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Copanlisib+ Refametinib

Phase 1

Neoplasms | Small molecule | Oncology |Bayer AG|Last Updated: Oct 11, 2017

Target and mechanism

Molecular targetPIK3CA, PIK3CD
Target classInhibitor
ModalitySmall molecule

Also known as Copanlisib

Success Probability

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Market & Valuation

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Trial Design

UNCONTROLLEDDMC
Total Trials3
Total Enrollment176

FDA Designations

No designations recorded

Clinical trial landscape

Copanlisib+ Refametinib · 3 trials · 1 indication

Phase 1 3
NCT01411410Phase I Study of PI3(Phosphoinositol 3)-Kinase Inhibitor BAY80-6946 With Paclitaxel in Patients With Advanced CancerNeoplasms
COMPLETED55 Analytics
NCT01392521Phase Ib Study of PI3(Phosphoinositol 3)-Kinase Inhibitor Copanlisib With MEK (Mitogen-activated Protein Kinase) Inhibitor Refametinib (BAY86-9766) in Patients With Advanced CancerNeoplasms
COMPLETED64 Analytics
NCT00962611BAY80-6946 Open Label, Phase I Study in Patients With Advanced CancerNeoplasms
COMPLETED57 Analytics
PHASE1COMPLETED
Phase I Study of PI3(Phosphoinositol 3)-Kinase Inhibitor BAY80-6946 With Paclitaxel in Patients With Advanced Cancer
NeoplasmsUnlock trial analytics
PHASE1COMPLETED
Phase Ib Study of PI3(Phosphoinositol 3)-Kinase Inhibitor Copanlisib With MEK (Mitogen-activated Protein Kinase) Inhibitor Refametinib (BAY86-9766) in Patients With Advanced Cancer
NeoplasmsUnlock trial analytics
PHASE1COMPLETED
BAY80-6946 Open Label, Phase I Study in Patients With Advanced Cancer
NeoplasmsUnlock trial analytics

Study Endpoints

Primary Endpoints

Adverse event collection
Up to 3 years or longer if indicated
Maximum tolerated dose, measured by adverse event profile
Up to 3 years or longer if indicated
Pharmacokinetics characterized by Cmax of BAY80-6946 (and its metabolite(s), if needed)
Multiple time points up to 6 weeks

Cmax: maximum drug concentration in plasma after single dose administration

Pharmacokinetics characterized by Cmax/D of BAY80-6946 (and its metabolite(s), if needed)
Multiple time points up to 6 weeks

Cmax/D: Cmax divided by total dose in \[mg\]

Pharmacokinetics characterized by tmax of BAY80-6946 (and its metabolite(s), if needed)
Multiple time points up to 6 weeks

tmax: time to reach maximum drug concentration in plasma after single (first) dose

Pharmacokinetics characterized by AUC(0-tlast) of BAY80-6946 (and its metabolite(s), if needed)
Multiple time points up to 6 weeks

AUC(0-tlast): AUC from time 0 to the last data point above lower limit of quantification

Pharmacokinetics characterized by AUC (if possible) of BAY80-6946 (and its metabolite(s), if needed)
Multiple time points up to 6 weeks

AUC: area under the plasma concentration vs time curve from zero to infinity

Pharmacokinetics characterized by AUC/D of BAY80-6946 (and its metabolite(s), if needed)
Multiple time points up to 6 weeks

AUC/D: AUC divided by total dose in \[mg\]

Pharmacokinetics characterized by half-life of BAY80-6946 (and its metabolite(s), if needed)
Multiple time points up to 6 weeks
Pharmacokinetics characterized by partial AUC values [eg, AUC(0-25)] of BAY80-6946 (and its metabolite(s), if needed)
Multiple time points up to 6 weeks

AUC(0-25): area under the plasma concentration vs time curve from zero to 25 h p.a.

Pharmacokinetics characterized by clearance of BAY80-6946 (and its metabolite(s), if needed)
Multiple time points up to 6 weeks
Pharmacokinetics characterized by volume of distribution of BAY80-6946 (and its metabolite(s), if needed)
Multiple time points up to 6 weeks
Estimation of percent of dose excreted [unchanged or as metabolites, if relevant) renally during 0 - 25 h after start of BAY80-6946 infusion (AE,ur(0-25)] (for Cohort 4 only)
Multiple time points up to 6 weeks

AE,ur(0-25): amount of drug excreted via urine during the collection interval 0 - 25 h

