Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Cevostamab · 9 trials · 3 indications
Adverse events will be reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0). The severity of CRS, immune effector cell-associated neurotoxicity syndrome (ICANS) and hemophagocytic lymphohistiocytosis (HLH) will be graded based on the American Society for Transplantation and Cellular Therapy (ASTCT) Grading Scales.
Dose-Limiting Toxicities (DLTs) will be reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), except for Cytokine release syndrome (CRS), which will be graded according to the American Society of Transplantation and Cellular Therapy (ASTCT) Consensus Grading for Cytokine Release Syndrome.
Cytokine release syndrome was recorded as an AE that generally occurs \>30 minutes after the start of Cevostamab administration and at any time afterward in a given cycle.
| Arm | Type | Description |
|---|---|---|
| Cevostamab + Pomalidomide + Dexamethasone | EXPERIMENTAL | Cevostamab will be administered intravenously on a 21-day cycle in cycle 1 and on a 28-day cycle from cycle 2 onwards. Pomalidomide will be administered orally (PO) on a 28-day cycle from cycle 2 onwards. Dexamethasone will be administered as a premedication prior to cevostamab. |
| Standard of Care (SOC) | ACTIVE_COMPARATOR | Participants will receive investigator's choice of one SOC regimen. |
| Dose Escalation and Expansion | EXPERIMENTAL | The study consists of a dose-escalation stage followed by an expansion stage. Participants in both stages will receive Cevostamab in a step-up dosing regimen, followed by a target dose. |
| Cevostamab | EXPERIMENTAL | Participants will receive cevostamab administered by intravenous (IV) infusion in 21-day cycles. |
| Substudy 2: Dose Escalation and Expansion | EXPERIMENTAL | In the pre-phase, participants will receive 2 step-up doses and a target dose of cevostamab. The step-up dose will be given on Day(D)1 and D4. The target dose will be given on D8. Subsequently the target dose will be administered on D1 and D15 for cycles 1-6 and D1 of cycle 7 onwards. Each cycle is 28 days. Lenalidomide will be administered by mouth (PO) on a 28-day cycle. During the dose expansion phase, cevostamab will be administered following the same dosing schedule as the dose escalation phase. The target dose will be determined after the escalation phase. Lenalidomide will be administered PO on a 28-day cycle. Enrollment for Substudy 2 has closed. |
| Substudy 4: Dose Escalation and Expansion | EXPERIMENTAL | In the pre-phase, participants will receive 2 step-up doses and a target dose of cevostamab. The step-up dose will be given on D1 and D4. The target dose will be given on D8. Subsequently the target dose will be administered on D1 of each cycle, every 3 weeks (Q3W). Each cycle is 21 days. Iberdomide will be administered PO on a 21-day cycle. During the dose expansion phase, cevostamab will be administered following the same dosing schedule as the dose escalation phase. The target dose will be determined after the escalation phase. Iberdomide will be administered PO on a 21-day cycle. |
| Safety Lead-In Cohort | EXPERIMENTAL | Participants will receive cevostamab, intravenously (IV), in combination with elranatamab, subcutaneously (SC), with step-up dosing of each drug in pre-phase following which they will receive elranatamab, at the assigned dose as a SC injection until disease progression or unacceptable toxicity. Participants will also receive cevostamab at the assigned dose as IV infusion until disease progression or unacceptable toxicity or up to 1 year on treatment, whichever occurs first. |
| Dose Expansion Cohort (Combined Therapy) | EXPERIMENTAL | Participants will receive cevostamab, IV, in combination with elranatamab, SC, with step-up dosing in pre-phase following which they will receive elranatamab, at the assigned dose as a SC injection until disease progression or unacceptable toxicity. Participants will also receive cevostamab at the assigned dose as IV infusion until disease progression or unacceptable toxicity or up to 1 year on treatment, whichever occurs first. |
| Dose Expansion Cohort (Monotherapy) | EXPERIMENTAL | Participants will receive elranatamab SC, with step-up dosing in pre-phase following which they will receive elranatamab, at the assigned dose as a SC injection until disease progression or unacceptable toxicity. |
