NCT02391116

Phase II Copanlisib in Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL)

Completed Phase 2 Results posted Last updated 4 January 2019

What this trial tests

Phase 2 trial testing Copanlisib (Aliqopa, BAY80-6946) in Diffuse, Large B-Cell, Lymphoma in 67 participants. Completed in 19 January 2018.

Timeline

8 May 2015

Primary endpoint
5 July 2016

19 January 2018

Quick facts

Lead sponsor	Bayer
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	67
Start date	8 May 2015
Primary completion	5 July 2016
Estimated completion	19 January 2018
Sites	32 locations across Denmark, France, Italy, Belgium, United Kingdom, Germany, South Korea, Canada

Drugs / interventions tested

• Copanlisib (Aliqopa, BAY80-6946) — full drug profile →

Conditions studied

• Diffuse, Large B-Cell, Lymphoma — all drugs for Diffuse, Large B-Cell, Lymphoma →

Sponsor

Bayer — full company profile →

Who can join

18 and older, any sex, with Diffuse, Large B-Cell, Lymphoma. 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) in Total Population Based on Investigator Assessment Primary · From start of study treatment assessed up to 24 weeks after the last participant fully evaluable for the primary endpoint started treatment (about 12 months)

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.

Full analysis set (FAS)

Group	Value	95% CI
Copanlisib (Aliqopa, BAY80-6946)	19.4	11.9 – 29.1

Per protocol set (PPS)

Group	Value	95% CI
Copanlisib (Aliqopa, BAY80-6946)	25.0	14.2 – 38.7

ORR by CD79b Status Based on Investigator Assessment Primary · From start of study treatment assessed up to 24 weeks after the last participant fully evaluable for the primary endpoint started treatment (about 12 months)

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.

Full analysis set (FAS)

Group	Value	95% CI
CD79b Mutant	22.2	4.1 – 55.0
CD79b Wild-type	20.0	10.9 – 32.3
CD79b Status Missing	15.4	2.8 – 41.0

Per protocol set (PPS)

Group	Value	95% CI
CD79b Mutant	25.0	4.6 – 60.0
CD79b Wild-type	25.0	13.1 – 40.6

ORR by DLBCL/COO Subtype Based on Investigator Assessment Primary · From start of study treatment assessed up to 24 weeks after the last participant fully evaluable for the primary endpoint started treatment (about 12 months)

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.

Full analysis set (FAS)

Group	Value	95% CI
Activated B-cell-like (ABC)	31.6	14.7 – 53.0
Germinal Center B-cell-like (GCB)	13.3	4.7 – 28.0
Unclassifiable	33.3	1.7 – 86.5
DLBCL/COO Subtype Missing	13.3	2.4 – 36.3

Per protocol set (PPS)

Group	Value	95% CI
Activated B-cell-like (ABC)	37.5	17.8 – 60.9
Germinal Center B-cell-like (GCB)	13.6	3.8 – 31.6
Unclassifiable	50.0	2.5 – 97.5

Duration of Response (DOR) in Total Population Secondary · From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first

The duration of response (DOR) was defined as the time from the date of first observed overall response (CR or PR) until radiological PD or death due to any cause, whichever was earlier. DOR was defined for responders only (i.e. participants with a best response of CR or PR), based on the investigator assessment of tumor response according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.

Group	Value	95% CI
Copanlisib (Aliqopa, BAY80-6946)	132	57 – 345

DOR by CD79b Status Secondary · From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first

The duration of response (DOR) was defined as the time from the date of first observed overall response (CR or PR) until radiological PD or death due to any cause, whichever was earlier. DOR was defined for responders only (i.e. participants with a best response of CR or PR), based on the investigator assessment of tumor response according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.

Group	Value	95% CI
CD79b Mutant	516	417 – 615
CD79b Wild-type	113	39 – 272
CD79b Status Missing	113	93 – 132

DOR by DLBCL/COO Subtype Secondary · From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first

The duration of response (DOR) was defined as the time from the date of first observed overall response (CR or PR) until radiological PD or death due to any cause, whichever was earlier. DOR was defined for responders only (i.e. participants with a best response of CR or PR), based on the investigator assessment of tumor response according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.

Group	Value	95% CI
Activated B-cell-like (ABC)	193	39 – 417
Germinal Center B-cell-like (GCB)	183	63 – 615
Unclassifiable	52	NA – NA
DLBCL/COO Subtype Missing	113	93 – 132

Progression-free Survival (PFS) in Total Population Secondary · From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first

The progression-free survival (PFS) was defined as the time from date of start of study treatment to radiological PD or death due to any cause, whichever was earlier, based on the investigator assessment of tumor response according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.

Group	Value	95% CI
Copanlisib (Aliqopa, BAY80-6946)	54	50 – 84

PFS by CD79b Status Secondary · From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first

The progression-free survival (PFS) was defined as the time from date of start of study treatment to radiological PD or death due to any cause, whichever was earlier, based on the investigator assessment of tumor response according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.

Group	Value	95% CI
CD79b Mutant	73	43 – 465
CD79b Wild-type	52	46 – 88
CD79b Status Missing	56	46 – 138

PFS by DLBCL/COO Subtype Secondary · From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first

The progression-free survival (PFS) was defined as the time from date of start of study treatment to radiological PD or death due to any cause, whichever was earlier, based on the investigator assessment of tumor response according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.

Group	Value	95% CI
Activated B-cell-like (ABC)	73	44 – 101
Germinal Center B-cell-like (GCB)	52	46 – 116
Unclassifiable	84	26 – 164
DLBCL/COO Subtype Missing	51	33 – 58

Overall Survival (OS) in Total Population Secondary · From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first

The overall survival (OS) was defined as the time from date of start of study treatment until death from any cause.

Group	Value	95% CI
Copanlisib (Aliqopa, BAY80-6946)	224	104 – 327

OS by CD79b Status Secondary · From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first

The overall survival (OS) was defined as the time from date of start of study treatment until death from any cause.

Group	Value	95% CI
CD79b Mutant	178	57 – NA
CD79b Wild-type	242	73 – 385
CD79b Status Missing	224	56 – 388

OS by DLBCL/COO Subtype Secondary · From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first

The overall survival (OS) was defined as the time from date of start of study treatment until death from any cause.

Group	Value	95% CI
Activated B-cell-like (ABC)	210	63 – 421
Germinal Center B-cell-like (GCB)	287	94 – 436
Unclassifiable	164	93 – 273
DLBCL/COO Subtype Missing	160	46 – 400

Adverse events — posted to ClinicalTrials.gov

Time frame: From start of test drug to 30 days after the last test drug intake, assessed up to 2 years after the last participant's first treatment or the last participant dies (whichever occurs first), with an average of 15 weeks for individual participant. Reporting threshold: 4%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Copanlisib (Aliqopa, BAY80-6946)

Serious: 44/67 (66%)

Deaths: 53/67

Serious adverse events (53 terms)

Reaction	System	Copanlisib (Aliqopa, BAY80…
General physical health deterioration	General disorders	—
Hyperglycaemia	Metabolism and nutrition disorders	—
Pyrexia	General disorders	—
Abdominal pain	Gastrointestinal disorders	—
Pneumonitis	Respiratory, thoracic and mediastinal disorders	—
Death	General disorders	—
Lung infection	Infections and infestations	—
Back pain	Musculoskeletal and connective tissue disorders	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—
Febrile neutropenia	Blood and lymphatic system disorders	—
Lymphadenopathy	Blood and lymphatic system disorders	—
Thrombocytopenia	Blood and lymphatic system disorders	—
Diplopia	Eye disorders	—
Colitis	Gastrointestinal disorders	—
Gastrointestinal haemorrhage	Gastrointestinal disorders	—
Nausea	Gastrointestinal disorders	—
Vomiting	Gastrointestinal disorders	—
Asthenia	General disorders	—
Fatigue	General disorders	—
Sudden death	General disorders	—
Cystitis	Infections and infestations	—
Herpes zoster	Infections and infestations	—
Lower respiratory tract infection	Infections and infestations	—
Pneumonia pneumococcal	Infections and infestations	—

