Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Zilovertamab vedotin · 9 trials · 20 indications
PFS is defined as the time from randomization to the first documented disease progression per Lugano response criteria by blinded independent central review (BICR) or death due to any cause, whichever occurs first.
CRR at EOT is defined as the percentage of participants who experience complete response (CR) per Lugano response criteria as assessed by blinded independent central review (BICR) at end of treatment. CR is complete metabolic (no/minimal FDG uptake) and radiologic response (target lesions regress to ≤1.5 cm in longest transverse diameter of a lesion) and no new lesions. Participants with missing data or who discontinue treatment or study prior to reaching EOT will be considered non-responders and included in the total number of participants.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants with MCL (Cohort C), FL (Cohort D), and CLL (Cohort D) who experienced an AE will be reported.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants with MCL (Cohort C), FL (Cohort D), and CLL (Cohort D) who discontinued study treatment due to an AE will be reported.
The Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0 will be used to grade the severity of AEs. DLTs for participants with MCL (Cohort C) as assessed by investigator will be reported.
ORR, defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) per Lugano Response Criteria as assessed by BICR in Participants with MCL (Cohort A), RT (Cohort B), and FL (Cohort D) will be reported.
ORR, defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) per Lugano Response Criteria as assessed by investigator in Participants with MCL (Cohort C) will be reported.
ORR, defined as the percentage of participants who achieve a CR or PR per iwCLL criteria as assessed by investigator in participants with CLL (Cohort D) will be reported.
DLTs will be evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 and are defined as any drug-related adverse event (AE) observed during the DLT evaluation period (e.g. Cycle 1) that results in a change to a given dose or a delay in initiating the next cycle. The number of participants with DLTs in Cycle 1 will be reported.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experience an AE will be reported.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue study treatment due to an AE will be reported.
CRR is defined as the percentage of participants who achieve a Complete Response (CR) per Lugano response criteria \[Cheson, B. D., et al 2014\] for malignant lymphoma as assessed by the investigator. Assessment includes anatomic imaging with computed tomography (CT) or magnetic resonance imaging (MRI), metabolic imaging with positron emission tomography (PET), and clinical findings including physical examination and bone marrow biopsy results. The percentage of participants with CRR will be reported.
The CTCAE, Version 5.0 will be used to grade the severity of AEs in this study. DLTs will be reported for Part 1 of this study.
An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who experienced an AE will be reported.
OS, defined as the time from randomization to death due to any cause will be reported.
ORR is percentage of participants with complete response (CR) or partial response (PR). ORR by cohort, relapsed or refractory (rr) DLBCL as assessed by BICR according to Lugano Response Criteria 2014 in participants treated with zilovertamab vedotin Q3W. CR is the complete radiologic response. PR is a partial response, \>=50% decrease in sum of the product of the perpendicular diameters for multiple lesions for up to 6 target measurable nodes and extranodal sites.
Participants will receive zilovertamab vedotin according to Schedule 1, 2, or 3. The MTD will be determined by the number of participants who experience a dose limiting toxicity (DLT). The MTD will be defined as the highest tested dose level at which ≥6 participants have been treated and which is associated with a Cycle 1 DLT in ≤17% of the participants.
Selection of the RDR will be based on consideration of short- and long-term safety information together with available pharmacokinetic, pharmacodynamic, and efficacy data. The RDR may be the MTD or may be a lower dose within the tolerable dose range.
Number of participants experiencing toxicities that are possibly, probably, or definitely related to study therapy; that meet pre-defined severity criteria; and result in a change in the given dose.
An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product and does not imply any judgment about causality. The number of participants in Part 1 who experience at least 1 AE will be presented.
An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product and does not imply any judgment about causality. The number of participants in Part 1 who discontinue study treatment due to an AE will be presented.
An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product and does not imply any judgment about causality. The number of participants in Part 1 who receive a dose modification due to an AE will be presented.
OR for participants with B-ALL is defined as complete response (CR) or complete response with incomplete hematologic recovery (CRi) based on investigator's assessment per Ponte-di-Legno Consortium criteria. For Part 1 and Part 2, the OR for participants with B-ALL as assessed by investigator will be presented.