| Arm A: Dose-Escalation and Expansion: XmAb24306+Cevostamab | EXPERIMENTAL | Participants will receive escalating doses of XmAb24306 with a fixed dose regimen for cevostamab up to the maximum tolerated dose (MTD). After dose escalation has been completed, up to two expansion cohorts each investigating different XmAb24306 doses in combination with cevostamab may be enrolled. |
| Arm B: Single-Agent Cevostamab Expansion | EXPERIMENTAL | Participants will receive cevostamab alone. |
| Cohort A1: Prior BCMA antibody-drug conjugate (ADC) or chimeric antigen receptor T (CAR-T) | EXPERIMENTAL | Participants in Cohort A1 will be treated at the double step-up split dosing regimen. |
| Cohort A2: Prior BCMA Bispecific | EXPERIMENTAL | Participants enrolled into exploratory Cohort A2 will receive the same dosing regimen as Cohort A1. |
| Cohort B1: Prior BCMA CAR-T | EXPERIMENTAL | Participants enrolled in expansion Cohort B1, will be given cevostamab at the selected dosing regimen. |
| Cohort B2: Prior BCMA Bispecific | EXPERIMENTAL | Expansion Cohort B2 will be opened, after the initial results from Cohort A2, at the same dose as per Cohort B1. |
| Single-Agent Cevostamab (Arm A) | EXPERIMENTAL | Cohort A1S is a safety run-in arm evaluating cevostamab administered in 28-day cycles on a modified weekly schedule. Cohort A1E, an expansion cohort, has been opened and finished enrolling participants. Participants will be treated with single-agent cevostamab administered in 28-day cycles on a modified weekly schedule. |
| Cevostamab plus Pomalidomide and Dexamethasone (Pd) (Arm B) | EXPERIMENTAL | Participants will be treated with cevostamab monotherapy during a 14-day period prior to the start of pomalidomide treatment (cevostamab pre-phase). Cohort B1S is a safety run-in arm evaluating cevostamab and Pd administered in 28-day cycles every 2 weeks (Q2W) followed by every 4 weeks (Q4W) schedule. Additional safety run-in cohort(s) with lower target dose levels of cevostamab may be opened prior to opening the expansion cohorts. Two target dose levels of target dose level 1 (DL1) and lower dose level -1 (DL-1) of cevostamab will be selected for randomization in expansion cohorts (Cohorts B1E and B3E). An additional non-randomized expansion cohort (Cohort B4E) will be included. Expansion cohorts will follow the same Q2W/Q4W dosing schedule as Cohort B1S. |
| Cevostamab plus Daratumumab and Dexamethasone (Dd) (Arm C) | EXPERIMENTAL | Cohort C1S is a safety run-in arm evaluating cevostamab and Dd administered in 21 day cycles from Cycle(C)1 - C8 every 3 weeks (Q3W) and 28-day cycles from C9 onwards Q4W. Additional safety run-in cohort(s) with lower target dose levels of cevostamab may be opened prior to opening the expansion cohorts. Two target dose levels of DL1 and DL-1 of cevostamab will be selected for randomization in expansion cohorts. Expansion cohorts will follow the same Q3W/Q4W dosing schedule as Cohort C1S. |
| Arm A: Single Step Dose Escalation for Cevostamab | EXPERIMENTAL | Study drug will be administered intravenously on a 21-day cycle. The step-up dose will be given on Cycle 1 Day 1 and the target dose will be given on C1D8. Subsequently the target dose will be administered on Day 1 of each 21-day cycle. |
| Arm B: Double Step Dose Escalation for Cevostamab | EXPERIMENTAL | In Cycle 1, participants will receive 2 step-up doses and a target dose. The step-up dose will be given on Cycle 1 Day 1 and C1D8. The target dose will be given on C1D15. Subsequently the target dose will be administered on Day 1 of each 21-day cycle. |
| Arm C: Single Step Dose Expansion for Cevostamab | EXPERIMENTAL | The single step dose expansion stage of the study may use the dosing and assessment schedule from the single dose escalation arm in Cycle 1, based on data from Arm A. |
| Arm D: Double Step Dose Expansion for Cevostamab | EXPERIMENTAL | The double step dose expansion stage of the study may use the dosing and assessment schedule from the double step dose escalation arm in Cycle 1, based on data from Arm B. |
| Arm E: Expansion Phase for Tocilizumab Pretreatment | EXPERIMENTAL | All participants will receive a single dose of tocilizumab intravenously. An additional dose of tocilizumab may be instituted as premedication for subsequent Cycle 1 dose(s) of cevostamab and Cycle 1 cevostamab doses for other treatment arms. |
| Arm F: Single Step Dose Expansion for Cevostamab | EXPERIMENTAL | The single step dose expansion stage of the study may use the dosing and assessment schedule from the single dose escalation arm in Cycle 1, based on data from Arm A. |
