Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Durvalumab · 6 trials · 6 indications
The primary efficacy analysis evaluated the complete response rate (CRR) at the end of the induction therapy in the efficacy evaluable population in a comparative manner against historical control. The response to treatment was assessed according to the 2014 International Working Group (IWG) Response Criteria for Non-Hodgkin's Lymphoma (NHL) (Cheson, 2014). CR was defined as a complete metabolic response and radiographic evidence showing target nodes/nodal masses regressed to ≤ 1.5 cm in longest diameter, no new lesions, regression of lymph nodes to normal size, absence of splenomegaly, and absence of bone marrow involvement. Clopper-Pearson two-sided 95% confidence interval is reported. Null hypothesis for the primary endpoint was rejected if the lower limit of the confidence interval for the complete response rate at the completion of the induction therapy in the efficacy evaluable population is above 55%.
Overall response rate (ORR) is defined as the percentage of participants achieving a complete remission (CR), partial remission (PR), marrow complete remission (mCR), and/or hematological improvement (HI) based on International Working Group (IWG) 2006 response criteria for MDS and central review. CR: ≤ 5% myeloblasts in bone marrow (BM), and peripheral blood: hemoglobin ≥ 11 g/dL; platelets ≥ 100 × 10⁹/L; neutrophils ≥ 1.0 × 10⁹/L; blasts 0% PR: BM blasts decreased by ≥ 50% but still \> 5%; peripheral blood as for CR mCR: BM ≤ 5% myeloblasts and decrease by ≥ 50% HI: Any of the following: •Hemoglobin increase by ≥ 1.5 g/dL or reduction of units of red blood cell (RBC) transfusions of at least 4 RBC transfusions/8 weeks compared with pretreatment •Absolute increase in platelets of ≥ 30 × 10⁹/L if pretreatment value \> 20 × 10⁹/L or increase from \< 20 × 10⁹/L to \> 20 × 10⁹/L and by at least 100% •At least 100% increase in neutrophils and an absolute increase of \> 0.5 × 10⁹/L
Overall response rate for AML is defined as the percentage of participants achieving an overall response of morphologic complete remission (CR) or morphologic complete remission with incomplete blood count recovery (CRi) based on modified IWG 2003 response criteria for AML and central review. CR: The following conditions must be met: •Absolute neutrophil count (ANC) ≥ 1.0 x10⁹/L •Platelet count ≥ 100 x10⁹/L •The bone marrow should contain less than 5% blast cells; •Auer rods should not be detectable; •No platelet, or whole blood transfusions for 7days prior to the date of the hematology assessment. CRi: Defined as a morphologic complete remission but the ANC count may be \< 1.0 x10⁹/L and/or the platelet count may be \< 100 x10⁹/L.
The overall response rate (ORR) was defined as the percentage of participants who achieved an objective response including: hematologic improvement (HI), partial remission (PR), complete remission (CR), or marrow complete remission (mCR). Hematologic response was defined as: • CR: ≤ 5% myeloblasts with normal maturation of all cell lines; peripheral blood (PB) shows: hemoglobin ≥11 g/dL, neutrophils ≥1.0x10\^9/L, platelets ≥100x10\^9/dL, blasts (0%) • PR: same as CR bone marrow (BM) shows blasts decreased by ≥ 50% over pre-treatment but still \> 5%; cellularity and morphology not relevant • mCR: BM: ≤ 5% myeloblasts and decrease by ≥ 50% over pre-treatment PB, PB: if HI responses, noted in addition to mCR • HI: HI erythroid response (HI-E); HI neutrophil response (HI-N) ; HI platelet response (HI-P)
Dose limiting toxicities were evaluated during the DLT evaluation period for participants in the dose finding cohorts. The severity grading was determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03. A DLT is defined as below: Hematologic DLT • Grade 4 neutropenia observed for greater than 5 days duration • Grade 3 neutropenia associated with fever (≥ 38.5 °C) of any duration • Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding, or any requirement for platelets transfusion • Grade 4 anemia, unexplained by underlying disease • Any other grade 4 hematologic toxicity that does not resolve to participant's pretreatment baseline level within 72 hours. Non-Hematologic DLT • Any non-hematological toxicity ≥ Grade 3 except for alopecia and nausea controlled by medical management • Any treatment interruption greater than 2 weeks due to adverse event.