OR for participants with DLBCL/Burkitt lymphoma, neuroblastoma, and Ewing sarcoma is defined as complete response (CR) or partial response (PR) based on investigator's assessment per International Pediatric Non-Hodgkin Lymphoma (IPNHL) Response Criteria for participants with DLBCL/Burkitt lymphoma, per International Neuroblastoma Response Criteria (INRC) for neuroblastoma, and per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for Ewing sarcoma. For Part 1 and Part 2, the OR for participants with DLBCL/Burkitt lymphoma, neuroblastoma, and Ewing sarcoma as assessed by investigator will be presented.
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment
ORR is defined as the percentage of participants who achieve a Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.
ORR is defined as the percentage of participants who achieve a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience CR or PR as assessed by the investigator will be presented.
| Arm | Type | Description |
|---|---|---|
| Zilovertamab vedotin + Rituximab + Cyclophosphamide, Doxorubicin, Prednisone (R-CHP) | EXPERIMENTAL | Participants receive a dose of zilovertamab vedotin (1.75 mg/kg) plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 6 cycles (up to approximately 4 months) plus 2 cycles of rituximab or biosimilar for participants with high risk DLBCL. Participants also receive 100 mg prednisone, prednisolone, or methylprednisolone via oral tablet per day during Days 1-5 of each 21-day cycle for up to 6 cycles (up to approximately 4 months). |
| Rituximab + Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (R-CHOP) | ACTIVE_COMPARATOR | Participants receive 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar, 1.4 mg/m\^2 vincristine administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 6 cycles (up to approximately 4 months) plus 2 cycles of rituximab or biosimilar for participants with high risk DLBCL. Participants also receive 100 mg prednisone, prednisolone, or methylprednisolone via oral tablet per day during Days 1-5 of each 21-day cycle for up to 6 cycles (up to approximately 4 months). |
| Polatuzumab vedotin + R-CHP | ACTIVE_COMPARATOR | Participants will receive a dose of polatuzumab vedotin (1.8 mg/kg) plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar administered by IV infusion on Day 1 of each 3-week cycle for up to 6 cycles (up to approximately 4 months) plus 2 additional cycles of rituximab or biosimilar for participants with high risk DLBCL. Participants will also receive 100 mg prednisone or prednisolone via oral tablet per day during Days 1-5 of each 3-week cycle for up to 6 cycles (up to approximately 4 months). |
| Cohort A, Relapsed or Refractory MCL with 2 Prior Lines of Therapy | EXPERIMENTAL | Participants will receive zilovertamab vedotin intravenous (IV) infusion at Dose 1 every 3 weeks (Q3W) until disease progression or discontinuation. |
| Cohort B, Relapsed or Refractory RT with 1 Prior Line of Therapy | EXPERIMENTAL | Participants will receive zilovertamab vedotin IV infusion at Dose 1 every 3 weeks (Q3W) until disease progression or discontinuation. |
| Cohort C, Relapsed or Refractory MCL with 1 Prior Line of Therapy | EXPERIMENTAL | Participants will receive zilovertamab vedotin IV infusion at Dose 2 every 3 weeks (Q3W) combined with nemtabrutinib oral dose daily until disease progression or discontinuation. |
| Cohort D, Relapsed or Refractory FL and CLL with 2 Prior Lines of Therapy | EXPERIMENTAL | Participants will receive either zilovertamab vedotin IV infusion Dose 1 every 3 weeks (Q3W) until disease progression or discontinuation. |
