Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Obinutuzumab · 4 trials · 5 indications
Low tumor burden is defined as absolute lymphocyte count (ALC) \< 25 × 10\^9 /L and all lymph nodes \< 5 cm per computed tomography (CT) scans.
Complete remission rate is defined as the percentage of participants achieving complete remission (CR) or complete remission with incomplete marrow recovery (CRi) as their best response based on 2008 Modified International Workshop for Chronic Lymphocytic Leukemia National Cancer Institute-Working Group (IWCLL NCI-WG) criteria. CR required all of the following: * Peripheral blood lymphocytes \<4000/μL * Absence of lymphadenopathy by physical examination and computed tomography scan * No hepatomegaly or splenomegaly * Absence of disease or constitutional symptoms (unexplained fevers \>38°C, drenching night sweats, ≥10% weight loss in last 6 months) * Blood counts above the following: * Neutrophils \>1500/μL * Platelets \>100,000/μL * Hemoglobin \>11.0 g/dL * Bone marrow at least normocellular for age, \<30% lymphocytes CRi was defined as participants with CR who had persistent cytopenia unrelated to CLL but related to drug toxicity.
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above.
MAD is defined as the highest administered dose if no maximum tolerated dose (MTD) is determined.
MTD is defined as the highest dose administered that does not result in a final determination of de-escalate at that dose level.
DLTs in this study were defined as specific adverse events (AEs) occurring during the DLT observation window: 1) Grade 4 neutropenia not responsive to granulocyte colony stimulating factors (G-CSF) lasting more than 14 days; 2) Grade 3 or 4 febrile neutropenia with fever lasting longer than 4 days; 3) Grade 4 thrombocytopenia resulting in bleeding, or that did not improve to Grade \</=2 within 3 weeks; 4) Clinical tumor lysis syndrome (TLS) defined by the presence of laboratory TLS and one or more clinical manifestations related to the electrolyte abnormalities; 5) Grade 4 infusion-related reactions (IRRs) secondary to rituximab or obinutuzumab despite appropriate premedication and administration rate; 6) All other Grades 3, 4, or 5 AEs persisting for more than 2 weeks with or without treatment with some exceptions.
| Arm | Type | Description |
|---|---|---|
| Obinutuzumab | EXPERIMENTAL | Obinutuzumab (100 mg on Day 1 of Cycle 1, 900 mg on Day 2 of Cycle 1, and 1000 mg on Days 8 and 15 of Cycle 1 and Day 1 of Cycle 2; for Cycles 3 - 6 (1000 mg on Day 1) only as needed for participants to achieve low tumor burden) was administered via intravenous infusion during the debulking regimen. After debulking, obinutuzumab (1000 mg) was administered via intravenous infusion on Day 1 of one 5-week and four 4-week cycles during the obinutuzumab/venetoclax combination part of the regimen. Venetoclax was administered according to a weekly ramp-up schedule over 5 weeks to the recommended daily dose of 400 mg. |
| Obinutuzumab/bendamustine | EXPERIMENTAL | Obinutuzumab (100 mg on Day 1 of Cycle 1, 900 mg on Day 2 of Cycle 1, and 1000 mg on Days 8 and 15 of Cycle 1 and Day 1 of Cycle 2; for Cycles 3 - 6 (1000 mg on Day 1) only as needed for participants to achieve low tumor burden) was administered via intravenous infusion during the debulking regimen. Bendamustine (90 mg/m\^2 ) was to be administered to those with nodes or nodal mass \> 10 cm, or with del(11q) and \> 5 cm nodes, or at the discretion of the investigator as above, via intravenous infusion over 10 minutes on Days 1 and 2 (or Days 2 and 3 at the discretion of the investigator during Cycle 1) of each 28-day cycle for up to 6 cycles during the debulking regimen. After debulking, obinutuzumab (1000 mg) was administered via intravenous infusion on Day 1 of one 5-week and four 4-week cycles during the obinutuzumab/venetoclax combination part of the regimen. Venetoclax was administered according to a weekly ramp-up schedule over 5 weeks to the recommended daily dose of 400 mg. |
| Part A: Cohort 1.1 ABBV-453 Dose A | EXPERIMENTAL | Participants will receive obinutuzumab during the debulking period followed escalating doses of ABBV-453, until the dose A is achieved, during the 5 year study duration. |
| 1L CLL BR+V | EXPERIMENTAL | Participants with first-line (1L)/previously untreated CLL were administered escalating doses of venetoclax (V) in combination with fixed dose bendamustine and rituximab (BR). Participants received six 28-day cycles of BR+V. Participants with 1L CLL received 6 months of single-agent venetoclax for a total of 1-year treatment duration. Single-agent venetoclax could be extended if there was detectable minimal residual disease (MRD) in the bone marrow and/or partial response (PR) after 1 year of treatment and upon the request of the treating physician. |
| 1L CLL BG+V | EXPERIMENTAL | Participants with first-line (1L)/previously untreated CLL were administered escalating doses of venetoclax (V) in combination with fixed dose bendamustine and obinutuzumab (BG). Participants received six 28-day cycles of BG+V. Participants with 1L CLL received 6 months of single-agent venetoclax for a total of 1-year treatment duration. Single-agent venetoclax could be extended if there was detectable minimal residual disease (MRD) in the bone marrow and/or partial response (PR) after 1 year of treatment and upon the request of the treating physician. |