Treatment-emergent adverse events (TEAEs) are defined as adverse events (AEs) occurring or worsening on or after the first dose of any study treatment (durvalumab, lenalidomide, ibrutinib, bendamustine or rituximab) and within 90 days after last dose of durvalumab or 28 days after the last dose of other study drugs, whichever was later, as well as those serious adverse events made known to the investigator at any time thereafter that were suspected of being related to study treatment. The intensity of AEs was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. For all other AEs not described in the CTCAE criteria, the intensity was assessed by the investigator as mild (Grade 1), moderate (Grade 2), severe (Grade 3), life-threatening (Grade 4), or death (Grade 5).
A Dose Review Team (DRT) evaluated DLTs to determine the recommended dose (RD) of Durvalumab to use in the Expansion Period. A DLT was defined as: a. Grade 4 neutropenia for \>= 5 days. b. Grade 3 neutropenia associated with fever (≥ 38.5°C / 101.3°F) of any duration. c. Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding, or platelets transfusion. d. Grade 4 hematologic toxicity that does not resolve to baseline level \<=72 hours. e. Grade 4 anemia, unexplained by underlying disease. f. Any nonhematologic toxicity Grade ≥ 3 except for alopecia and nausea. g. Treatment interruption \>= 2 weeks due to AE. If ≤ 1 of the 6 initial participants in each cohort experience a DLT during cycle 1, the RD was Durvalumab 1500 mg; If \>=2 of the 6 initial participants in any cohort experience a DLT during cycle 1, the maximum tolerated dose (MTD) was exceeded and the dose level of Durvalumab was de-escalated to 750 mg
Number of participants with DLTs in the first cycle of treatment
| Arm | Type | Description |
|---|---|---|
| DUR + R-CHOP | EXPERIMENTAL | On Day 1 of each 21-day cycle, participants received durvalumab 1125 mg intravenously (IV) followed by R-CHOP (IV rituximab 375 mg/m\^2, doxorubicin 50 mg/m\^2, vincristine 1.4 mg/m\^2 (maximum dose of 2.0 mg total), and cyclophosphamide 750 mg/m\^2); Participants also were administered daily oral or IV prednisone/prednisolone 100 mg from Day 1 to 5. Induction treatment continued for a total of 6-8 cycles. Participants who achieve a complete response or partial response continue with consolidation therapy treatment consisting of durvalumab monotherapy 1500 mg by IV on Day 1 of each 28-day cycle for up to a total of 12 months. |
| DUR + R2-CHOP | EXPERIMENTAL | Participants start the study on durvalumab in combination with R-CHOP (as described in Arm DUR + R-CHOP). Based on their DLBCL Cell-of-Origin subtype (test typically done between cycles 1 and 2), participants with ABC subtype continue the study taking durvalumab in combination with R2-CHOP. On Day 1 of each 21-day cycle, participants received durvalumab 1125 mg intravenously (IV) followed by R-CHOP. Participants were also administered daily oral or IV prednisone/prednisolone 100 mg from Day 1 to 5. In addition, a daily oral lenalidomide 15 mg was administered from Day 1 to 14 of each 21-day cycle. Induction treatment continued for a total of 6-8 cycles. Participants who achieve a complete response or partial response continue with consolidation therapy treatment consisting of durvalumab monotherapy 1500 mg by IV on Day 1 of each 28-day cycle for up to a total of 12 months. Enrollment into Arm B was discontinued. |
| Azacitidine + Durvalumab | EXPERIMENTAL | Participants received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met. |
| Azacitidine Alone | ACTIVE_COMPARATOR | Participants received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met. |
