Copanlisib and Rituximab in Relapsed Indolent B-cell Non-Hodgkin's Lymphoma (iNHL) (CHRONOS-3)

A Phase III, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Copanlisib in Combination With Rituximab in Patients With Relapsed Indolent B-cell Non-Hodgkin's Lymphoma (iNHL) - CHRONOS-3

The purpose of this study was to evaluate whether copanlisib in combination with rituximab is superior to placebo in combination with rituximab in prolonging progression free survival (PFS) in patients with relapsed iNHL who have received one or more lines of treatment, including rituximab and who either had a treatment-free interval of ≥ 12 months after completion of the last rituximab-containing treatment, or who are unwilling to receive chemotherapy/for whom chemotherapy is contraindicated on reason of age, comorbidities, and/or residual toxicity.

Study Overview

• Status: Completed
• Conditions: Lymphoma,Non-Hodgkin
• Intervention / Treatment: Drug: Copanlisib (Aliqopa, BAY80-6946); Drug: Rituximab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 458
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Córdoba, Argentina, X5000AOQ
  • Ciudad Auton. de Buenos Aires
    • Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, TBC
  • Santa Fe Province
    • Rosario, Santa Fe Province, Argentina, S2000DEJ
  • Tucumán Province
    • San Miguel de Tucumán, Tucumán Province, Argentina, T4000
• Australia
  • Nedlands, Australia, 6009
  • Victoria
    • Ballarat, Victoria, Australia, 3350
• Austria
  • Vienna, Austria, 1090
  • Vienna, Austria, 1130
  • Styria
    • Graz, Styria, Austria, 8036
• Belgium
  • Ottignies, Belgium, 1340
• Brazil
  • São Paulo, Brazil, 05403-000
  • São Paulo, Brazil, 05651-901
  • Rio Grande do Sul
    • Passo Fundo, Rio Grande do Sul, Brazil, 99020-240
    • Porto Alegre, Rio Grande do Sul, Brazil, 90850-170
  • São Paulo
    • Barretos/SP, São Paulo, Brazil, 14784-400
    • Jaú, São Paulo, Brazil, 17210-120
    • São Paulo, São Paulo, Brazil, 01234-030
    • São Paulo, São Paulo, Brazil, 08270-070
• Bulgaria
  • Plovdiv, Bulgaria, 4000
  • Sofia, Bulgaria, 1756
  • Varna, Bulgaria, 9010
• Chile
  • Región de la Araucanía
    • Temuco, Región de la Araucanía, Chile, 4800827
• China
  • Beijing, China, 100050
  • Beijing, China, 100730
  • Beijing, China, 100083
  • Beijing, China, 100000
  • Chongqing, China, 400042
  • Chongqing, China, 400030
  • Shanghai, China, 200032
  • Shanghai, China, 200025
  • Shanghai, China, 200000
  • Tianjin, China, 300000
  • Tianjin, China, 300121
  • Fujian
    • Fuzhou, Fujian, China, 350000
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
    • Guangzhou, Guangdong, China, TBC
  • Hubei
    • Wuhan, Hubei, China, 430079
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
    • Suzhou, Jiangsu, China, 215000
  • Jiangxi
    • Nanchang, Jiangxi, China, 330029
  • Jilin
    • Changchun, Jilin, China, 130061
  • Liaoning
    • Shengyang, Liaoning, China, 110042
  • Sichuan
    • Chengdu, Sichuan, China, 610041
  • Xinjiang
    • Ürümqi, Xinjiang, China, 830011
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
    • Hangzhou, Zhejiang, China, 310022
• Colombia
  • Antioquia
    • Medellín, Antioquia, Colombia, 050034
  • Cundinamarca
    • Bogota, Cundinamarca, Colombia, 111511
  • Departamento de Córdoba
    • Montería, Departamento de Córdoba, Colombia, 230002
  • Valle del Cauca Department
    • Santiago de Cali, Valle del Cauca Department, Colombia, 760032
• France
  • Bayonne, France, 64100
  • Brest, France, 29470
  • Metz, France, 57085
  • Nice, France, 6189
  • Pessac, France, 33600
  • Poitiers, France, 86021
  • Saint-Herblain, France, 44800
• Germany
  • Berlin, Germany, 10967
  • Bavaria
    • München, Bavaria, Germany, 81377
  • North Rhine-Westphalia
    • Recklinghausen, North Rhine-Westphalia, Germany, 45659
  • Saxony
    • Dresden, Saxony, Germany, 1307
  • Saxony-Anhalt
    • Halle, Saxony-Anhalt, Germany, 6120
• Greece
  • Athens, Greece, 11527
  • Athens, Greece, 106 76
  • Chaïdári, Greece, 12462
  • Pátrai, Greece, 26500
• Hong Kong
  • Chai Wan, Hong Kong
  • Hong Kong, Hong Kong, MISSING
• Hungary
  • Budapest, Hungary, 1083
  • Győr, Hungary, 9024
  • Kaposvár, Hungary, 7400
  • Pécs, Hungary, 7623
  • Tatabánya, Hungary, 2800
• Ireland
  • Dublin, Ireland, D07R2WY
  • Dublin, Ireland, D08NHY1
  • Galway, Ireland, H91YR71
• Italy
  • Friuli Venezia Giulia
    • Udine, Friuli Venezia Giulia, Italy, 33038
  • Liguria
    • Genoa, Liguria, Italy, 16132
  • Lombardy