| Arm G: Double Step Dose Expansion for Cevostamab | EXPERIMENTAL | The double step dose expansion stage of the study may use the dosing and assessment schedule from the double step dose escalation arm in Cycle 1, based on data from Arm B. |
| Arm H: Triple Step Dose Escalation for Cevostamab | EXPERIMENTAL | In Cycle 1, participants will receive 3 step-up doses and a target dose. The doses will be given on Cycle 1 Days 1, 2-4, 8, and 9-11. Subsequently the target dose will be administered on Day 1 of each 21-day cycle. |
| Arm I: Triple Step Dose Expansion for Cevostamab | EXPERIMENTAL | The triple step dose expansion stage of the study may use the dosing and assessment schedule from the triple step dose escalation arm in Cycle 1, based on data from Arm H. |
| Arm J: Expansion Phase for Tocilizumab Pretreatment | EXPERIMENTAL | All participants will receive a single dose of tocilizumab intravenously. An additional dose of tocilizumab may be instituted as premedication for subsequent Cycle 1 dose(s) of cevostamab and Cycle 1 cevostamab doses for other treatment arms. |
| Arm K: Compressed Double Step Dose Expansion for Cevostamab | EXPERIMENTAL | In Cycle 1, participants will receive 2 step-up doses and a target dose. The doses will be given on Cycle 1 Days 1, 4, and 8. Subsequently the target dose will be administered on Day 1 of each 21-day cycle. |
| Name | Type | Description |
|---|---|---|
| Cevostamab | DRUG | Participants will receive cevostamab IV as per the schedule given in the protocol. |
| Pomalidomide | DRUG | Participants will receive pomalidomide tablet orally PO as per the schedule given in the protocol. |
| Dexamethasone | DRUG | Participants will receive dexamethasone tablet orally PO or IV as per the schedule given in the protocol. |
| Daratumumab | DRUG | Participants will receive daratumumab SC as per the schedule given in the protocol. |
| Elotuzumab | DRUG | Participants will receive elotuzumab IV as per the schedule given in the protocol. |
| Carfilzomib | DRUG | Participants will receive carfilzomib IV as per the schedule given in the protocol. |
| Tocilizumab | DRUG | Tocilizumab may be used as rescue medication for participants who experience a cytokine release syndrome (CRS) event. |
| Lenalidomide | DRUG | Lenalidomide will be administered PO on days 1-21 of a 28-day cycle. |
| Iberdomide | DRUG | Iberdomide will be administered PO on days 1-14 of a 21-day cycle. |
| Elranatamab | DRUG | Elranatamab solution for injection will be administered SC as specified in each treatment arm. |
| XmAb24306 | DRUG | XmAb24306 will be administered intravenously on a 28-day cycle, for up to one year of treatment depending on clinical response. |
Inclusion Criteria: * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 at screening and immediately prior to start of administration of study treatment. * Individuals with ECOG Performance Status of 2 solely due to local symptoms of myeloma (e.g., pain) are eligible * MM diagn...
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Cevostamab is an investigational bispecific antibody being studied for the treatment of relapsed or refractory multiple myeloma and systemic lupus erythematosus. It is currently in Phase 1 clinical development for these conditions.
Cevostamab is a bispecific antibody that targets B cell maturation antigen (BCMA) on myeloma cells and CD3 on T cells, bridging them to trigger T-cell mediated killing of tumor cells. This mechanism is being evaluated in clinical trials for multiple myeloma.
Cevostamab is being developed by Roche Holding AG, which trades on the OTC market under the ticker RHHBY. The company is conducting multiple Phase 1 trials to evaluate the drug's safety and efficacy.
Cevostamab is in Phase 1 clinical development. It is not yet approved by the FDA and remains investigational. There are 7 total trials, with 6 active and 1 completed, involving a total enrollment of 1321 participants.
Cevostamab is being studied in several Phase 1 trials, including NCT03275103 (completed, dose-escalation in R/R MM), NCT05535244 (in BCMA-exposed patients), NCT05646836 (in combination with XmAb24306), and NCT06934044 (in Chinese participants). All trials focus on relapsed or refractory multiple myeloma.
Cevostamab is also known by its code name RO7187797, though no other alternative names have been reported. It is a distinct investigational bispecific antibody being developed by Roche for multiple myeloma and lupus.