| Monotherapy: Oral Azacitidine | EXPERIMENTAL | Oral azacitidine (AZA) 100 mg, 150 mg, or 200 mg tablets twice daily (BID) on days 1 to 21 of each 28-day treatment cycle. Participants continued to receive their assigned study treatment unless disease progression, unacceptable toxicity, lost to follow-up or withdrawal by participant occurred. |
| Combination Therapy: Oral Azacitidine and Durvalumab | EXPERIMENTAL | Oral Azacitidine 100 mg oral azacitidine tablets BID on days 1 to 14 or days 1 to 21 of each 28-day treatment cycle and durvalumab 1500 mg by intravenous (IV) infusion on day 1 of each 28-day treatment cycle; participants continued to receive their assigned study treatment unless disease progression, unacceptable toxicity, lost to follow-up or withdrawal by participant occurred. |
| Arm A: Durvalumab + Lenalidomide ± Rituximab | EXPERIMENTAL | Participants assigned to Arm A will receive: * Durvalumab 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13 (ie, 12 months) and * Lenalidomide orally at assigned dose levels (10 mg, 15 mg or 20 mg) once daily on Days 1 to 21 of: * Cycles 1 through 13 in indolent non-Hodgkin's lymphoma (NHL) or * All cycles of treatment period until disease progression, unacceptable toxicity, or discontinuation for any other reason in aggressive NHL * Rituximab 375 mg/m² IV infusion every week in Cycle 1 (Days 2, 8, 15, 22) and on Day 1 of Cycles 2 through 5. All treatment cycles were 28 days. |
| Arm B: Durvalumab + Ibrutinib | EXPERIMENTAL | Participants assigned to Arm B will receive: * Durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 * Ibrutinib orally at assigned dose levels (280 mg, 420 mg, or 560 mg) once daily until disease progression, unacceptable toxicity or discontinuation for any other reason. All treatment cycles were 28 days. |
| Arm C: Durvalumab + Rituximab ± Bendamustine | EXPERIMENTAL | Participants assigned to Arm C will receive: * Durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 * Rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose will be 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose) * Bendamustine IV infusion at assigned dose levels (70 mg/m² or 90 mg/m²) on Days 1 and 2 of Cycles 1 through 6. All treatment cycles were 28 days. |
| Arm D: Durvalumab Monotherapy | EXPERIMENTAL | Participants assigned to Arm D will receive durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13. All treatment cycles were 28 days. |
| Cohort A: High risk, TNE | EXPERIMENTAL | High risk, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were administered * Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle * Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\]) value on Days 1 to 21 of each 28-day treatment cycle * Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle |
| Cohort B: >=65 years old, TNE | EXPERIMENTAL | \>= 65 years old, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were not high risk were administered * Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle * Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\]) value on Days 1 to 21 of each 28-day treatment cycle * Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle, up to 12 cycles |
| Cohort C: High risk, Post-transplant | EXPERIMENTAL | High risk, post-transplant NDMM participants were administered the following as maintenance therapy: * Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle * Oral lenalidomide (LEN) 10 mg/day on Days 1 to 21 of each 28-day treatment cycle |
| Durvalumab monotherapy | EXPERIMENTAL | Intravenous (IV) durvalumab at assigned dose level (750, 1500, 2250, or 3000 mg) over 1 hour on day 1 of a 28-day cycle |
| Durvalumab + pomalidomide (POM) | EXPERIMENTAL | IV durvalumab at assigned dose level (750, 1500, 2250, or 3000 mg) over 1 hour on day 1 of a 28-day cycle and Oral POM 4 mg/day on Days 1 to 21 of each 28-day treatment cycle |