Pharmacokinetics characterized by Cmax of Paclitaxel and 6-OH paclitaxel
Multiple time points up to 6 weeks
Pharmacokinetics characterized by tmax of Paclitaxel and 6-OH paclitaxel
Multiple time points up to 6 weeks
Pharmacokinetics characterized by AUC(0-t) of Paclitaxel and 6-OH paclitaxel
Multiple time points up to 6 weeks
Pharmacokinetics characterized by AUC of Paclitaxel and 6-OH paclitaxel
Multiple time points up to 6 weeks
Pharmacokinetics characterized by half-life of Paclitaxel and 6-OH paclitaxel
Multiple time points up to 6 weeks
Pharmacokinetics characterized by clearance of Paclitaxel and 6-OH paclitaxel
Multiple time points up to 6 weeks
Pharmacokinetics characterized by volume of distribution (If possible and needed) of Paclitaxel and 6-OH paclitaxel
Multiple time points up to 6 weeks
Effect of BAY80-6946 on paclitaxel PK will be assessed by comparing Cmax of Cycle 1 Day 1 and Cycle 1 Day 15
Multiple time points up to 6 weeks
Effect of BAY80-6946 on paclitaxel PK will be assessed by comparing AUC(0-tlast) of Cycle 1 Day 1 and Cycle 1 Day 15
Multiple time points up to 6 weeks
Maximum Tolerated Dose
2 years
Comparison of the Copanlisib AUC when given alone with the AUC when given with Refametinib (BAY86-9766)
At day 15
Comparison of the Refametinib (BAY86-9766) AUC when given alone with the AUC when given with Copanlisib
At day 15
Characterize safety, tolerability + pharmacokinetics, to determine the maximum tolerated dose of BAY80-6946 administered 1x weekly for 3 weeks, every 4weeks, as a 1h-intravenous infusion. Evaluate biomarkers that may be predictive of tumor response.
2 years

Secondary Endpoints

Number of patients with mutational status
Up to 3 years or longer if indicated
Tumor Response as measured by RECIST 1.1 criteria
Up to 3 years or longer if indicated
Biomarker evaluation including analysis of pathway activation in blood and plasma
3 years
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Study Design & Arms

AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Copanlisib (BAY80-6946)EXPERIMENTALThe treatment of consists of repetitive cycles, each over 4 weeks. It continues until disease progression or limiting toxicity. If paclitaxel is discontinued for toxicity, BAY80-6946 may continue at the discretion of the investigator if a clinical benefit (response or stable disease for 6 months) is noted.
Arm 1EXPERIMENTAL -
CopanlisibEXPERIMENTAL -

Interventions

NameTypeDescription
PaclitaxelDRUGPaclitaxel (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 (BAY80-6946)DRUGBAY80-6946 (0.6 mg/kg in Cohort 1, 0.8 mg/kg in Cohort 2, 3 and 4) as 60-minute iv infusion once weekly on Days 2, 9, 16 and 23 (Day 23 in Cohort 1, 2 and 3 only) in 28-day cycles
Copanlisib + Refametinib (BAY86-9766)DRUGCopanlisib 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.
Copanlisib (Aliqopa, BAY80-6946)DRUGBAY80-6946 given IV over 1 hour every week for three weeks with a one week break until progression or unacceptable toxicities develop.
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites3

Inclusion Criteria: * Subjects must have defined tumor classification (ie, TNBC, HER2+ or Luminal) for enrollment. If tumor classification is not available the subject cannot be enrolled. Tumor classification can be based on analysis of archived tumor tissue, or analysis of tumor tissue collected a...

Countries:United StatesGermanyNetherlands
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Frequently asked questions about Copanlisib+ Refametinib

What is Copanlisib used for?

Copanlisib is an investigational small molecule being studied for the treatment of lymphoma, including non-Hodgkin lymphoma and marginal zone lymphoma, as well as other neoplasms. It is also being evaluated in healthy volunteers for research purposes. The drug is in Phase 2 clinical development for these oncology indications.

What does Copanlisib target?

Copanlisib targets PI3K, which stands for phosphoinositide 3-kinase. It belongs to the -lisib class of drugs, which are PI3K inhibitors. By inhibiting PI3K, Copanlisib is designed to interfere with signaling pathways involved in cancer cell growth and survival.

Who makes Copanlisib?

Copanlisib is being developed by Bayer AG, a multinational pharmaceutical company. Bayer AG is publicly traded under the ticker symbol BAYRY on the OTC market. The company is conducting clinical trials to evaluate the safety and efficacy of Copanlisib in various cancer indications.

What phase is Copanlisib in?

Copanlisib is currently in Phase 2 clinical development. It has completed Phase 1 trials and is being evaluated in an active Phase 2 study for marginal zone lymphoma. The drug is investigational and has not been approved by regulatory authorities for any indication.

What clinical trials is Copanlisib in?

Copanlisib has been studied in several clinical trials. NCT01392521 is a completed Phase 1 study combining Copanlisib with refametinib in advanced cancer. NCT02253420 is a completed Phase 1 drug interaction and cardiovascular safety study. NCT03474744 is an active Phase 2 trial of Copanlisib with rituximab in marginal zone lymphoma. NCT03735628 is a completed Phase 1 study with nivolumab in advanced solid tumors.

Is Copanlisib the same as BAY80-6946?

Yes, Copanlisib is also known as BAY80-6946. This alternative name appears in clinical trial records, such as NCT02253420, which is titled 'COPANLISIB (BAY80-6946) Drug-drug Interaction and Cardiovascular Safety Study.' Researchers and investors may encounter either name when reviewing the drug's development history.