    • Milan, Lombardy, Italy, 20133
  • Tuscany
    • Florence, Tuscany, Italy, 50134
• Japan
  • Aomori, Japan, 030-8553
  • Fukuoka, Japan, 811-1395
  • Kumamoto, Japan, 860-8556
  • Niigata, Japan, 951-8566
  • Osaka, Japan, 545-8586
  • Yamagata, Japan, 990-9585
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 464-8681
    • Nagoya, Aichi-ken, Japan, 466-8650
  • Gunma
    • Maebashi, Gunma, Japan, 371-8511
  • Hyōgo
    • Kobe, Hyōgo, Japan, 650-0047
  • Kochi
    • Nankoku, Kochi, Japan, 783-8505
  • Miyagi
    • Sendai, Miyagi, Japan, 980-8574
  • Nagasaki
    • Ōmura, Nagasaki, Japan, 856-8562
  • Okayama-ken
    • Kurashiki, Okayama-ken, Japan, 710-8602
  • Osaka
    • Hirakata, Osaka, Japan, 573-1191
  • Shimane
    • Izumo, Shimane, Japan, 693-8501
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
• Lithuania
  • Kaunas, Lithuania, LT-50009
• Malaysia
  • Cheras, Malaysia, 56000
  • Kota Kinabalu, Malaysia, 88586
  • Kuala Lumpur, Malaysia, 59100
  • Kuala Selangor, Malaysia, 68000
  • Perak, Malaysia, 30450
  • Pulau Pinang, Malaysia, 10450
• Mexico
  • Michoacán
    • Morelia, Michoacán, Mexico, 58260
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
• New Zealand
  • Tauranga, New Zealand, 3112
• Philippines
  • City of Taguig, Philippines, 1102
  • Pasig, Philippines, 1605
• Poland
  • Gdansk, Poland, 80-214
  • Gdynia, Poland, 81-519
  • Krakow, Poland, 30-727
  • Lublin, Poland, 20-090
• Portugal
  • Porto, Portugal, 4200-072
  • Porto, Portugal, 4434-502
• Romania
  • Brasov, Romania, 500152
  • Bucharest, Romania, 10825
  • Bucharest, Romania, 22328
  • Bucharest, Romania, 20125
  • Bucharest, Romania, 30171
  • Cluj-Napoca, Romania, 400015
  • Craiova, Romania, 200143
  • Târgu Mureş, Romania, 540136
• Russia
  • Chelyabinsk, Russia, 454048
  • Irkutsk, Russia, 664035
  • Kazan', Russia, 420029
  • Kemerovo, Russia, 650066
  • Kirov, Russia, 610027
  • Novosibirsk, Russia, 630087
  • Omsk, Russia, 644013
  • Saint Petersburg, Russia, 197022
  • Volgograd, Russia, 400138
• Singapore
  • Singapore, Singapore, 169608
  • Singapore, Singapore, 119074
  • Singapore, Singapore, 168583
• Slovakia
  • Poprad, Slovakia, 058 01
• South Africa
  • Eastern Cape
    • George, Eastern Cape, South Africa, 6530
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2013
• South Korea
  • Busan, South Korea, 49201
  • Busan, South Korea, 49241
  • Hwasun Gun, South Korea, 58128
  • Seoul, South Korea, 06351
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, South Korea, 03722
    • Seoul, Seoul Teugbyeolsi, South Korea, 05505
    • Seoul, Seoul Teugbyeolsi, South Korea, 3080
• Spain
  • Barcelona, Spain, 08003
  • Barcelona, Spain, 08035
  • Barcelona, Spain, 8041
  • Madrid, Spain, 28041
  • Salamanca, Spain, 37007
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
  • Málaga
    • Málaga, Málaga, Spain, 20910
• Taiwan
  • Changhua, Taiwan, 50006
  • Kaohsiung City, Taiwan, 833
  • Tainan City, Taiwan, 704
  • Taipei, Taiwan, 100
  • Taipei, Taiwan, 11217
• Thailand
  • Chiang Mai, Thailand, 50200
  • Pathum Thani, Thailand, 10120
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 6100
  • Istanbul, Turkey (Türkiye), 34093
  • Izmir, Turkey (Türkiye), 35100
  • Kayseri, Turkey (Türkiye), 38039
  • Trabzon, Turkey (Türkiye), 61080
• Ukraine
  • Cherkasy, Ukraine, 18009
  • Dnipro, Ukraine, 49102
  • Kyiv, Ukraine, 03022
  • Lviv, Ukraine, 79044
  • Vinnitsa, Ukraine, 21029
• United States
  • California
    • West Covina, California, United States, 91790
  • Kentucky
    • Ashland, Kentucky, United States, 41101
    • Louisville, Kentucky, United States, 40207
  • Maryland
    • Bethesda, Maryland, United States, 20817
  • Nevada
    • Las Vegas, Nevada, United States, 89169
  • New Jersey
    • Montvale, New Jersey, United States, 07645
    • New Jersey, New Jersey, United States
      • MSK Basking Ridge
    • New Jersey, New Jersey, United States
      • MSK Bergen
    • New Jersey, New Jersey, United States
      • MSK Monmoth
  • New York
    • Harrison, New York, United States
      • MSK Westchester
    • Long Island City, New York, United States
      • MSK Commack
    • Long Island City, New York, United States
      • MSK Rockville Centre
    • New York, New York, United States, 10065
  • Ohio
    • Canton, Ohio, United States, 44718
  • Utah
    • Salt Lake City, Utah, United States, 84106
  • Washington
    • Spokane, Washington, United States, 99208
• Vietnam
  • Ho Chi Minh City, Vietnam, 70000
  • Hà Nội, Vietnam, 10000