| Durvalumab + pomalidomide (POM) + dexamethasone (dex) | EXPERIMENTAL | IV durvalumab at assigned dose level (750, 1500, 2250, or 3000 mg) over 1 hour on day 1 of a 28-day cycle with Oral POM 4 mg/day on Days 1 to 21 of each 28-day treatment cycle and Oral dex 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of a 28-day cycle |
| Name | Type | Description |
|---|---|---|
| Durvalumab | DRUG | Durvalumab was supplied in single use vials as a liquid solution containing 500 mg (nominal) of durvalumab at a concentration of 50 mg/mL to be infused by intravenous (IV) injection. Day 1 of each treatment cycle (Induction Period and Consolidation Period) started with the administration of IV durvalumab followed by a 2-hour observation period post infusion. |
| Rituximab | DRUG | Subsequent to durvalumab infusion, rituximab was administered by IV. Rituximab administration could be split over 2 consecutive days according to local clinical practice. Rapid infusion of rituximab was not allowed in this clinical study. |
| Doxorubicin | DRUG | A component of the CHOP therapy administered by IV. CHOP therapy was administered following rituximab. |
| Vincristine | DRUG | A component of the CHOP therapy administered by IV. CHOP therapy was administered following rituximab. |
| Cyclophosphamide | DRUG | A component of the CHOP therapy administered by IV. CHOP therapy was administered following rituximab. |
| Prednisone | DRUG | Prednisone was administered as an IV infusion or by mouth (PO) on Day 1, followed by PO administration on Days 2-5 of each cycle. Prednisone could be given prior to other drugs of the CHOP therapy. It was administered after lenalidomide dosing in the R2-CHOP treatment arm. |
| Lenalidomide | DRUG | Lenalidomide was administered orally in capsule form on Days 1-14 of the DUR+R2-CHOP treatment arm only. |
| Azacitidine | DRUG | Administered by subcutaneous injection on Days 1 to 7 of each 4-week treatment cycle. |
| Oral Azacitidine | DRUG | Oral azacitidine (AZA) 100 mg, 150 mg, or 200 mg tablets twice daily (BID) on days 1 to 21 of each 28-day treatment cycle. Participants continued to receive their assigned study treatment unless disease progression, unacceptable toxicity, lost to follow-up or withdrawal by participant occurred. |
| Ibrutinib | DRUG | Administered orally |
| Bendamustine | DRUG | Administered as a 30-minute intravenous infusion |
| Dexamethasone | DRUG | tablets for oral administration |
| Pomalidomide | DRUG | - |
Inclusion Criteria: 1. CD20+Diffuse Large B-Cell Lymphoma. 2. Ann Arbor stage 3 or 4 or stage 2 with bulky disease 3. High or high-intermediate disease risk. 4. No prior anti-lymphoma treatment. 5. Subject is willing and able to undergo biopsy. 6. Investigator considers R-CHOP immunochemotherapy ap...
Durvalumab is an investigational monoclonal antibody being studied for use in blood cancers including acute myeloid leukemia, multiple myeloma, myelodysplastic syndromes, and diffuse large B-cell lymphoma. It is currently in Phase 2 clinical development for these oncology indications.
Durvalumab is being developed by Bristol-Myers Squibb Company, which trades under the ticker BMY. The company is conducting clinical trials of Durvalumab in multiple myeloma and diffuse large B-cell lymphoma.
Durvalumab is in Phase 2 clinical development. It has completed two Phase 2 trials and two Phase 1 trials, with a total of 213 patients enrolled across all studies. It remains investigational and is not yet approved.
Durvalumab has completed four clinical trials. NCT02281084 studied it in myelodysplastic syndromes, NCT02616640 and NCT02685826 studied it in multiple myeloma, and NCT03003520 studied it in diffuse large B-cell lymphoma. All trials are completed.
Yes, Durvalumab is a monoclonal antibody, classified as a -mab antibody. It is being evaluated as a treatment for hematologic malignancies including multiple myeloma and lymphoma.