Copanlisib* Clinical Trials

Learn about ongoing and planned studies investigating copanlisib in patients with
relapsed/refractory indolent non-Hodgkin's lymphomas (iNHL),
diffuse large B-cell lymphoma (DLBCL), and mantle cell lymphoma (MCL).

COPANLISIB TRIALS
*Copanlisib is an investigational agent currently in clinical trials and is not approved by the FDA, EMA, or other health authorities. The efficacy and safety of copanlisib has not been established, and this information is being provided only for the purpose of providing an overview of clinical trials for recruitment.
Copanlisib is an investigational agent currently in clinical trials and is not approved by the FDA, EMA, or other health authorities. The efficacy and safety of copanlisib has not been established, and this information is being provided only for the purpose of providing an overview of clinical trials for recruitment.
This site contains information about copanlisib clinical trials.
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1-844-229-3710Bayer@emergingmed.com

Ongoing Clinical Trials With Copanlisib

phase

DESCRIPTION

RECRUITING STATUS

DISEASE of Interest

Phase II
Open-label, uncontrolled phase II trial of intravenous PI3K inhibitor copanlisib in patients with relapsed, indolent, or aggressive non-Hodgkin's lymphomas (NHL). (NCT01660451)
Active, not enrolling
Indolent or Aggressive Non-Hodgkin’s Lymphoma

Primary Outcome Measure:

  • Objective response rate (ORR)

Secondary Outcome Measures:

  • Duration of response (DoR) after 12 months and after 3 years
  • Overall survival (OS) after 12 months and after 3 years
  • Progression-free survival (PFS) after 12 months and after 3 years
  • Safety and tolerability
  • Duration of response after study withdrawal

Selected Inclusion Criteria:

  • Histologically confirmed indolent or aggressive NHL
  • Part A: Relapsed or refractory to ≥2 prior chemotherapy and/or immunotherapy treatments
  • Part B: Relapsed or refractory to ≥2 prior lines of therapy; patients must have received rituximab and alkylating agents
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤2
  • Life expectancy of at least 3 months
  • Adequate bone marrow, liver, and renal function

Selected Exclusion Criteria:

  • Uncontrolled hypertension, concurrent, or history of bleeding diathesis or interstitial lung disease
  • Prior treatment with PI3K inhibitors
  • Type I or II diabetes mellitus with HbA1c >8.5% or fasting plasma glucose >160 mg/dL at screening

For complete information please visit: http://www.clinicaltrials.gov (NCT01660451)

Phase III
CHRONOS-2: A phase III study of copanlisib vs placebo in rituximab-refractory indolent non-Hodgkin's lymphoma. (NCT02369016)
Now enrolling
Indolent Non-Hodgkin’s Lymphoma

Primary Outcome Measure:

  • Progression free survival (PFS)

Secondary Outcome Measures:

  • Time to deterioration in disease - related symptoms
  • Safety and tolerability
  • Objective tumor response rate (ORR), duration of response (DOR), complete response rate (CRR), overall survival (OS), time to improvement in DRS-P

Selected Inclusion Criteria:

  • Patients ≥18 years with histologically confirmed diagnosis of indolent B-cell NHL (limited to: FL, SLL, LPL/WM, MZL)
  • Patients must have received 2 or more prior lines of treatment
  • Prior therapy must include rituximab and alkylating agents
  • Refractory to rituximab

Selected Exclusion Criteria:

  • Histologically confirmed diagnosis of FL grade 3b
  • Chronic lymphocytic leukemia (CLL)
  • Histological confirmation of disease transformation
  • Bulky disease — Lymph nodes or tumor mass (except spleen) ≥7cm LD
  • Type I or II diabetes mellitus with HbA1c >8.5%

FL=follicular lymphoma; SLL=small lymphocytic lymphoma; MCL=mantle cell lymphoma; LPL/WM=lymphoplasmacytic lymphoma/Waldenström’s macroglobulinemia;
MZL=marginal zone lymphoma

For complete information please visit: http://www.clinicaltrials.gov (NCT02369016)

Phase III
CHRONOS-3: A phase III study of copanlisib in combination with rituximab in relapsed indolent NHL. (NCT02367040)
Now enrolling
Indolent Non-Hodgkin’s Lymphoma

Primary Outcome Measure:

  • Progression free survival (PFS)

Secondary Outcome Measures:

  • Objective response rate (ORR), duration of response (DOR), complete response, time to progression (TTP), overall survival (OS), quality of life (QoL)
  • Safety and tolerability

Selected Inclusion Criteria:

  • Patients ≥18 years with histologically confirmed diagnosis of CD20 positive Indolent non-Hodgkin’s lymphoma (limited to: FL grade1-2-3a, SLL, LPL/WM, MZL)
  • Relapsed after ≥1 prior line of rituximab-containing therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤2
  • Availability of fresh tumor tissue and/or archival tumor tissue at screening
  • Treatment-free interval after the last rituximab-based treatment of ≥12 months or contraindication for chemotherapy (eg, age, comorbidities, residual toxicities) with treatment-free interval after the last rituximab-based treatment of ≥6 months

