Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Copanlisib (BAY80-6946), Aliqopa
Copanlisib · 15 trials · 13 indications
Adverse event data were collected after signing the informed consent until 30 days after the last study drug administration (end of safety follow-up)
Serious adverse event data were collected after signing the informed consent until 30 days after the last study drug administration (end of safety follow-up)
\- Above threshold of 10% and reported as TEAEs - any event (Grade 1-4)
\- Reported as TEAEs - worst CTCAE grade total -
Progression-free survival (PFS) was defined as the time from randomization to progressive disease (PD) or death due to any cause, whichever was earlier according to the Lugano Classification and Response criteria in patients affected by Waldenström macroglobulinemia (kindly refer to the links in the Protocol section).
Primary endpoint is the complete response (CR rate (CRR) determined 12 months after start of induction therapy). Patients who progress before 12 months after start of treatment will be treated as CR='NO' and will be included in the calculation of the primary endpoint. No primary endpoint will be determined for patients who withdraw.
The objective response rate (ORR) was defined as the percentage of participants who had at least one post-baseline overall response of complete response (CR) or partial response (PR) during study conduct according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT. The primary efficacy overall response assessment was based on investigator assessment of response.
The objective response rate (ORR) was defined as the percentage of participants who had at least one post-baseline overall response of complete response (CR) or partial response (PR) during study conduct according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT. The primary efficacy overall response assessment was based on investigator assessment of response.
The objective response rate (ORR) was defined as the percentage of participants who had at least one post-baseline overall response of complete response (CR) or partial response (PR) during study conduct according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT. The primary efficacy overall response assessment was based on investigator assessment of response.
Objective response rate was defined as the proportion of participants with a best response rating of complete response (CR), unconfirmed complete response (CRu) or partial response (PR), based on the Report of an International Workshop to Standardize Response Criteria for non-Hodgkins Lymphomas, Cheson, 1999, as evaluated by the Independent Response Adjudication Committee (IRAC). For chronic lymphocytic leukemia (CLL) patients Hallek criteria (2008) were used and assessed by investigator.
Objective response rate was defined as the proportion of participants with a best response rating of CR or PR, based on the International Working Group Revised response Criteria for Malignant Lymphoma, Cheson 2007.
Objective response rate was defined as the proportion of participants with a best response rating of CR, CRu or PR, based on the Report of an International Workshop to Standardize Response Criteria for non-Hodgkins Lymphomas, Cheson, 1999. For CLL patients Hallek criteria (2008) were used and assessed by investigator.
Objective response rate was defined as the proportion of participants with a best response rating of CR or PR, based on the International Working Group Revised response Criteria for Malignant Lymphoma, Cheson 2007.
Cmax: maximum observed drug concentration in measured matrix after single dose administration
AUC: area under the concentration vs. time curve from zero to infinity after single (first) dose
Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
AUC refers to area under the concentration vs time curve from 0 to infinity which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
AUC(0-168) refers to AUC from time 0 to 168 hr which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
The NCI Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0) will be used to assess the intensity of AE
OR: Best response rating of complete response or partial response according to the criteria defined in the Revised Response Criteria for Malignant Lymphoma(JClin Oncol.2007 Feb)
AUC (0-168): Area under the curve from dosing to 168 h after dosing
AUC: Area under the curve
Cmax: Maximum concentration attained after dosing
QTcF: Time-matched largest change of QT interval (Frederica's correction)
Cmax: maximum drug concentration in plasma after single dose administration
Cmax/D: Cmax divided by total dose in \[mg\]
tmax: time to reach maximum drug concentration in plasma after single (first) dose
AUC(0-tlast): AUC from time 0 to the last data point above lower limit of quantification
AUC: area under the plasma concentration vs time curve from zero to infinity
AUC/D: AUC divided by total dose in \[mg\]
AUC(0-25): area under the plasma concentration vs time curve from zero to 25 h p.a.