| R/R CLL BR+V | EXPERIMENTAL | Participants with relapsed/refractory (R/R) CLL were administered escalating doses of venetoclax (V) in combination with fixed dose bendamustine and rituximab (BR). Participants received six 28-day cycles of BR+V. Participants with R/R CLL continued single-agent venetoclax until disease progression, death, or unacceptable toxicity. |
| Dose-Finding: Schedule A: Relapsed/Refractory CLL | EXPERIMENTAL | All 4 cohorts will begin venetoclax administration after the ramp-up period of 5 weeks. In 4 cohorts of participants with relapsed/refractory CLL escalating doses of venetoclax will be administered in combination with fixed dose obinutuzumab in the dose-finding stage. In Schedule A, venetoclax will be introduced before obinutuzumab. Schedule A will be explored prior to Schedule B. |
| Dose-Finding: Schedule B: Relapsed/Refractory CLL | EXPERIMENTAL | In 4 cohorts of participants with relapsed/refractory CLL escalating doses of venetoclax will be administered in combination with fixed dose obinutuzumab in the dose-finding stage. In Schedule B, venetoclax will be introduced after obinutuzumab. Schedule A will be explored prior to Schedule B. |
| Dose-Finding: Schedule A: Previously Untreated CLL | EXPERIMENTAL | All 4 cohorts will begin venetoclax administration after the ramp-up period of 5 weeks. In 4 cohorts of participants with previously untreated CLL escalating doses of venetoclax will be administered in combination with fixed dose obinutuzumab in the dose-finding stage. In Schedule A, venetoclax will be introduced before obinutuzumab. Schedule A will be explored prior to Schedule B. |
| Dose-Finding: Schedule B: Previously Untreated CLL | EXPERIMENTAL | In 4 cohorts of participants with previously untreated CLL escalating doses of venetoclax will be administered in combination with fixed dose obinutuzumab in the dose-finding stage. In Schedule B, venetoclax will be introduced after obinutuzumab. Schedule A will be explored prior to Schedule B. |
| Safety Expansion: Relapsed/Refractory CLL | EXPERIMENTAL | In participants with relapsed/refractory CLL a recommended dose of venetoclax will be administered in combination with obinutuzumab in the safety expansion stage. Schedule A or B will be used for the expansion cohort after a review of available safety data from the dose finding stage. |
| Safety Expansion: Previously Untreated CLL | EXPERIMENTAL | In participants with previously untreated CLL a recommended dose of venetoclax will be administered in combination with obinutuzumab in the safety expansion stage. Schedule A or B will be used for the expansion cohort after a review of available safety data from the dose finding stage. |
| Name | Type | Description |
|---|---|---|
| Obinutuzumab | DRUG | Administered via intravenous infusion |
| Bendamustine | DRUG | Administered via intravenous infusion |
| Venetoclax | DRUG | The venetoclax dose was administered according to a weekly ramp-up schedule over 5 weeks to the recommended daily dose of 400 mg. Venetoclax was continued for a total duration of up to 53 weeks, including the 5-week ramp-up schedule. Participants were instructed to take venetoclax tablets with a meal and water at approximately the same time each day. Venetoclax tablets were to be swallowed whole and not chewed, crushed, or broken prior to swallowing. |
| ABBV-453 | DRUG | Oral; Tablet |
| Rituximab | DRUG | Participants will receive IV infusion of rituximab (375 mg/m\^2) on Day 1 of Cycle 1 and 500 mg/m\^2 administered on Day 1 of Cycles 2-6. |
Inclusion Criteria: * Adequate hematology, kidney and liver function as described in the protocol * Diagnosis of previously untreated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) according to 2008 Modified International Workshop on Chronic Lymphocytic Leukemia National Cancer...
Obinutuzumab is used for Chronic Lymphocytic Leukemia (CLL), including relapsed/refractory or previously untreated disease. It is being studied in combination with other agents such as venetoclax and bendamustine in clinical trials. The drug is an investigational small molecule targeting MS4A1, developed by AbbVie Inc. (ABBV).
Obinutuzumab targets MS4A1, a protein also known as CD20, which is expressed on the surface of B-cells. As a binding agent, it is designed to bind to this target in the treatment of Chronic Lymphocytic Leukemia. This mechanism is being evaluated in combination therapies for CLL.
Obinutuzumab is developed by AbbVie Inc., a biopharmaceutical company traded on the New York Stock Exchange under the ticker ABBV. The company is conducting clinical trials to evaluate the drug in Chronic Lymphocytic Leukemia, including combinations with venetoclax and bendamustine.
Obinutuzumab is in Phase 1 clinical development for Chronic Lymphocytic Leukemia. It is an investigational drug, not yet approved by regulatory authorities. Clinical trials are ongoing or completed to assess its safety and efficacy in combination with other therapies for CLL.
Obinutuzumab is being studied in clinical trials including NCT01671904, a Phase 1 study of venetoclax with bendamustine plus obinutuzumab in relapsed/refractory or untreated CLL, and NCT01685892, a Phase 1 study of venetoclax with obinutuzumab in CLL. Both trials are completed.
No, Obinutuzumab is not the same as ABBV-453. Obinutuzumab is a small molecule targeting MS4A1, while ABBV-453 is a separate investigational drug being studied in a Phase 1 trial (NCT06291220) for relapsed/refractory CLL. They are distinct compounds developed by AbbVie.