Selected Exclusion Criteria:

  • Histologically confirmed diagnosis of FL grade 3b or disease transformation, or CLL
  • Type I or II diabetes mellitus with HbA1c >8.5% or fasting plasma glucose >160 mg/dL at screening
  • Documented evidence of resistance to prior treatment with idelalisib or other PI3K inhibitors

FL=follicular lymphoma; SLL=small lymphocytic lymphoma; MCL=mantle cell lymphoma; LPL/WM=lymphoplasmacytic lymphoma/Waldenström’s macroglobulinemia;
MZL=marginal zone lymphoma

For complete information please visit: http://www.clinicaltrials.gov (NCT02367040)

Phase III
CHRONOS-4: A phase III study of copanlisib in combination with standard immunochemotherapy in relapsed indolent NHL. (NCT02626455)
Now enrolling
Indolent Non-Hodgkin’s Lymphoma

Primary Outcome Measure:

  • Safety run-in: Determination of the recommended Phase III dose of copanlisib in combination with standard immunochemotherapy assessed by the occurrence of dose-limiting toxicities and adverse events
  • Phase III: To evaluate copanlisib in combination with standard immunochemotherapy, compared to standard immunochemotherapy assessed by progression free survival (PFS)

Secondary Outcome Measures:

  • Objective tumor response rate (ORR), duration of tumor response (DOR), complete tumor response rate (CRR), time to tumor progression (TTP), overall survival (OS), quality of Life (QoL)
  • Safety and tolerability

Selected Inclusion Criteria:

  • Patients ≥18 years with histologically confirmed diagnosis of CD20 positive indolent NHL (limited to: FL G1-2-3a, SLL, LPL/WM, MZL)
  • Relapsed after ≥1 prior line of therapy, including rituximab and alkylating agents
  • Previous exposure to PI3K is acceptable provided there is no resistance
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤2
  • Availability of fresh tumor tissue and/or archival tumor tissue at Screening

Selected Exclusion Criteria:

  • Histologically confirmed diagnosis of FL grade 3b, transformed disease, or CLL
  • Rituximab resistance at any line of therapy
  • Type I or II diabetes mellitus with HbA1c >8.5% or fasting plasma glucose >160 mg/dL at screening
  • Uncontrolled hypertension

FL=follicular lymphoma; SLL=small lymphocytic lymphoma; MCL=mantle cell lymphoma; LPL/WM=lymphoplasmacytic lymphoma/Waldenström’s macroglobulinemia;
MZL=marginal zone lymphoma

For complete information please visit: http://www.clinicaltrials.gov (NCT02626455)

Phase II
Phase II copanlisib in relapsed/refractory diffuse large B-cell lymphoma (DLBCL). (NCT02391116)
Active, not enrolling
Aggressive Non-Hodgkin's Lymphoma

Primary Outcome Measure:

  • Objective response rate (ORR) to assess relationship between efficacy and potentially predictive biomarker

Secondary Outcome Measures:

  • Duration of response (DOR)
  • Progression-free survival (PFS)
  • Overall survival (OS)
  • Disease control rate (DCR)
  • Duration of stable disease (DOSD)
  • Safety and tolerability

Selected Inclusion Criteria:

  • Patients ≥18yrs with histologically confirmed diagnosis of DLBCL, or DLBCL transformed from follicular lymphoma
  • Patients must have received one or more prior lines of treatment
  • Prior therapy must include CHOP + rituximab or equivalent regimen
  • Patients must have measurable disease

Selected Exclusion Criteria:

  • Active CTCAE grade 3/4 infection
  • Hepatitis B or hepatitis C
  • Known history of HIV infection
  • Current CNS involvement by lymphoma
  • Uncontrolled arterial hypertension despite optimal medical management
  • Type I or II diabetes mellitus with HbA1c >8.5% at screening
  • History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function (as judged by the investigator)

For complete information please visit: http://www.clinicaltrials.gov (NCT02391116)

Phase II
A phase IIa study of copanlisib in relapsed or refractory mantle cell lymphoma (MCL). (NCT02455297)
Now enrolling
Aggressive Non-Hodgkin's Lymphoma

Primary Outcome Measure:

  • Objective response rate (ORR)

Secondary Outcome Measures:

  • Complete response rate (CRR), disease control rate (DCR), progression-free survival (PFS), duration of response (DOR), overall survival (OS)
  • Safety and tolerability of copanlisib

Selected Inclusion Criteria:

  • Patients ≥18 years, with histologically confirmed MCL
  • Prior treatment with ibrutinib, including:
    • Completion of ≥1 cycle of ibrutinib treatment and confirmed evidence of disease progression or refractoriness to treatment
    • Discontinuation of ibrutinib treatment due to toxicity
  • Availability of fresh tumor tissue at screening
  • ECOG (Eastern Cooperative Oncology Group) performance status of ≤2
  • Adequate bone marrow, liver and renal function

Selected Exclusion Criteria:

  • Current central nervous system (CNS) involvement by lymphoma
  • New York Heart Association (NYHA) class III or IV heart disease
  • Unstable or new onset (within the last 3 months) angina
  • Myocardial infarction <6 months before start of study treatment
  • Uncontrolled arterial hypertension despite optimal medical management
  • Type I or II diabetes mellitus with HbA1c >8.5% or fasting plasma glucose >160 mg/dL at screening

For complete information please visit: http://www.clinicaltrials.gov (NCT02455297)

B-Cell Non-Hodgkin’s Lymphoma (NHL)

  • NHL is a diverse group of hematologic cancers composed of several subtypes characterized by the cell of origin1,2
  • 85% of NHL is of B-cell origin
  • Aggressive
  • Indolent
  • Denote B-cell differentiation steps
  • Assign lymphomas to their proposed normal counterpart

DLBCL=diffuse large B-cell lymphoma; FL=follicular lymphoma; MZL=marginal zone lymphoma (including MALT [mucosa-associated lymphoid tissue], nodal and splenic lymphomas); CLL=chronic lymphocytic leukemia/small lymphocytic lymphoma; MCL=mantle cell lymphoma; WM/LPL=Waldenström’s macroglobulinemia/lymphoplasmacytic lymphoma.

Adapted from Kuppers R et al. Nat Rev Can. 2005;5:251-260.3

PI3K Signaling Pathways in B-Cell Malignancies

  • The phosphatidylinositol-3-kinase (PI3K) pathway is one of the two most frequently activated pathways in human cancer.4 This pathway has been shown to play key roles in cell survival, proliferation, and differentation5
  • PI3K is activated downstream of the BCR, as well as many other receptors found on B-cells such as chemokine receptors and TLRs6
  • There are 4 distinct catalytic isoforms of PI3K which have overlapping functions.6 PI3K class I isoforms include PI3K-alpha (α), -beta (β), -gamma (γ) and -delta (δ)5
  • PI3K-delta serves as a central player for signaling from the BCR, which is known to promote malignant B-cell proliferation and survival6-8
  • In some B-cell malignancies, expression of certain PI3K isoforms, especially the PI3K-alpha isoform, is increased upon relapse and may contribute to tumor escape mechanisms6,9,10
Click or tap on the pathway elements below
to learn more about their role in NHL

Copanlisib: Mechanism of Action

Copanlisib is a pan class-I PI3K inhibitor with predominant activity against the alpha and delta isoforms

  • Copanlisib (formerly known as BAY 80-6946) is an investigational compound undergoing Phase III clinical trials for the treatment of patients with relapsed/refractory B-cell non-Hodgkin’s lymphoma (NHL). Copanlisib is not approved by the US FDA, EMA or other health authorities.
  • Copanlisib is a reversible pan class I PI3K inhibitor with preferential activity against both p110-α and p110-δ isoforms, compared with p110-beta (β) and p110-gamma (γ).18
  • Copanlisib inhibits the catalytic activity of the class I PI3K-α, -β, -γ, and -δ isoforms with IC50 values of 0.5, 3.7, 6.4, and 0.7 nmol/L, respectively.18

Adapted from: Liu N et al. 2013. Mol Cancer Ther; 12:2319-2330

References:

1. American Cancer Society. Non-Hodgkin lymphoma. Atlanta: American Cancer Society; 2014. 2. The Non-Hodgkin's Lymphoma Classification Project. Blood.
1997;89(11):3909-3918. 3. Küppers A. Nat Rev Cancer. 2005;5:251-262. 4. Liu N, et al. Poster presented at the 103rd AACR Annual Meeting, March 31-April 4 2012, Chicago,
Illinois, Poster 2799. 5. Liu P, et al. Nat Rev Drug Discov. 2009;8(8):627-644. 6. Brana I, Siu LL. BMC Med. 2012;10:161. 7. Lannutti BJ, Meadows SA, Herman SE et al. Blood.
2011;117:591–594. 8. Tzenaki N, Papakonstanti EA. Front Oncol. 2013;3:40. 9. Iyengar S, Clear A, Bodor C et al. Blood. 2013;121:2274–2284. 10. Psyrri A, Papageorgiou S,
Liakata E et al. Clin Cancer Res 2009;15:5724–5732. 11. Tabe Y, Jin L, Konopleva M et al. Acta Haematol. 2014;131:59–69. 12. Fruman DA, Cantley LC. N Engl J Med.
2014;370(11):1061-1062. 13. Rommel C, Camps M, Ji H. Nat Rev Immunol. 2007;7(3):191-201. 14. Vanhaesbroeck B, Guillermet-Guibert J, Graupera M, Bilanges B. Nat Rev Mol
Cell Biol
. 2010;11:329·341. 15. Arita A, McFarland DC, Myklebust JH, et al. Future Oncol. 2013;9(10):1549-1571. 16. Sorensen R, Meadows S, Yahiaoui A et al. Presented at:
American Society of Hematology Annual Meeting; December 5-8, 2015; Orlando, Florida: Abstract 2482. 17. Fang X, Zhou X, Wang X. Biomarker Res. 2013;1:30. 18. Liu N, et al.
Mol Cancer Ther. 2013;12:2319-30.