| Zilovertamab Vedotin + R-CHP: Dose Escalation/Confirmation | EXPERIMENTAL | Participants in the dose escalation/confirmation phase receive a dose level of zilovertamab vedotin (from 1.5 mg/Kg up to 2.5 mg/Kg) plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar (truxima) administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 8 cycles (up to approximately 5.5 months). Participants also receive 100 mg prednisone or prednisolone per day during Days 1-5 of each 21-day cycle for up to 8 cycles (up to approximately 5.5 months). |
| Zilovertamab Vedotin + R-CHP: Efficacy Expansion | EXPERIMENTAL | Participants in the efficacy expansion phase receive the RP2D of zilovertamab vedotin plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar (truxima) administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 8 cycles (up to approximately 5.5 months). Participants also receive 100 mg prednisone or prednisolone per day during Days 1-5 of each 21-day cycle for up to 8 cycles (up to approximately 5.5 months). |
| ZV + R-GemOx (Part 1) | EXPERIMENTAL | Participants in this arm will receive doses of ZV (from 1.5 mg/Kg up to 2.5 mg/Kg) plus Rituximab 375 mg/m\^2, Gemcitabine 1000 mg/m\^2 and Oxaliplatin 100 mg/m\^2 (R-GemOx) given intravenously on Day 1 of repeated 21-day cycles. Treatment will continue for up to 6 cycles. |
| ZV + R-GemOx (Part 2) | EXPERIMENTAL | Using the recommended Phase 2 dose (RP2D) dose of ZV plus R-GemOx from Part 1, participants will receive ZV plus R-GemOx given intravenously on Day 1 of repeated 21-day cycles. Treatment will continue for up to 6 cycles or until progressive disease or discontinuation. |
| R-GemOx (active control for Part 2) | ACTIVE_COMPARATOR | Participants will receive R-GemOx given intravenously on Day 1 of repeated 21-day cycles. Treatment will continue for up to 6 cycles or until progressive disease or discontinuation. |
| ZV + BR (Part 2) | EXPERIMENTAL | Using RP2D from Part 1, participants will receive ZV plus Rituximab 375 mg/m\^2, given intravenously on Day 1 and Bendamustine 90 mg/m\^2 given intravenously on Day 1 and 2, of repeated 21-day cycles. Treatment will continue for up to 6 cycles or until progressive disease or discontinuation. |
| Bendamustine Rituximab (BR) | ACTIVE_COMPARATOR | Participants will receive Rituximab 375 mg/m\^2, given intravenously on Day 1 Bendamustine 90 mg/m\^2 given intravenously on Day 1 and 2 of repeated 21-day cycles. Treatment will continue for up to 6 cycles or until progressive disease or discontinuation. |
| ZV + BR (Part 1) | EXPERIMENTAL | Participants in this arm will receive doses of ZV (from 1.5 mg/Kg up to 2.5 mg/Kg) plus Rituximab 375 mg/m\^2, Bendamustine 90 mg/m\^2 (BR) given intravenously on Day 1 and 2 of repeated 21-day cycles. Treatment will continue for up to 6 cycles. |
| Arm A | EXPERIMENTAL | Participants will receive treatment with zilovertamab vedotin 2.5 mg/kg via intravenous (IV) infusion on Day 1 of each 21-day cycle (every 3 weeks (Q3W)) until documented disease progression or any other discontinuation criterion is met. |
| Arm B | EXPERIMENTAL | Participants will receive treatment with zilovertamab vedotin 2.25 mg/kg via intravenous (IV) infusion on Day 1 of each 21-day cycle (every 3 weeks (Q3W)) until documented disease progression or any other discontinuation criterion is met. |
| Zilovertamab vedotin Schedule 1: Q1/3W | EXPERIMENTAL | Participants will be administered escalating doses of zilovertamab vedotin at 0.50, 1.00, 1.50, 2.25, 2.50, 2.75, and 3.00 mg/kg IV on Day 1 of repeated 21-day cycles (Q1/3W). |
| Zilovertamab vedotin Schedule 2: Q2/3W | EXPERIMENTAL | Participants will be administered escalating doses of zilovertamab vedotin at 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, and 2.25 mg/kg IV on Day 1 and 8 of repeated 21-day cycles (Q2/3W). |
| Zilovertamab vedotin Schedule 3: Q3/4W | EXPERIMENTAL | Participants will be administered escalating doses of zilovertamab vedotin at 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, and 2.25 mg/kg IV on Day 1, 8, and 15 of repeated 21-day cycles (Q3/4W). |