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed diagnosis of Indolent non-Hodgkin's lymphoma (iNHL) in CD20 positive patients, with histological subtype limited to:

  • Follicular lymphoma(FL) grade1-2-3a
  • Small lymphocytic lymphoma(SLL) with absolute lymphocyte count <5x10*9/L at study entry
  • Lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM)
  • Marginal zone lymphoma (MZL) (splenic, nodal, or extra-nodal)
• Patients must have relapsed (recurrence after complete response or presented progression after partial response) after the last rituximab-, rituximab biosimilars-, or anti-CD20 monoclonal antibody (e.g. obinutuzumab)-containing therapy (other previous treatment lines after rituximab are allowed). A previous regimen is defined as one of the following: at least 2 months of single-agent therapy (less than 2 months of therapy is allowed for patients who responded to single-agent rituximab, rituximab biosimilars, or anti-CD20 monoclonal antibody); at least 2 consecutive cycles of polychemotherapy; autologous transplant; radioimmunotherapy. Previous exposure to PI3K is acceptable (except to copanlisib) provided there is no resistance. Patients with prior intolerance to PI3K inhibitors other than copanlisib are eligible.
• Non-WM must have at least one bi-dimensionally measurable lesion (which has not been previously irradiated) according to the Lugano Classification. For patients with splenic MZL (Marginal-zone lymphoma) this requirement may be restricted to splenomegaly alone since that is usually the only manifestation of measurable disease.
• Patients affected by WM who do not have at least one bi-dimensionally measurable lesion in the baseline radiologic assessment must have measurable disease, defined as presence of immunoglobulin M (IgM) paraprotein with a minimum IgM level ≥ 2 x upper limit of normal (ULN) and positive immunofixation test .
• Male or female patients ≥ 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Life expectancy of at least 3 months
• Availability of fresh tumor tissue and/or archival tumor tissue for central pathology(obtained within 5 years of the consent date) at Screening
• Adequate baseline laboratory values collected no more than 7 days before starting study treatment
• Left ventricular ejection fraction ≥ 45%

• Patients must either:

  • have had a progression-free and treatment-free interval of at least 12 months after completion of the rituximab-, rituximab biosimilars-, or anti-CD20 monoclonal antibody-containing treatment OR

  • be considered unfit to receive chemotherapy on reason of age, concomitant morbidities, and/or residual toxicity from previous treatments, or unwillingness to receive chemotherapy. These patients must also have had a progression-free and treatment-free interval of at least 6 months after completion of the last rituximab-, rituximab biosimilars-, or anti-CD20 monoclonal antibody-containing treatment. Patients in whom chemotherapy is contraindicated are defined by one of the following features:

    • Age ≥ 80 years

    • Age < 80 years and at least 1 of the following conditions:

      • at least 3 grade 3 CIRS-G comorbidities OR
      • at least 1 grade 4 CIRS-G comorbidity (if compatible to participation in the study).

Exclusion Criteria:

• Histologically confirmed diagnosis of follicular lymphoma grade 3b or transformed disease, or chronic lymphocytic leukemia
• Progression free interval or treatment free interval of less than 12 months since the last rituximab-, rituximab biosimilars-, or anti-CD20 monoclonal antibody (e.g. obinutuzumab)-containing treatment(including maintenance with these drugs). For patients considered unwilling/unfit to receive chemotherapy : progression free interval or treatment free interval of less than 6 months since the last rituximab-, rituximab biosimilars-, or anti-CD20 monoclonal antibody-containing treatment (including maintenance with these drugs), as assessed by the investigator
• History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function
• Known lymphomatous involvement of the central nervous system
• Patients with HbA1c > 8.5% at Screening
• Known history of human immunodeficiency virus (HIV) infection
• Hepatitis B (HBV) or hepatitis C (HCV). Patients positive for HBsAg or HBcAb will be eligible if they are negative for HBV-DNA, these patients should receive prophylactic antiviral therapy. Patients positive for anti- HCV antibody will be eligible if they are negative for HCV-RNA
• Documented evidence of resistance to prior treatment with idelalisib or other PI3K inhibitors.
• Prior treatment with copanlisib
• Cytomegalovirus (CMV) infection. Patients who are CMV PCR positive at baseline will not be eligible.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Copanlisib + Rituximab; Combination of the Copanlisib and rituximab	Drug: Copanlisib (Aliqopa, BAY80-6946); 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.; Drug: Rituximab; 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.
Placebo Comparator: Placebo + Rituximab; Combination of Copanlisib placebo and rituximab	Drug: Rituximab; 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.; Drug: Placebo; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) Based on Independent Central Review.	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).	From first participant randomization (20-Aug-2015) up to data cut-off at primary completion (31-Aug-2020), approximately 5 years and 2-year follow-up after primary completion at 31-Aug-2022, up to 7 years and final analysis at 15-Nov-2024 up to 9 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Objective response rate (ORR) was defined as the percentage of participants who have a best response rating over the whole duration of the study (i.e. until time of analysis of PFS) of complete response (CR) or partial response (PR) according to the Lugano Classification and for patients with Waldenström macroglobulinemia (WM) a response rating of CR, very good partial response (VGPR), PR, or minor response (MR) according to the Owen Criteria (kindly refer to the links in the Protocol section).	From first participant randomization (20-Aug-2015) up to data cut-off date at primary completion (31-Aug-2020), approximately 5 years and 2-year follow-up after primary completion at 31-Aug-2022, up to 7 years
Complete Response Rate (CRR)	Complete response rate (CRR) was defined as the percentage of participants who had a best response rating over the whole duration of the study (i.e., until the time of analysis of PFS) according to the Lugano Classification and for patients with Waldenström macroglobulinemia (WM) a response rating of Complete Response according to the Owen Criteria (kindly refer to the links in the Protocol section).	From first participant randomization (20-Aug-2015) up to data cut-off date at primary completion (31-Aug-2020), approximately 5 years and 2-year follow-up after primary completion at 31-Aug-2022, up to 7 years
Duration of Response (DOR)	Duration of response (DOR) was defined as the time (in days) from first observed tumor response Complete Response (CR), Very good partial response (VGPR), Partial Response (PR) or Minor Response (MR) until progression or death from any cause, whichever occurred earlier according to the Owen Criteria (kindly refer to the links in the Protocol section). Only patients with response in FAS were included in the analysis.	From first participant randomization (20-Aug-2015) up to data cut-off date at primary completion (31-Aug-2020), approximately 5 years and 2-year follow-up after primary completion at 31-Aug-2022, up to 7 years
