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NCT01660451

Open-label, Uncontrolled Phase II Trial of Intravenous PI3K Inhibitor BAY80-6946 in Patients With Relapsed, Indolent or Aggressive Non-Hodgkin's Lymphomas

Completed Phase 2 Results posted Last updated 17 July 2024
What this trial tests

Phase 2 trial testing Copanlisib (Aliqopa, BAY80-6946) in Lymphoma, Non-Hodgkin in 227 participants. Completed in 18 May 2023.

Timeline
19 November 2012
Primary endpoint
22 June 2016
18 May 2023

Quick facts

Lead sponsorBayer
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment227
Start date19 November 2012
Primary completion22 June 2016
Estimated completion18 May 2023
Sites102 locations across Hong Kong, Italy, Finland, Ireland, Poland, South Korea, New Zealand, Russia

Drugs / interventions tested

Conditions studied

Sponsor

Bayer — full company profile →

Who can join

18 and older, any sex, with Lymphoma, Non-Hodgkin. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Objective Response Rate (ORR) Based on Independent Review-Part A Primary · Baseline up to the last patient has completed the 16 weeks of treatment

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.

GroupValue95% CI
Part A: Indolent NHL/CLL43.7528.73 – 59.68
Part A: Aggressive NHL27.0816.83 – 39.57
ORR Based on Independent Review-Part B Primary · Baseline up to the last patient has completed the 16 weeks of treatment

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.

GroupValue95% CI
Part B: Indolent NHL59.1550.60 – 67.32
ORR Based on Investigator Assessment-Part A Primary · Baseline up to the last patient has completed the 16 weeks of treatment

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.

GroupValue95% CI
Part A: Indolent NHL/CLL46.8831.54 – 62.66
Part A: Aggressive NHL31.2520.35 – 43.97
ORR Based on Investigator Assessment-Part B Primary · Baseline up to the last patient has completed the 16 weeks of treatment

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.

GroupValue95% CI
Part B: Indolent NHL51.4142.88 – 59.87
Duration of Response (DOR) Based on Independent Review-Part A Secondary · Baseline up to approximately 6 years

DOR was defined as the time from the date of the first observed tumor response of CR or PR (whichever was noted earlier) to first subsequent disease progression (either first progressive disease \[PD\], first clinical progression or first AE associated with clinical disease progression) or death caused by disease progression, if this death occurred before progression was documented. All deaths were considered as 'caused by disease progression' except deaths with the reason "other" or "AE not related to disease progression. DOR was evaluated only for patients with at least one tumor response of

GroupValue95% CI
Part A: Indolent NHL/CLL32261 – NA
Part A: Aggressive NHLNA61 – NA
DOR Based on Independent Review-Part B Secondary · Baseline up to approximately 9 years 7 months

DOR was defined as the time from the date of the first observed tumor response of CR or PR (whichever was noted earlier) to first subsequent disease progression (either first progressive disease \[PD\], first clinical progression or first AE associated with clinical disease progression) or death caused by disease progression, if this death occurred before progression was documented. All deaths were considered as 'caused by disease progression' except deaths with the reason "other" or "AE not related to disease progression. DOR was evaluated only for patients with at least one tumor response of

GroupValue95% CI
Part B: Indolent NHL14.99.2 – 22.6
DOR Based on Investigator Assessment-Part A Secondary · Baseline up to approximately 6 years

DOR was defined as the time from the date of the first observed tumor response of CR or PR (whichever was noted earlier) to first subsequent disease progression (either first progressive disease \[PD\], first clinical progression or first AE associated with clinical disease progression) or death caused by disease progression, if this death occurred before progression was documented. All deaths were considered as 'caused by disease progression' except deaths with the reason "other" or "AE not related to disease progression. DOR was evaluated only for patients with at least one tumor response of

GroupValue95% CI
Part A: Indolent NHL/CLL18956 – 574
Part A: Aggressive NHL190112 – NA
DOR Based on Investigator Assessment-Part B Secondary · Baseline up to approximately 9 years 7 months

DOR was defined as the time from the date of the first observed tumor response of CR or PR (whichever was noted earlier) to first subsequent disease progression (either first progressive disease \[PD\], first clinical progression or first AE associated with clinical disease progression) or death caused by disease progression, if this death occurred before progression was documented. All deaths were considered as 'caused by disease progression' except deaths with the reason "other" or "AE not related to disease progression. DOR was evaluated only for patients with at least one tumor response of

GroupValue95% CI
Part B: Indolent NHL11.59.2 – 16.1
Progression Free Survival (PFS) Based on Independent Review-Part A Secondary · Baseline up to approximately 6 years

PFS was defined as the time (in days) from the date of the first treatment to the date of first observed PD (radiological or clinical, or first AE associated with clinical PD, whichever was earlier) or death due to any cause (if death occurred before progression was documented).

