radiographic disease progression, study discontinuation, or death, whichever occurs first. Participants that achieve complete or partial metabolic response will have the option of receiving maintenance therapy with mosunetuzumab every 8 weeks for 1 year. |
| Cohort B | EXPERIMENTAL | Elderly participants with untreated diffuse large B-cell lymphoma (DLBCL) will receive SC mosunetuzumab monotherapy for up to 17 cycles or until radiographic disease progression, study discontinuation, or death, whichever occurs first. |
| Cohort C | EXPERIMENTAL | Participants with untreated marginal zone lymphoma (MZL) will receive SC mosunetuzumab monotherapy for up to 17 cycles or until radiographic disease progression, study discontinuation, or death, whichever occurs first. |
| Cohort D | EXPERIMENTAL | Participants with relapsed or refractory (R/R) mantle cell lymphoma (MCL) will receive SC mosunetuzumab monotherapy for up to 34 cycles or until radiographic disease progression, study discontinuation, or death, whichever occurs first. |
| Cohort E | EXPERIMENTAL | Participants with R/R Richter's transformation (RT), or R/R transformed follicular lymphoma (tFL) will receive SC mosunetuzumab monotherapy for up to 34 cycles or until radiographic disease progression, study discontinuation, or death, whichever occurs first. |
| Cohort 1 | EXPERIMENTAL | Participants receive mosunetuzumab 60 mg for cycles 1 and 2 (although fractionated for cycle 1), and 30 mg for all subsequent cycles after standard-of-care therapy with CD19-directed CAR T-cells |
| Cohort 2 | EXPERIMENTAL | Participants receive obinutuzumab (1000 mg for each subject) and glofitamab after standard-of-care therapy with CD19-directed CAR T-cells. The dose of glofitamab for each subject will be 30 mg, other than for cycle 1, which will be 12.5 mg glofitamab fractionated over two weeks. |
| Treatment (Mosunetuzumab and EPOCH) | EXPERIMENTAL | Patients receive mosunetuzumab IV, over 2-4 hours, on day 1, 8 and 15 of cycle 1 and day 1 of subsequent cycles. Patients receive etoposide IV, doxorubicin IV, and vincristine IV on days 1-4, cyclophosphamide IV, over 2 hours, on day 5 and prednisone PO BID on days 1-5 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity for up to 6 cycles. Patients undergo bone marrow aspiration and biopsy, tumor biopsy and may undergo echocardiography or MUGA at screening and PET scan, CT scan or MRI and blood sample collection throughout the study. |
| Consolidation Mosunetuzumab | EXPERIMENTAL | Mosunetuzumab will be given in a step-up dosing schedule beginning on Day 49 after autoSCT on C1D1, C1D8, C1D15, and then Day 1 of all cycles thereafter (each cycle is 21 days). Patients will undergo PET-CT restaging on Day 100 after autoSCT. Those in complete response (CR) will continue mosunetuzumab from Cycle 3 Day 1 through Cycle 8 Day 1 administered at 30 mg IV. Patients not in CR at Day 100 PET-CT will discontinue study treatment. |
| Arm 1 | EXPERIMENTAL | Participants will receive subcutaneous (SC) mosunetuzumab + CC-220 (dose escalation only) or SC mosunetuzumab + CC-99282. |
| Arm 2 | EXPERIMENTAL | Participants will receive intravenous (IV) glofitamab + CC-99282. |
| Arm A | EXPERIMENTAL | Participants with R/R CLL/SLL after two prior lines of therapy and who have had prior exposure to BTKi and/or venetoclax will receive mosunetuzumab subcutaneous (SC) monotherapy |
| Arm B | EXPERIMENTAL | Participants with R/R CLL/SLL after two or more prior lines of therapy, who are currently progressing on BTKi therapy, and who require salvage therapy as assessed by their treating physician will receive mosunetuzumab SC with BTKi overlap therapy for up to the first three cycles of mosunetuzumab SC. NOTE: Arm B is closed to enrollment. |
| Arm C (non-US participants only) | EXPERIMENTAL | Participants with R/R CLL/SLL after two or more prior lines of therapy and who have had prior exposure to BTKi and/or venetoclax will receive mosunetuzumab SC with venetoclax during dose escalation phase. Participants with R/R CLL/SLL after at least one prior line of therapy must have prior exposure to BTKi and/or venetoclax and \>12 months since last venetoclax exposure will receive mosunetuzumab SC with venetoclax during the dose expansion phase. During the dose expansion phase, a control cohort receiving the standard-of-care regimen of rituximab plus venetoclax has been added (this arm is open only to participants outside of the US). |
| Non-fractionated/Dose-finding | EXPERIMENTAL | Participants will receive a single dose of mosunetuzumab. |
| Fractionated/Dose-escalation | EXPERIMENTAL | Participants will receive a fractionated (divided) dose of mosunetuzumab on Days 1 and 8. |
| Intravenous (IV) Mosunetuzumab + Lenalidomide (Non-randomized) | EXPERIMENTAL | Participants will receive treatment with IV mosunetuzumab plus lenalidomide for 12 cycles total (cycle length = 21 days for Cycle 1, 28 days from Cycle 2 onward) |
| Subcutaneous (SC) Mosunetuzumab + Lenalidomide (Non-randomized) | EXPERIMENTAL | Participants will receive treatment with SC mosunetuzumab plus lenalidomide for 12 cycles total (cycle length = 21 days for Cycle 1, 28 days from Cycle 2 onward). Participants that have received complete metabolic response (CMR) or partial metabolic response (PMR) after 12 cycles of induction therapy with mosunetuzumab + lenalidomide will receive maintenance therapy with SC mosunetuzumab every 8 weeks (Q8W) for an additional 9 cycles. |
| Arm A: IV Mosunetuzumab + Len (Randomized) | EXPERIMENTAL | Participants will receive treatment with IV mosunetuzumab plus lenalidomide for 12 cycles total (cycle length = 21 days for Cycle 1, 28 days from Cycle 2 onward) |
| Arm B: SC Mosunetuzumab + Len (Randomized) | EXPERIMENTAL | Participants will receive treatment with SC mosunetuzumab plus lenalidomide for 12 cycles total (cycle length = 21 days for Cycle 1, 28 days from Cycle 2 onward) |
| Consolidation Therapy (Cohort A) | EXPERIMENTAL | Participants with a partial response to first-line chemotherapy will receive mosunetuzumab up to the recommended consolidation dose (RCD). |
| Elderly/Unfit Previously Untreated Monotherapy (Cohort B) | EXPERIMENTAL | Elderly/unfit participants with previously untreated DLBCL will receive mosunetuzumab at the previously determined recommended phase II dose (RP2D). |
| Elderly/Unfit Previously Untreated Combination Therapy (Cohort C) | EXPERIMENTAL | Elderly/unfit participants with previously untreated DLBCL will receive mosunetuzumab in combination with polatuzumab vedotin. |
| Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding | EXPERIMENTAL | Participants will receive M-CHOP up to the phase II recommended dose (RP2D). |
| Phase Ib: M-CHP-Pola Dose-Finding | EXPERIMENTAL | Participants will receive M-CHP-Pola up to the RP2D. |
| Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety Cohort | EXPERIMENTAL | Participants with 1L DLBCL will receive mosunetuzumab at the RP2D in combination with CHOP. |
| Phase II: M-CHP-Pola 1L DLBCL | EXPERIMENTAL | Participants with 1L DLBCL will receive M-CHP-Pola at a dose determined in the dose finding stage. |
| Phase II: Rituxumab (R)-CHP-Pola 1L DLBCL | ACTIVE_COMPARATOR | Participants with 1L DLBCL will receive R-CHP-Pola at a dose determined in the dose finding stage. |
| Phase II: M-CHOP 1L DLBCL | EXPERIMENTAL | Participants with 1L DLBCL will receive M-CHOP at a dose determined in the dose finding stage. NOTE: No participants were enrolled to this arm. |
| Dose Finding | EXPERIMENTAL | Participants will receive mosunetuzumab in combination with polatuzumab vedotin. Dose finding will be guided by the observed incidence of dose-limiting toxicities (DLTs) at each dose level. |
| Mosunetuzumab + Polatuzumab Vedotin 2L+ R/R FL | EXPERIMENTAL | Participants with at least one line of prior therapy (2L+) and that have relapsed or refractory (R/R) follicular lymphoma (FL) will receive mosunetuzumab + polatuzumab vedotin. |
| Mosunetuzumab + Polatuzumab Vedotin 2L+R/R DLBCL | EXPERIMENTAL | 2L+ participants with R/R diffuse large B-cell lymphoma will receive mosunetuzumab + polatuzumab vedotin. |
| Mosunetuzumab SC + Polatuzumab Vedotin 3L+R/R MCL | EXPERIMENTAL | Participants with at least 2 lines of prior therapy (3L+) will receive subcutaneous (SC) mosunetuzumab + polatuzumab vedotin. |
| Mosunetuzumab SC + Polatuzumab Vedotin 2L+R/R DLBCL | EXPERIMENTAL | 2L+ participants with R/R DLBCL will receive SC mosunetuzumab and polatuzumab vedotin. |
| Name | Type | Description |
|---|---|---|
| Mosunetuzumab | DRUG | Participants will receive SC mosunetuzumab on Days 1, 8, and 15 of Cycle 1, and on Day 1 of Cycles 2-8 (cycle length = 21 days). |
| Polatuzumab vedotin | DRUG | Participants will receive IV polatuzumab vedotin every three weeks (Q3W) for 6 cycles (cycle length = 21 days). |
| Tocilizumab | DRUG | Participants will receive IV tocilizumab as needed to manage cytokine release syndrome (CRS) events. |
| Rituximab | DRUG | Participants will receive IV rituximab on Day 1 of each cycle for 8 cycles (cycle length = 14 days). |
| Gemcitabine | DRUG | Participants will receive IV gemcitabine on Day 1 of each cycle for 8 cycles (cycle length = 14 days). |
| Oxaliplatin | DRUG | Participants will receive IV oxaliplatin on Day 1 of each cycle for 8 cycles (cycle length = 14 days). |
| Lenalidomide | DRUG | Participants will receive oral lenalidomide once daily on Days 1-21 of Cycles 2-12 (M + Len) or Cycles 1-12 (R + Len) |
| Tociluzumab | DRUG | Tocilizumab will be administered as needed to manage cytokine release syndrome (CRS) events |
| Mosunetuzumab (Cohorts A-C) | DRUG | Participants will receive SC mosunetuzumab for up to 17 cycles and for optional maintenance (Cohort A only) |
| Mosunetuzumab (Cohorts D-E) | DRUG | Participants will receive SC mosunetuzumab for up to 34 cycles |
| glofitamab | DRUG | 2.5 mg IV Cycle 1 Day 8; 10 mg IV Cycle 1 Day 15 then 30 mg every 21 days beginning Cycle 2 Day 1 through Cycle 12 |
| obinutuzumab | DRUG | 1000 mg IV on Cycle 1 Day 1. |
| Biopsy | PROCEDURE | Undergo tumor biopsy |
| Biospecimen Collection | PROCEDURE | Undergo blood sample collection |
| Bone Marrow Aspiration and Biopsy | PROCEDURE | Undergo bone marrow aspiration and biopsy |
| Computed Tomography | PROCEDURE | Undergo CT scan |
| Cyclophosphamide | DRUG | Given IV |
| Doxorubicin | DRUG | Given IV |
| Echocardiography | PROCEDURE | Undergo echocardiography |
| Etoposide | DRUG | Given IV |
| Magnetic Resonance Imaging | PROCEDURE | Undergo MRI |
| Multigated Acquisition Scan | PROCEDURE | Undergo MUGA |
| Positron Emission Tomography | PROCEDURE | Undergo PET scan |
| Prednisone | DRUG | Given PO |
| Vincristine | DRUG | Given IV |
