Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Brentuximab vedotin · 19 trials · 26 indications
OS is defined as the time from the date of randomization to date of death due to any cause
The time from the date of randomization to the date of first documentation of progressive disease (PD), death due to any cause, or receipt of subsequent anticancer chemotherapy to treat residual or progressive disease whichever occurred first.
Time from date of randomization to the first documentation of disease progression by independent review or to death due to any cause, whichever comes first
Confirmed ORR per RECIST v1.1 is defined as the proportion of participants whose best overall response is a confirmed complete response (CR) or partial response (PR) per RECIST v1.1.
Will be assessed per 2014 Lugano criteria and Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) criteria. Will be summarized with 95% confidence intervals.
Will be assessed by complete response + partial response per 2014 Lugano criteria and LYRIC criteria.
ORR was defined as the percentage of participants with complete response (CR) or partial response (PR) following the completion of study treatment (at end of treatment \[EOT\]). CR and PR per Cheson 2007: CR was defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy and PR was defined as at least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses.
Objective response rate (ORR) per investigator was defined as the percentage of subjects with complete response (CR) or partial response (PR) through the end of study or prior to the start of new anti-cancer treatment (including stem cell transplant, and excluding consolidative radiotherapy) other than the study treatment. For Parts A, B, and C the response was assessed using the Revised Response Criteria for Malignant Lymphoma (Cheson 2007).
Objective response rate (ORR) per investigator was defined as the percentage of subjects with CR or PR through the end of study or prior to the start of new anti-cancer treatment (including stem cell transplant, and excluding consolidative radiotherapy) other than the study treatment. For Part D, the response was assessed using the Lugano Classification Revised Staging System for nodal non-Hodgkin and cHL (Lugano criteria) and the Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC).
Objective response rate (ORR) per investigator was defined as the percentage of subjects with CR or PR through the end of study or prior to the start of new anti-cancer treatment (including stem cell transplant, and excluding consolidative radiotherapy) other than the study treatment. For Parts E and F, the response was assessed per blinded independent central review (BICR) using the modified Lugano criteria.
Percentage of participants who achieved a best response of complete response/remission (CR), CR without hematologic recovery (CRi; leukemia only), or partial remission (PR) per the applicable response criteria. Response criteria for solid tumors (by radiographic tumor imaging) per Response Evaluation Criteria for Solid Tumors (RECIST) 1.1 (Eisenhauer 2009); response criteria for leukemia (by peripheral blood and bone marrow aspirate or biopsy) per International Working Group (Cheson 2003).
Percentage of participants treated with brentuximab vedotin monotherapy who achieved a best response of complete remission (CR, disappearance of all evidence of disease) or partial remission (PR, regression of greater than or equal to 50% of measurable disease and no new sites) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
Counts of participants who had treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose on Study SGN35-012). Serious adverse events are reported from the time of informed consent. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 4.03) were used to assess severity (1=mild, 2=moderate, 3=severe, 4=life-threatening/disabling, 5=fatal). Relatedness to study drug was assessed by the investigator (Yes/No). Participants with multiple occurrences of an adverse event within a category are counted once within the category.
Percentage of participants in the retreatment arm who achieved a best response of complete remission (CR, disappearance of all evidence of disease) or partial remission (PR, regression of greater than or equal to 50% of measurable disease and no new sites) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
Counts of participants who had adverse events or treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose on SGN35-006). Serious adverse events are reported from the time of informed consent. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 3.0) were used to assess severity (1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death). Relatedness to study drug was assessed by the investigator (Yes/No). Participants with multiple occurrences of an adverse event within a category are counted once within the category.
Counts of study participants with post-baseline laboratory abnormalities of Grade 3 or greater per NCI CTCAE version 3.0. Participants with multiple occurrences of a laboratory abnormality within a category are counted once in that category.
Percentage of participants who achieved a best response of complete remission (CR, disappearance of all evidence of disease) or partial remission (PR, regression of greater than or equal to 50% of measurable disease and no new sites) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
Treatment-emergent adverse events (TEAEs) are presented and defined as newly occurring (not present at baseline) or worsening after first dose of investigational product. The timeframe includes a 6.01 month safety reporting period and additional long-term follow up through 28.9 months.
Number of patients with complete metabolic response (CMR) at end of treatment
All AEs reported after initiation of treatment and pre-existing conditions that worsen after initiation of treatment will be considered treatment-emergent AEs (TEAEs). All AEs will be coded by system organ class, MedDRA preferred term, and severity grade using NCI CTCAE V4.03. All recorded AEs will be included in the data listings.