| Zilovertamab vedotin | EXPERIMENTAL | Participants receive escalating doses of zilovertamab vedotin via intravenous (IV) infusion on Day 1 of each 21-day cycle (every 3 weeks). |
| Arm A: Zilovertamab vedotin | EXPERIMENTAL | Participants will receive zilovertamab vedotin 2mg/kg administered on Day 1 and Day 8 of each 3 week cycle (Q3W) until documented disease progression or any other discontinuation criterion is met. |
| Arm B: Pembrolizumab and MK-3120 | EXPERIMENTAL | Participants will receive MK-3120 up to 5mg/kg administered on Day 1, Day 15 and Day 29 of each 6 week cycle until documented disease progression or any other discontinuation criterion is met and 400mg pembrolizumab on Day 1 of each 6 week cycle for up to 17 cycles (up to \~2 years). |
| Name | Type | Description |
|---|---|---|
| Zilovertamab vedotin | BIOLOGICAL | IV infusion |
| Rituximab | BIOLOGICAL | IV infusion |
| Cyclophosphamide | DRUG | IV infusion |
| Doxorubicin | DRUG | IV infusion |
| Rituximab Biosimilar | BIOLOGICAL | IV infusion |
| Prednisone | DRUG | Per Approved Product Label |
| Prednisolone | DRUG | Oral administration |
| Vincristine | DRUG | IV infusion |
| Rescue medication | DRUG | Participants receive rescue medication per approved product label. The rescue medication is granulocyte colony-stimulating factor (G-CSF). |
| Methylprednisolone | DRUG | Per Approved Product Label |
| Polatuzumab vedotin | BIOLOGICAL | IV infusion |
| Nemtabrutinib | DRUG | Oral tablet |
| Gemcitabine | DRUG | IV Infusion 1000 mg/m\^2 |
| Oxaliplatin | DRUG | IV Infusion 100 mg/m\^2 |
| Bendamustine | DRUG | IV Infusion 90 mg/m\^2 |
| Granulocyte Colony-Stimulating Factor (G-CSF) | DRUG | Prophylactic G-CSF will be administered at each cycle of zilovertamab vedotin as per the institutional guidelines. |
| Pembrolizumab | BIOLOGICAL | Administered via IV infusion on Day 1 of each 6 week cycle. |
| MK-3120 | BIOLOGICAL | Administered as an IV infusion on Day 1, Day 15, and Day 29 of each 6 week cycle. |
Inclusion Criteria: * Has histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL), by prior biopsy, based on local testing according to the WHO classification of neoplasms of the hematopoietic and lymphoid tissues * Has positron emission tomography (PET) positive disease at scre...
Zilovertamab Vedotin is an investigational monoclonal antibody being studied for Diffuse Large B-Cell Lymphoma (DLBCL), including relapsed or refractory DLBCL, B-cell Acute Lymphoblastic Leukemia, and Chronic Lymphocytic Leukemia. It is being evaluated in combination with standard of care regimens for these B-cell malignancies.
Zilovertamab Vedotin is being developed by Merck & Company, Inc. (ticker: MRK). The company is conducting clinical trials to evaluate the drug in patients with relapsed or refractory Diffuse Large B-Cell Lymphoma and other B-cell malignancies.
Zilovertamab Vedotin is in Phase 2 clinical development. It is an investigational drug and has not been approved by regulatory authorities. Ongoing trials are evaluating its safety and efficacy in patients with Diffuse Large B-Cell Lymphoma.
Zilovertamab Vedotin is being studied in two Phase 2 trials: NCT05139017, a study of the drug in combination with standard of care in relapsed or refractory DLBCL, and NCT05144841, a completed study in relapsed or refractory DLBCL. Both trials enroll adults aged 18 years and older.
Zilovertamab Vedotin is a monoclonal antibody that targets a specific antigen on B-cells. It is designed to deliver a cytotoxic agent to cancer cells expressing this target, which is relevant in B-cell malignancies such as Diffuse Large B-Cell Lymphoma and Chronic Lymphocytic Leukemia.
Yes, Zilovertamab Vedotin is also known as MK-2140. Clinical trials such as NCT05139017 and NCT05144841 refer to the drug as MK-2140, and it is being developed by Merck & Company, Inc. for the treatment of B-cell lymphomas.