GroupValue95% CI
Part A: Indolent NHL/CLL223147 – 546
Part A: Aggressive NHL7047 – 115
PFS Based on Independent Review-Part B Secondary · Baseline up to approximately 9 years 7 months

PFS was defined as the time (in days) from the date of the first treatment to the date of first observed PD (radiological or clinical, or first AE associated with clinical PD, whichever was earlier) or death due to any cause (if death occurred before progression was documented).

GroupValue95% CI
Part B: Indolent NHL11.38.1 – 17.6
PFS Based on Investigator Assessment-Part A Secondary · Baseline up to approximately 6 years

PFS was defined as the time (in days) from the date of the first treatment to the date of first observed PD (radiological or clinical, or first AE associated with clinical PD, whichever was earlier) or death due to any cause (if death occurred before progression was documented).

GroupValue95% CI
Part A: Indolent NHL/CLL224172 – 419
Part A: Aggressive NHL7047 – 115
PFS Based on Investigator Assessment-Part B Secondary · Baseline up to approximately 9 years 7 months

PFS was defined as the time (in days) from the date of the first treatment to the date of first observed PD (radiological or clinical, or first AE associated with clinical PD, whichever was earlier) or death due to any cause (if death occurred before progression was documented).

GroupValue95% CI
Part B: Indolent NHL10.87.2 – 12.8

Adverse events — posted to ClinicalTrials.gov

Time frame: After the first study intervention up to 35 days after the end of study intervention, Part A: approximately 6 years. Part B: approximately 9 years 7 months. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, Part A: approximately 6 years. Part B: approximately 9 years 7 months.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Part A: Indolent NHL/CLL
Serious: 16/33 (48%)
Deaths: 21/33
Part A: Aggressive NHL
Serious: 31/51 (61%)
Deaths: 39/51
Part B: Indolent NHL
Serious: 81/142 (57%)
Deaths: 75/142

Serious adverse events (113 terms)

ReactionSystemPart A: Indolent NHL/CLLPart A: Aggressive NHLPart B: Indolent NHL
PneumoniaInfections and infestations
PyrexiaGeneral disorders
HyperglycaemiaMetabolism and nutrition disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
NeutropeniaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
General physical health deteriorationGeneral disorders
Febrile neutropeniaBlood and lymphatic system disorders
Lower respiratory tract infectionInfections and infestations
Atrial fibrillationCardiac disorders
GastritisGastrointestinal disorders
NauseaGastrointestinal disorders
PancreatitisGastrointestinal disorders
CholecystitisHepatobiliary disorders
BronchitisInfections and infestations
PyelonephritisInfections and infestations
SepsisInfections and infestations
Septic shockInfections and infestations
Pneumocystis jirovecii pneumoniaInfections and infestations
Vascular device infectionInfections and infestations
Neutrophil count decreasedInvestigations
HypercalcaemiaMetabolism and nutrition disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Urinary tract obstructionRenal and urinary disorders
Acute kidney injuryRenal and urinary disorders
Other adverse events (77 terms — click to expand)

ReactionSystemPart A: Indolent NHL/CLLPart A: Aggressive NHLPart B: Indolent NHL
HyperglycaemiaMetabolism and nutrition disorders
DiarrhoeaGastrointestinal disorders
HypertensionVascular disorders
NeutropeniaBlood and lymphatic system disorders
FatigueGeneral disorders
PyrexiaGeneral disorders
NauseaGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
CoughRespiratory, thoracic and mediastinal disorders
Upper respiratory tract infectionInfections and infestations
ThrombocytopeniaBlood and lymphatic system disorders
VomitingGastrointestinal disorders
ConstipationGastrointestinal disorders
BronchitisInfections and infestations
Decreased appetiteMetabolism and nutrition disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
StomatitisGastrointestinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
PruritusSkin and subcutaneous tissue disorders
RashSkin and subcutaneous tissue disorders
Platelet count decreasedInvestigations
ChillsGeneral disorders
Oedema peripheralGeneral disorders
PneumoniaInfections and infestations
Muscle spasmsMusculoskeletal and connective tissue disorders
Abdominal pain upperGastrointestinal disorders
AstheniaGeneral disorders
HypokalaemiaMetabolism and nutrition disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Abdominal painGastrointestinal disorders
Mucosal inflammationGeneral disorders
SinusitisInfections and infestations
HypomagnesaemiaMetabolism and nutrition disorders
Productive coughRespiratory, thoracic and mediastinal disorders
NasopharyngitisInfections and infestations
RhinitisInfections and infestations
Oral herpesInfections and infestations
Weight decreasedInvestigations

Most-reported serious reactions: Pneumonia, Pyrexia, Hyperglycaemia, Pneumonitis, Neutropenia, Diarrhoea, General physical health deterioration, Febrile neutropenia.