Other adverse events (49 terms — click to expand)

Reaction	System	Copanlisib (Aliqopa, BAY80…
Hypertension	Vascular disorders	—
Diarrhoea	Gastrointestinal disorders	—
Hyperglycaemia	Metabolism and nutrition disorders	—
Nausea	Gastrointestinal disorders	—
Fatigue	General disorders	—
Vomiting	Gastrointestinal disorders	—
Pyrexia	General disorders	—
Cough	Respiratory, thoracic and mediastinal disorders	—
Constipation	Gastrointestinal disorders	—
Decreased appetite	Metabolism and nutrition disorders	—
Neutropenia	Blood and lymphatic system disorders	—
Headache	Nervous system disorders	—
Rash	Skin and subcutaneous tissue disorders	—
Mouth ulceration	Gastrointestinal disorders	—
Hypokalaemia	Metabolism and nutrition disorders	—
Oedema peripheral	General disorders	—
Anaemia	Blood and lymphatic system disorders	—
Thrombocytopenia	Blood and lymphatic system disorders	—
Muscle spasms	Musculoskeletal and connective tissue disorders	—
Dry skin	Skin and subcutaneous tissue disorders	—
Abdominal pain	Gastrointestinal disorders	—
Stomatitis	Gastrointestinal disorders	—
Platelet count decreased	Investigations	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—
Mucosal inflammation	General disorders	—
Upper respiratory tract infection	Infections and infestations	—
Hyponatraemia	Metabolism and nutrition disorders	—
Arthralgia	Musculoskeletal and connective tissue disorders	—
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Dizziness	Nervous system disorders	—
Paraesthesia	Nervous system disorders	—
Productive cough	Respiratory, thoracic and mediastinal disorders	—
Tachycardia	Cardiac disorders	—
Paraesthesia oral	Gastrointestinal disorders	—
Asthenia	General disorders	—
Chest pain	General disorders	—
Chills	General disorders	—
Fall	Injury, poisoning and procedural complications	—
Lipase increased	Investigations	—
Lymphocyte count decreased	Investigations	—

Most-reported serious reactions: General physical health deterioration, Hyperglycaemia, Pyrexia, Abdominal pain, Pneumonitis, Death, Lung infection, Back pain.

Data from ClinicalTrials.gov NCT02391116 adverse events section.

Sponsor's own description

To assess the potential efficacy (in terms of objective response) of single agent copanlisib in patients with relapsed or refractory Diffuse large B-cell lymphoma (DLBCL) and assess the relationship between efficacy and a potentially predictive biomarker

Publications & conference data

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

1. 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
2. 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
3. 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
4. Receptor tyrosine kinases and downstream pathways as druggable targets for cancer treatment: the current arsenal of inhibitors.
   Montor WR, Salas AROSE, Melo FHM. · · 2018 · cited 80× · PMID 29455659 · DOI 10.1186/s12943-018-0792-2
5. Development and safety of PI3K inhibitors in cancer.
   Yu M, Chen J, Xu Z, Yang B, et al · · 2023 · cited 71× · PMID 36773078 · DOI 10.1007/s00204-023-03440-4
6. PI3Kδ-selective and PI3Kα/δ-combinatorial inhibitors in clinical development for B-cell non-Hodgkin lymphoma.
   Lampson BL, Brown JR. · · 2017 · cited 61× · PMID 28945111 · DOI 10.1080/13543784.2017.1384815
7. Single-agent activity of phosphatidylinositol 3-kinase inhibition with copanlisib in patients with molecularly defined relapsed or refractory diffuse large B-cell lymphoma.
   Lenz G, Hawkes E, Verhoef G, Haioun C, et al · · 2020 · cited 53× · PMID 32060403 · DOI 10.1038/s41375-020-0743-y
8. Copanlisib for treatment of B-cell malignancies: the development of a PI3K inhibitor with considerable differences to idelalisib.
   Krause G, Hassenrück F, Hallek M. · · 2018 · cited 51× · PMID 30174412 · DOI 10.2147/dddt.s142406