Disease Control Rate (DCR)	Disease control rate was defined as the percentage of participants who had a best response rating as Complete Response (CR), Partial Response (PR) or stable disease (SD) according to the Lugano Classification and for patients with Waldenström macroglobulinemia (WM) as a response rating of CR, very good partial response (VGPR), PR, minor response (MR) or stable disease (SD) according to the Owen Criteria (kindly refer to the links in the Protocol section).	From first participant randomization (20-Aug-2015) up to data cut-off date at primary completion (31-Aug-2020), approximately 5 years and 2-year follow-up after primary completion at 31-Aug-2022, up to 7 years
Time to Progression (TTP)	Time to progression (TTP) was defined as the time (days) from date of randomization to date of first observed disease progression according to the Lugano Classification and Response criteria in patients affected by Waldenström macroglobulinemia (kindly refer to the links in the Protocol section).	From first participant randomization (20-Aug-2015) up to data cut-off date at primary completion (31-Aug-2020), approximately 5 years and 2-year follow-up after primary completion at 31-Aug-2022, up to 7 years
Time to Deterioration in DRS-P (Disease-Related Symptoms - Physical) of at Least Three Points, as Measured by the Functional Assessment of Cancer Therapy Lymphoma Symptom Index-18 (FLymSI-18) Questionnaire.	Time to deterioration in DRS-P (Disease-Related Symptoms - Physical) of at least three points was defined as the time (in days) from randomization to DRS-P decline, progression, or death due to any reason, whichever occurred earlier. The Lymphoma Symptom Index-18 (FLymSI-18) questionnaire contains 18 items, each of which utilizes a Likert scale with 5 possible responses ranging from 0 'Not at all' to 4 'Very much' and was divided into a total score.	From first participant randomization (20-Aug-2015) up to data cut-off date at primary completion (31-Aug-2020), approximately 5 years and 2-year follow-up after primary completion at 31-Aug-2022, up to 7 years
Time to Improvement in DRS-P (Disease-Related Symptoms - Physical) of at Least 3 Points, as Measured by the Functional Assessment of Cancer Therapy Lymphoma Symptom Index-18 (FLymSI-18) Questionnaire.	Time to improvement in DRS-P (Disease-Related Symptoms - Physical) was defined as the time (in days) from randomization to DRS-P improvement of at least three points. The Lymphoma Symptom Index-18 (FLymSI-18) questionnaire contains 18 items, each of which utilizes a Likert scale with 5 possible responses ranging from 0 'Not at all' to 4 'Very much' and was divided into a total score.	From first participant randomization (20-Aug-2015) up to data cut-off date at primary completion (31-Aug-2020), approximately 5 years and 2-year follow-up after primary completion at 31-Aug-2022, up to 7 years
Number of Participants With Treatment-emergent Adverse Events (TEAEs) at Primary Completion Date.	Adverse events were considered to be treatment-emergent if they have started or worsened after first application of study medication up to 30 days after end of treatment with study medication.	Up to 30 days after end of treatment with study drug, data reporting cut-off at 5 years from the first participant randomization date
Number of Participants With Treatment-emergent Adverse Events (TEAEs) at 2-year Follow-up Cut-off Date.	Adverse events were considered to be treatment-emergent if they have started or worsened after first application of study medication up to 30 days after end of treatment with study medication.	Up to 30 days after end of treatment with study drug, data reporting cut-off at 7 years from the first participant randomization date
Overall Survival (OS)	Overall survival was defined as the time (in days) from randomization until death from any cause.	From randomization up to the final analysis at 15-Nov-2024 up to 9 years
Number of Participants With Treatment-emergent Adverse Events (TEAEs) at Final Analysis	Adverse events were considered to be treatment-emergent if they have started or worsened after first application of study medication up to 30 days after end of treatment with study medication.	Up to 30 days after end of treatment with study drug, data reporting cut-off at final analysis, up to 9 years