| SC Mosunetuzumab | DRUG | Participants will receive SC mosunetuzumab for 12 cycles (cycle length = 21 days or 28 days for Cycle 1 and 28 days for Cycles 2-12) |
| IV Glofitamab | DRUG | Participants will receive IV glofitamab for 12 cycles (cycle length = 21 days) |
| Iberdomide | DRUG | Arm 1: Participants will receive oral CC-220 from Day 1-21 of Cycle 2-12 (cycle length = 28 days for Cycles 2-12) |
| Golcadomide | DRUG | Arm 1: Participants will receive oral golcadomide from Day 1-14 starting in either Cycle 1 or Cycle 2 through Cycle 12 (cycle length = 28 days for cycles when golcadomide is to be administered) Arm 2: Participants will receive oral golcadomide from Day 1-10 starting in either Cycle 1, Cycle 2 or Cycle 3 through Cycle 12 (cycle length = 21 days) |
| Venetoclax | DRUG | Participants will receive daily oral venetoclax. |
| Mosunetuzumab (IV) | DRUG | Participants will receive IV mosunetuzumab as defined by the study protocol |
| Mosunetuzumab (SC) | DRUG | Participants will receive SC mosunetuzumab as defined by the study protocol |
| Mosunetuzumab Intravenous (IV) | DRUG | Participants in cohorts A and B will receive IV mosunetuzumab. |
| Mosunetuzumab Subcutaneous (SC) | DRUG | Participants in Cohort C will receive SC mosunetuzumab. |
| Rituxumab | DRUG | Participants will receive rituxumab via IV. |
Inclusion Criteria: * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2 * CD20+ aggressive lymphoma as determined by the local hemopathology laboratory from the following diagnoses by 2016 World Health Organization classification of lymphoid neoplasms: DLBCL, not otherwise ...
Mosunetuzumab is an investigational monoclonal antibody developed by Roche Holding AG (ticker RHHBY). It is being studied in B-cell lymphomas, including follicular lymphoma, diffuse large B-cell lymphoma, extranodal marginal zone lymphoma, and B-cell non-Hodgkin lymphoma, as well as in chronic lymphocytic leukemia or small lymphocytic lymphoma and systemic lupus erythematosus.
Mosunetuzumab targets MS4A1 (CD20) together with the CD3 complex, specifically CD3E, CD3G, and CD3D. By binding these molecules, the antibody engages T cells through CD3 and B cells through CD20, directing T-cell activity toward B cells. It is classified as a binding agent and is given as an intravenous or subcutaneous monoclonal antibody.
Mosunetuzumab is developed by Roche Holding AG, which trades under the ticker RHHBY. Roche is the sponsor behind the clinical program studying the antibody across B-cell malignancies and, more recently, in systemic lupus erythematosus with or without active lupus nephritis.
Mosunetuzumab is investigational and remains in clinical development. Its trials span Phase 1 and Phase 2, including Phase 1 studies in diffuse large B-cell lymphoma and as consolidation therapy after autologous stem cell transplant in relapsed or refractory aggressive B-cell lymphoma, and Phase 2 studies in extranodal marginal zone lymphoma and systemic lupus erythematosus.
Mosunetuzumab is being studied in several trials, including NCT07598396 in systemic lupus erythematosus, NCT06569680 in newly diagnosed extranodal marginal zone lymphoma, NCT06249191 combined with chemotherapy in high grade B-cell lymphoma or diffuse large B-cell lymphoma, and NCT05412290 as consolidation therapy after autologous stem cell transplant in aggressive B-cell lymphoma.
Yes. SC Mosunetuzumab, Mosunetuzumab (IV), Mosunetuzumab (Cohorts A-C), and Mosunetuzumab Intravenous (IV) are alternative names for the same agent, Mosunetuzumab. The variations refer to subcutaneous and intravenous formulations and to study cohorts rather than to different drugs.