AE,ur(0-25): amount of drug excreted via urine during the collection interval 0 - 25 h
| Arm | Type | Description |
|---|---|---|
| Copanlisib (BAY 80-6946) | EXPERIMENTAL | patients with rituximab-refractory iNHL |
| Copanlisib + Rituximab | EXPERIMENTAL | Combination of the Copanlisib and rituximab |
| Placebo + Rituximab | PLACEBO_COMPARATOR | Combination of Copanlisib placebo and rituximab |
| Experimental Arm | EXPERIMENTAL | Induction Phase: Cycle 1-6 (28 days cycle): Copanlisib: 60 mg i.v. fixed dose days 1, 8, 15. Rituximab: 375 mg/m2 day 1 i.v. Maintenance: Start 2 months after start of the last induction cycle for patients at least achieving a stable response after induction. Copanlisib: 60 mg i.v. fixed dose day 1 and day 15 every 4 weeks for a maximum of 12 cycles or until progression or study drug-related intolerable toxicity (month 2 to month 13 after end of induction). Rituximab: 375 mg/m2 i.v. day 1 every 8 weeks for a maximum of 12 infusions or until progression or study drug-related intolerable toxicity (month 2 to month 24 after end of induction) |
| Copanlisib (Aliqopa, BAY80-6946) | EXPERIMENTAL | Copanlisib (Aliqopa, BAY80-6946) solution for IV infusion (test drug/investigational medicinal product) |
| Copanlisib (indolent NHL) | EXPERIMENTAL | Part A: Participants in this arm will be patients with indolent NHL. |
| Copanlisib (aggressive NHL) | EXPERIMENTAL | Part A: Participants in this arm will be patients with aggressive NHL. |
| Copanlisib (indolent B-cell NHL) | EXPERIMENTAL | Part B: Participants in this arm will be patients with indolent B-cell NHL. |
| Copanlisib and Ibrutinib | EXPERIMENTAL | Copanlisib is given intravenously on days 1, 8, and 15 of 28 day cycles. Ibrutinib is given orally every day on 28 days cycles. The maximum duration of treatment is 36 cycles not exceeding 36 months. In the phase II study, the cohort will expand and accrue patients at the recommended phase II dose of copanlisib and ibrutinib determined during phase I dose escalation. In a simon two stage mini-max design, an initial 18 patients will be enrolled, inclusive of 6 patients treated at MTD or RP2D from phase I study, in first stage. |
| Dose escalation | EXPERIMENTAL | Copanlisib: 45 mg (dose level -1) or 60 mg (dose level 1) on Day 1, Day 8 and Day 15 (28 day cycle) Nivolumab: 240 mg on Day 15 of Cycle 1 and on Day 1 and Day 15 of subsequent cycles (28 day cycle). |
| Dose expansion | EXPERIMENTAL | Copanlisib: Recommended phase 2 dose established in the phase 1b part on Day 1, Day 8 and Day 15 (28 day cycle) Nivolumab: 240 mg on Day 15 of Cycle 1 and on Day 1 and Day 15 of subsequent cycles (28 day cycle). |
| BAY80-6946/Healthy subject | EXPERIMENTAL | Healthy subjects |
| BAY80-6946/moderate hepatically impaired patients | EXPERIMENTAL | Patients with Child-Pugh B (score 7-9) at the screening visit |
| BAY80-6946/severe renal impaired patients | EXPERIMENTAL | Patients with eGFR 15-29 mL/min/1.73 m\^2 at the screening visit based on the Modification of Diet in Renal Disease (MDRD) equation |
| BAY80-6946/severe hepatically impaired patients | EXPERIMENTAL | Patients with Child-Pugh C (score 10-15) at the screening visit |
| Copanlisib (BAY80-6946) | EXPERIMENTAL | Dose escalation/safety evaluation cohort and objective tumor response (OR) expansion cohort |
| Copanlisib with and without concomitant Itraconazole (Arm A) | EXPERIMENTAL | To evaluate the effect of Itraconazole on the pharmacokinetics of Copanlisib (BAY80-6946) and safety in patients with advanced solid tumor. Cycle 1 of the study will be conducted in 2 parts: Part 1 and part 2: * Part 1 of Cycle 1: 6 patients will be enrolled and will receive 12 mg of copanlisib on Day 1 and Day 15. Itraconazole 200 mg will be administered twice a day on Day 12 and then once daily from Days 13 to 21. * Part 2 of Cycle 1: 20 patients will be enrolled and receive copanlisib doses of either 12 mg, 30 mg or 60 mg on Days 1 and 15 with the same dose administered on both days. Copanlisib dose for Part 2 will be based on safety and copanlisib pharmacokinetics in Part 1. Itraconazole 200 mg will be administered twice a day on Day 12 and then once daily from Days 13 to 21. * Cycle 2 and subsequent cycles: All patients will receive copanlisib doses of 60 mg on Days 1, 8 and 15. |
| Copanlisib with and without concomitant Rifampin (Arm B) | EXPERIMENTAL | To evaluate the effect of Rifampin on the pharmacokinetics of Copanlisib (BAY 80-6946) and safety in patients with advanced solid tumor or non-Hodgkin's lymphoma in Cycle 1. Approximately 30 subjects will receive 60mg of copanlisib on Cycle 1 Day 1 and Cycle 1 Day 15. Rifampin will be administered once a day from Cycle 1 Day 10 to Day 21. Holter monitoring will be performed on Cycle 1 Day -1 and Cycle 1 Day 1 to evaluate the effect of copanlisib on the QT/QTc assessment. Cycle 2 and subsequent cycles, all patients will receive copanlisib dose of 60 mg on Days 1, 8 and 15. Holter monitoring will be performed on Cycle 3 Day 1 and Cycle 6 Day 1. |
| Arm 1 | EXPERIMENTAL | 0.8 mg/kg body weight and 0.4 mg/kg (not to exceed 65 mg) for the non-diabetic patients |
| Arm 2 | EXPERIMENTAL | 45 mg and 60 mg for the diabetic patients |
| Copanlisib | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Copanlisib (BAY 80-6946) | DRUG | 60 mg of experimental drug in solution administered intravenously on Days 1, 8 and 15 of each 28-day treatment cycle |
| Copanlisib (Aliqopa, BAY80-6946) | DRUG | Copanlisib is supplied as lyophilized preparation in a 6 mL injection vial. The total amount of copanlisib per vial is 60 mg. The solution for IV infusions is obtained after reconstitution with normal saline solution. Dosing will be administered on Days 1, 8 and 15 of each 28-day cycle. Copanlisib will be administered before rituximab. |
| Placebo | DRUG | Placebo is supplied as lyophilized preparation in a 6 mL injection vial. The developed placebo lyophilisate is equivalent to the 60 mg copanlisib formulation, with regard to the composition of excipients and the instructions for reconstitution and dose preparation. Placebo dosing will be administered on Days 1, 8 and 15 of each 28-day cycle. Placebo will be administered before rituximab. |
| Rituximab | DRUG | Rituximab dose 375 mg/m2 body surface weekly during Cycle 1 on Days 1, 8, 15 and 22, and then on Day 1 of Cycles 3, 5, 7 and 9.The solution for IV infusions is obtained after reconstitution of a calculated concentration of 1 to 4 mg/ml rituximab into an infusion bag containing sterile, pyrogen-free sodium chloride 9 mg/ml (0.9%) solution for injection or 5% D-Glucose in water. |
| Copanlisib | DRUG | Solution for IV infusion |
| Ibrutinib | DRUG | Oral ibrutinib daily in 28 day cycles. A cycle is defined as 28 days of therapy. |
| Nivolumab | DRUG | Nivolumab: concentrate for solution for infusion |
| Copanlisib (BAY80-6946) | DRUG | Dosing is weekly for the first 3 weeks (on Days 1, 8, and 15) of a 28-day cycle, followed by a 1-week break (i.e., no infusion on Day 22). |
| Itraconazole | DRUG | Cycle 1 Day 12: 2 x 200 mg itraconazole oral (two doses, 12 hours apart) Cycle 1 Days 13-21: 200 mg itraconazole oral, once daily in the morning |
| Rifampin | DRUG | Cycle 1 Days 10 - 21: 600mg Rifampin oral, once daily in the morning |
| Paclitaxel | DRUG | Paclitaxel (80 mg/m2 in Cohort 1, 2 and 3, 90 mg/m2 in Cohort 4) as 60-minute iv infusion once weekly on Days 1, 8, 15 and 22 (Day 22 in Cohort 1, 2 and 3 only) in 28-day cycles * The following intravenous premedications are required 30 to 60 minutes before paclitaxel infusion: Dexamethasone (10 mg), diphenhydramine (50 mg) and either cimetidine (300 mg) or ranitidine (50 mg) * Alternatively, for premedications other than dexamethasone, the standard institutional regimen is permitted. |
| Copanlisib + Refametinib (BAY86-9766) | DRUG | Copanlisib will be administered as an IV infusion weekly for 3 weeks in combination with Refametinib (BAY86-9766) at varying dose levels. Refametinib (BAY86-9766) is administered orally twice a day starting at Day 4 of Cycle 1. |
Inclusion Criteria: * Histologically confirmed diagnosis of indolent B-cell NHL, with histological subtype limited to the following: * Follicular lymphoma (FL) grade 1-2-3a. * Small lymphocytic lymphoma (SLL) with absolute lymphocyte count \< 5 x 10\*9/L at the time of diagnosis and at study e...
Copanlisib is an investigational small molecule studied in lymphoma and solid tumor settings, including diffuse large B-cell lymphoma, mantle cell lymphoma, marginal zone lymphoma, and non-Hodgkin lymphoma. It has also been evaluated in hepatic and renal insufficiency studies and in medical oncology research. It is being developed by Bayer AG.
Copanlisib targets PIK3CA and PIK3CD, which are catalytic subunits of phosphoinositide 3-kinase (PI3K). It acts as an inhibitor of these targets. This mechanism places it in the PI3K inhibitor class of small molecule oncology agents.
Copanlisib is developed by Bayer AG, which trades under the ticker BAYRY. Bayer is the sponsor behind the clinical development program for this PI3K inhibitor across lymphoma and solid tumor indications.
Copanlisib is in Phase 2 development. It is an investigational agent and has not been approved by the FDA for the indications studied. The program includes completed Phase 1 trials and one active Phase 2 trial that is no longer recruiting.
Copanlisib has been studied in several trials, including NCT03877055 in mantle cell lymphoma with ibrutinib, NCT03735628 in advanced solid tumors with nivolumab, NCT03498430 in non-Hodgkin lymphoma, and NCT03474744 in marginal zone lymphoma with rituximab. Total enrollment across the program is 811 patients.
Yes. Copanlisib is also known as BAY80-6946 and by the brand name Aliqopa. It has additionally been studied in combination with refametinib, also called BAY86-9766. These names refer to the same compound or its combination regimen.