| Arm | Type | Description |
|---|---|---|
| Experimental Arm | EXPERIMENTAL | Brentuximab vedotin + lenalidomide + rituximab |
| Control Arm | ACTIVE_COMPARATOR | Placebo + lenalidomide + rituximab |
| CHOP | ACTIVE_COMPARATOR | cyclophosphamide, doxorubicin, vincristine, and prednisone |
| A+CHP | EXPERIMENTAL | brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone |
| Brentuximab vedotin | EXPERIMENTAL | brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion |
| Placebo | PLACEBO_COMPARATOR | placebo every 3 weeks by IV infusion |
| GDP | ACTIVE_COMPARATOR | - |
| Brentuximab vedotin + Pembrolizumab | ACTIVE_COMPARATOR | - |
| Combination Therapy | EXPERIMENTAL | brentuximab vedotin + pembrolizumab |
| Treatment (brentuximab vedotin, bendamustine) | EXPERIMENTAL | Patients receive brentuximab vedotin IV over 30 minutes on day 1 and bendamustine IV over 60 minutes on days 1 and 2. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients who respond to combination treatment and do not experience excessive toxicity may continue to receive brentuximab vedotin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity. |
| CD30-negative Cohort | EXPERIMENTAL | Participants with CD30 expression level \< 1% |
| CD30-positive Cohort | EXPERIMENTAL | Participants with CD30 expression level ≥1% to \< 10% |
| Part A: Brentuximab Vedotin in HL Patients | EXPERIMENTAL | - |
| Part B: Brentuximab Vedotin + Dacarbazine in HL Patients | EXPERIMENTAL | - |
| Part C: Brentuximab Vedotin + Bendamustine in HL Patients | EXPERIMENTAL | - |
| Part D: Brentuximab Vedotin + Nivolumab in HL Patients | EXPERIMENTAL | - |
| Part E: Brentuximab Vedotin in HL Patients | EXPERIMENTAL | - |
| Part F: Brentuximab Vedotin in PTCL Patients | EXPERIMENTAL | - |
| Brentuximab vedotin 1.8 mg/kg | EXPERIMENTAL | Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion |
| Brentuximab vedotin 2.4 mg/kg | EXPERIMENTAL | Brentuximab vedotin 2.4 mg/kg every 3 weeks by IV infusion |
| Brentuximab vedotin 1.2 mg/kg | EXPERIMENTAL | Brentuximab vedotin 1.2 mg/kg weekly, 3 out of 4 weeks, by IV infusion |
| Brentuximab vedotin+rituximab | EXPERIMENTAL | - |
| BV Retreatment | EXPERIMENTAL | Brentuximab vedotin 1.2 or 1.8 mg/kg every 3 weeks by IV infusion (retreatment after relapse) |
| BV Extension | EXPERIMENTAL | Brentuximab vedotin 1.2 or 1.8 mg/kg every 3 weeks by IV infusion (continued treatment) |
| Brentuximab Vedotin + Nivolumab | EXPERIMENTAL | Brentuximab vedotin plus nivolumab |
| Brentuximab Vedotin + Bendamustine | EXPERIMENTAL | Brentuximab vedotin 1.8 mg/kg every 3 weeks for up to 16 cycles by IV infusion and bendamustine 90 mg/m2 on Days 1 and 2 every 3 weeks by IV infusion for up to 6 cycles |
| 1 | EXPERIMENTAL | Sequential |
| 2 | EXPERIMENTAL | Combination |
| 3 Brentuximab vedotin/CH-P | EXPERIMENTAL | Combination |
| 3 | EXPERIMENTAL | brentuximab vedotin +/- ketoconazole |
| 4 | EXPERIMENTAL | special populations |
| Name | Type | Description |
|---|---|---|
| Brentuximab vedotin | DRUG | 1.2 mg/kg administered into the vein (IV; intravenously) infusion every 3 weeks |
| Rituximab | DRUG | 375 mg/m\^2 administered via intravenous infusion on Cycle 1 Day 1. 1400 mg injected under the skin (subcutaneous) permitted every 3 weeks from Cycle 2 Day 1 through end of treatment. |
| Lenalidomide | DRUG | 20 mg given by mouth (orally) daily |
| Placebo | OTHER | Administered via intravenous infusion every 3 weeks |
| doxorubicin | DRUG | 50 mg/m2 every 3 weeks by IV infusion for 6-8 cycles |
| prednisone | DRUG | 100 mg on Days 1 to 5 of each 3-week cycle, orally for 6-8 cycles |
| vincristine | DRUG | 1.4 mg/m2 (maximum 2 mg) every 3 weeks by IV infusion for 6-8 cycles |
| cyclophosphamide | DRUG | 750 mg/m2 every 3 weeks by IV infusion for 6-8 cycles |
| Gemcitabine | DRUG | 1000mg/m2 IV, 30 mins D1, D8 |
| Dexamethasone | DRUG | 40mg daily PO, D1-D4 |
| Cisplatin | DRUG | 75mg/m2 IV, 1 hour, D1 |
| Pembrolizumab | DRUG | 200mg IV, 30 mins, Q 21 days |
| Bendamustine Hydrochloride | DRUG | Given IV |
| bendamustine | DRUG | 70 mg/m\^2 by IV infusion on Days 1 and 2 of 3-week cycle |
| dacarbazine | DRUG | 375 mg/m\^2 every 3 weeks by IV infusion |
| nivolumab | DRUG | 3 mg/kg every 3 weeks by IV infusion |
| vinblastine | DRUG | 6 mg/m2 IV every 2 weeks |
| bleomycin | DRUG | 10 units/m2 IV every 2 weeks |
| rifampin | DRUG | 600 mg/day PO |
| midazolam | DRUG | 1 mg IV |
| ketoconazole | DRUG | 400 mg/day PO |
Inclusion Criteria: * Participants with relapsed or refractory diffuse and transformed large B-cell lymphoma (R/R DLBCL). DLBCL and cell of origin (GCB versus non-GCB) will be histologically determined by local pathology assessment for the purposes of study eligibility and stratification. * Partici...