Collaborators and Investigators

• Sponsor: Bayer
• Investigators: Study Director: Bayer Study Director, Bayer

Publications and helpful links

General Publications

• Matasar MJ, Capra M, Ozcan M, Lv F, Li W, Yanez E, Sapunarova K, Lin T, Jin J, Jurczak W, Hamed A, Wang MC, Baker R, Bondarenko I, Zhang Q, Feng J, Geissler K, Lazaroiu M, Saydam G, Szomor A, Bouabdallah K, Galiulin R, Uchida T, Soler LM, Cao A, Hiemeyer F, Mehra A, Childs BH, Shi Y, Zinzani PL. Copanlisib plus rituximab versus placebo plus rituximab in patients with relapsed indolent non-Hodgkin lymphoma (CHRONOS-3): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2021 May;22(5):678-689. doi: 10.1016/S1470-2045(21)00145-5. Epub 2021 Apr 10.
• Morcos PN, Moss J, Veasy J, Hiemeyer F, Childs BH, Garmann D. Model-Based Benefit/Risk Analysis for the Copanlisib Intermittent Dosing Regimen. Clin Pharmacol Ther. 2024 May;115(5):1092-1104. doi: 10.1002/cpt.3173. Epub 2024 Jan 16.

Helpful Links

• Click here to find information about studies related to Bayer AG products conducted in Europe.
• Click here to find further information and, after study completion, the study results according to Bayer's transparency standards

Study record dates

Study Major Dates

• Study Start (Actual): August 3, 2015
• Primary Completion (Actual): August 31, 2020
• Study Completion (Actual): November 15, 2024

Study Registration Dates

• First Submitted: February 12, 2015
• First Submitted That Met QC Criteria: February 13, 2015
• First Posted (Estimated): February 20, 2015

Study Record Updates

• Last Update Posted (Estimated): October 14, 2025
• Last Update Submitted That Met QC Criteria: September 25, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Non-Hodgkin's lymphoma; Clinical trial, Phase III; Phosphatidylinositol-3-kinase; Indolent B-cell non-Hodgkin's lymphoma
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, Non-Hodgkin; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Murine-Derived; Rituximab; copanlisib
• Other Study ID Numbers: 17067; 2013-003893-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No