Data from ClinicalTrials.gov NCT01660451 adverse events section.

Sponsor's own description

The objective of the study (part A) is to evaluate the efficacy and safety of BAY80-6946 in patients with indolent or aggressive Non-Hodgkin's Lymphoma, who have progressed after standard therapy. 30 patients will be enrolled to both indolent and aggressive disease group. The objective of the study part B (CHRONOS-1) is to evaluate the efficacy and safety of BAY80-6946 in patients with relapsed/refractory follicular lymphoma. 120 patients will be enrolled in the part B of the study. Further objectives are to evaluate the pharmacokinetics and biomarkers. Quality of life will be a further objective of part B of the study. In a cohort of 20 patients (enrolled both in part A and B) an ECG substudy will be performed to assess the potential for cardiac toxicity and QT/QTc interval prolongation of BAY80-6946. After an up to 28-day screening period, eligible patients will start treatment with BAY80-6946 at a dose of 0.8 mg/kg (Part A) and at a dose of 60 mg (Part B). Treatment will be continued until disease has progressed or until another criterion is met for withdrawal from study. An end-of-treatment visit will be performed within 7 days after discontinuation of study treatment. Thirty to 35 days after last study drug administration, a safety followup visit will be performed for the collection of adverse events (AEs) and concomitant medication data. Patients will be contacted quarterly to determine overall survival status up to 4 years after last patient completed treatment. Patients who discontinue study drug for reasons other than disease progression will enter the Active Assessment Follow-up period. The end of study notification to Health Authorities will be based on the completion of the collection of survival data. The efficacy is measured by the decrease in tumor size. Tumor assessments will be done at Screening, every 8 weeks during Year 1, every 12 weeks during Year 2, and every 6 months during Year 3. Blood samples will be collected for pharmacokinetic analysis. Archival tumor tissue and blood samples will be collected for biomarker analysis (mandatory) and for central pathology review (part B), fresh biopsy tissue will also be collected if available.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Targeting PI3K in cancer: mechanisms and advances in clinical trials.
    Yang J, Nie J, Ma X, Wei Y, et al · · 2019 · cited 1142× · PMID 30782187 · DOI 10.1186/s12943-019-0954-x
  2. PI3K/Akt/mTOR Pathway and Its Role in Cancer Therapeutics: Are We Making Headway?
    Peng Y, Wang Y, Zhou C, Mei W, et al · · 2022 · cited 446× · PMID 35402264 · DOI 10.3389/fonc.2022.819128
  3. Role of PI3K/AKT pathway in cancer: the framework of malignant behavior.
    Jiang N, Dai Q, Su X, Fu J, et al · · 2020 · cited 419× · PMID 32333246 · DOI 10.1007/s11033-020-05435-1
  4. PI3K inhibitors in inflammation, autoimmunity and cancer.
    Stark AK, Sriskantharajah S, Hessel EM, Hessel EM, et al · · 2015 · cited 236× · PMID 26093105 · DOI 10.1016/j.coph.2015.05.017
  5. PI3K Inhibitors in Cancer: Clinical Implications and Adverse Effects.
    Mishra R, Patel H, Alanazi S, Kilroy MK, et al · · 2021 · cited 207× · PMID 33801659 · DOI 10.3390/ijms22073464
  6. Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma.
    Dreyling M, Morschhauser F, Bouabdallah K, Bron D, et al · · 2017 · cited 198× · PMID 28633365 · DOI 10.1093/annonc/mdx289
  7. Drugging PI3K in cancer: refining targets and therapeutic strategies.
    Yap TA, Bjerke L, Clarke PA, Workman P. · · 2015 · cited 162× · PMID 26117819 · DOI 10.1016/j.coph.2015.05.016
  8. The present and future of PI3K inhibitors for cancer therapy.
    Castel P, Toska E, Engelman JA, Scaltriti M. · · 2021 · cited 152× · PMID 35118422 · DOI 10.1038/s43018-021-00218-4

Verify or expand the search:

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01660451.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing