NCT01685008

Study of Fc-Optimized Anti-CD19 Antibody (MOR00208) to Treat Non-Hodgkin's Lymphoma (NHL)

Completed Phase 2 Results posted Last updated 7 November 2023

What this trial tests

Phase 2 trial testing MOR00208 (formerly Xmab 5574) in Non-Hodgkin Lymphoma in 92 participants. Completed in 6 April 2022.

Timeline

23 April 2013

Primary endpoint
6 April 2022

6 April 2022

Quick facts

Lead sponsor	MorphoSys AG
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	92
Start date	23 April 2013
Primary completion	6 April 2022
Estimated completion	6 April 2022
Sites	22 locations across Italy, Belgium, Germany, Hungary, Poland, United States, Spain

Drugs / interventions tested

• MOR00208 (formerly Xmab 5574) — full drug profile →

Conditions studied

• Non-Hodgkin Lymphoma — all drugs for Non-Hodgkin Lymphoma →

Sponsor

MorphoSys AG — full company profile →

Who can join

18 and older, any sex, with Non-Hodgkin 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.

Overall Response Rate (ORR) Primary · From first dose until Follow-up Visit 12, up to 4.5 years

Proportion of patients with Complete Remission (CR; disappearance of all evidence of disease) or Partial Remission (PR; regression of measurable disease and no new sites), assessed as per the 2007 International Working Group (IWG) response criteria by radiographic evaluations (CT, PET, MRI, or other).

Complete remission

Group	Value	95% CI
Total	6
FL Subtype	2
DLBCL Subtype	2
MCL Subtype	0
Other iNHL	2
FL + Other iNHL	4

Partial remission

Group	Value	95% CI
Total	16
FL Subtype	8
DLBCL Subtype	7
MCL Subtype	0
Other iNHL	1
FL + Other iNHL	9

Stable Disease (SD) Rate Secondary · From first dose until Follow-up Visit 12, up to 4.5 years

Proportion of patients with Stable Disease (failure to attain CR/PR with no progressive disease)

Group	Value	95% CI
Total	31
FL Subtype	16
DLBCL Subtype	5
MCL Subtype	6
Other iNHL	4
FL + Other iNHL	20

Duration of Response (DoR) Secondary · From first dose until Follow-up Visit 12, up to 4.5 years

Time from first CR or PR to first documentation of relapse/progression (any new lesion or increase by ≥ 50% of previously identified site)

Group	Value	95% CI
Total	24.0	11.1 – NA
FL Subtype	24.0	2.6 – NA
DLBCL Subtype	20.1	1.1 – NA
Other iNHL	NA	NA – NA
FL + Other iNHL	NA	3.6 – NA

Time to Progression (TTP) Secondary · From first dose until Follow-up Visit 12, up to 4.5 years

Time from first dosing until documentation of progression or death due to lymphoma

Group	Value	95% CI
Total	5.4	3.4 – 12.0
FL Subtype	8.8	5.4 – 20.5
DLBCL Subtype	3.1	2.1 – 15.4
MCL Subtype	3.0	1.8 – NA
Other iNHL	NA	2.0 – NA
FL + Other iNHL	6.6	5.3 – 20.5

Progression-free Survival (PFS) Secondary · From first dose until Follow-up Visit 12, up to 4.5 years

Time from first dosing until progression or death due to any case

Group	Value	95% CI
Total	5.4	3.2 – 9.9
FL Subtype	8.8	5.4 – 20.5
DLBCL Subtype	2.7	2.1 – 13.2
MCL Subtype	2.1	1.7 – NA
Other iNHL	NA	2.0 – NA
FL + Other iNHL	6.6	5.3 – 20.5

Incidence and Severity of Adverse Events (AEs) Secondary · From first dose until 30 days after last dose of MOR00208, up to 8.5 years

Number of patients with treatment-emergent AEs rated Mild, Moderate, and Severe

Mild

Group	Value	95% CI
Total	29
FL Subtype	10
DLBCL Subtype	12
MCL Subtype	1
Other iNHL	6
FL + Other iNHL	16

Moderate

Group	Value	95% CI
Total	20
FL Subtype	8
DLBCL Subtype	8
MCL Subtype	2
Other iNHL	2
FL + Other iNHL	10

Severe

Group	Value	95% CI
Total	6
FL Subtype	2
DLBCL Subtype	4
MCL Subtype	0
Other iNHL	0
FL + Other iNHL	2

Number and Proportion of Patients Who Potentially Developed Anti-MOR00208 Antibodies and Semiquantitative Anti-MOR00208 Antibody Assessments Secondary · From first dose until Follow-up Visit 3, up to 7 months

Number of patients with at least one positive (+ve) post-Baseline sample containing positive anti-MOR00208 antibodies; Baseline (pre-dose) sample has to be tested negative (-ve)

Group	Value	95% CI
Total	0
FL Subtype	0
DLBCL Subtype	0
MCL Subtype	0
Other iNHL	0
FL + Other iNHL	0
Total	82
FL Subtype	31
DLBCL Subtype	31
MCL Subtype	10
Other iNHL	10
FL + Other iNHL	41
Total	0
FL Subtype	0
DLBCL Subtype	0
MCL Subtype	0
Other iNHL	0
FL + Other iNHL	0
Total	5
FL Subtype	3
DLBCL Subtype	1
MCL Subtype	1
Other iNHL	0
FL + Other iNHL	3

Pharmacokinetic (PK) Parameter: Maximum Serum Concentration Observed (Cmax) of MOR00208 Secondary · Estimated from first dose (samples taken on first day of dosing at pre-dose, end of infusion, after 1 hour, 4 hours, 24 hours, and pre-dose on Day 8)

The highest concentration of MOR00208 measured in serum

Group	Value	95% CI
Total	263.1	± 111.35
FL Subtype	276.6	± 73.10
DLBCL Subtype	253.4	± 157.79
MCL Subtype	260.0	± 69.85
Other iNHL	251.5	± 70.31
FL + Other iNHL	271.2	± 72.42

PK Parameter: Time to Maximum Serum Concentration Observed (Tmax) of MOR00208 Secondary · Estimated from first dose (samples taken on first day of dosing at pre-dose, end of infusion, after 1 hour, 4 hours, 24 hours, and pre-dose on Day 8)

The time to highest concentration of MOR00208 measured in serum

Group	Value	95% CI
Total	5.8	± 17.46
FL Subtype	4.7	± 5.27
DLBCL Subtype	8.5	± 27.99
MCL Subtype	3.0	± 1.03
Other iNHL	3.4	± 1.38
FL + Other iNHL	4.4	± 4.72

PK Parameter: Apparent Trough Serum Concentration Before Dosing (Clast) of MOR00208 Secondary · Estimated from first dose (samples taken on first day of dosing at pre-dose, end of infusion, after 1 hour, 4 hours, 24 hours, and pre-dose on Day 8)

The last quantifiable concentration from the first dose of MOR00208

Group	Value	95% CI
Total	81.0	± 36.66
FL Subtype	88.6	± 39.50
DLBCL Subtype	69.6	± 28.96
MCL Subtype	82.4	± 34.54
Other iNHL	92.2	± 47.23
FL + Other iNHL	89.3	± 40.69

PK Parameter: Area Under the Concentration Curve From Dose Time Zero to the Time the Last Quantifiable Concentration is Observed (AUC[0-t]) of MOR00208 Secondary · Estimated from first dose (samples taken on first day of dosing at pre-dose, end of infusion, after 1 hour, 4 hours, 24 hours, and pre-dose on Day 8)

Area under the concentration curve. The time curve from time zero (0) to the time that the last concentration above the lower limit of quantification (LLQ) is observed.

Group	Value	95% CI
Total	21942.5	± 11847.35
FL Subtype	25088.6	± 16245.82
DLBCL Subtype	19106.3	± 8170.03
MCL Subtype	21617.1	± 4577.21
Other iNHL	20888.5	± 7669.67
FL + Other iNHL	24188.6	± 14849.65

PK Parameter: Area Under the Concentration Curve From Dose Time Zero to Infinity (AUC[0-inf]) of MOR00208 Secondary · Estimated from final dose (samples collected on the last day of Cycle 3 [C3D28; each cycle is 28 days long], and Follow-up Visits 1 [C3D28 + 4 weeks], 2 [C3D28 + 10 weeks], and 3 [C3D28 + 16 weeks])

Area under the concentration curve. The time curve from time zero (0) to infinity (inf), where infinity is computed from AUC0-t + \[Ct/λZ)\]. Ct is calculated from the concentration at the last sampling time at which the sample is above LLQ.

Group	Value	95% CI
Total	NA	± NA
FL Subtype	NA	± NA
DLBCL Subtype	NA	± NA
MCL Subtype	NA	± NA
Other iNHL	NA	± NA
FL + Other iNHL	NA	± NA

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected from informed consent until 30 days after last dose of MOR00208, up to 8.5 years. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Total

Serious: 30/92 (33%)

Deaths: 9/92

FL Subtype

Serious: 7/34 (21%)

Deaths: 1/34

DLBCL Subtype

Serious: 18/35 (51%)

Deaths: 6/35

MCL Subtype

Serious: 2/12 (17%)

Deaths: 2/12

Other iNHL

Serious: 3/11 (27%)

Deaths: 0/11

FL + Other iNHL

Serious: 10/45 (22%)

Deaths: 1/45

Serious adverse events (23 terms)

Reaction	System	Total	FL Subtype	DLBCL Subtype	MCL Subtype	Other iNHL	FL + Other iNHL
Disease progression	General disorders	—	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—
Herpes zoster	Infections and infestations	—	—	—	—	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—	—	—	—	—
Cardiac failure	Cardiac disorders	—	—	—	—	—	—
Vision blurred	Eye disorders	—	—	—	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—	—	—	—
Colitis	Gastrointestinal disorders	—	—	—	—	—	—
Gastrointestinal haemorrhage	Gastrointestinal disorders	—	—	—	—	—	—
Cholecystitis acute	Hepatobiliary disorders	—	—	—	—	—	—
Device related infection	Infections and infestations	—	—	—	—	—	—
Genital herpes zoster	Infections and infestations	—	—	—	—	—	—
Infected bite	Infections and infestations	—	—	—	—	—	—
Pneumococcal infection	Infections and infestations	—	—	—	—	—	—
Respiratory tract infection	Infections and infestations	—	—	—	—	—	—
Fracture	Injury, poisoning and procedural complications	—	—	—	—	—	—
Infusion related reaction	Injury, poisoning and procedural complications	—	—	—	—	—	—
Bone cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—
Myelodysplastic syndrome	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—
Acute kidney injury	Renal and urinary disorders	—	—	—	—	—	—
Ureterolithiasis	Renal and urinary disorders	—	—	—	—	—	—
Respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—

Other adverse events (19 terms — click to expand)

Reaction	System	Total	FL Subtype	DLBCL Subtype	MCL Subtype	Other iNHL	FL + Other iNHL
Infusion-related reaction	Injury, poisoning and procedural complications	—	—	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Lymphadenopathy	Blood and lymphatic system disorders	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—
Bronchitis	Infections and infestations	—	—	—	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—

Most-reported serious reactions: Disease progression, Pneumonia, Anaemia, Herpes zoster, Febrile neutropenia, Cardiac failure, Vision blurred, Abdominal pain upper.

Data from ClinicalTrials.gov NCT01685008 adverse events section.

Sponsor's own description

This is an open-label, multicenter study to characterize the safety and efficacy of the human anti-CD19 antibody MOR00208 in adult patients with relapsed/refractory non-Hodgkin's lymphoma (NHL) who have received at least 1 prior therapy containing rituximab (at least once).

Publications & conference data

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

1. Phase IIa study of the CD19 antibody MOR208 in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma.
   Jurczak W, Zinzani PL, Gaidano G, Goy A, et al · · 2018 · cited 107× · PMID 29444231 · DOI 10.1093/annonc/mdy056
2. Advances in targeted therapy for malignant lymphoma.
   Wang L, Qin W, Huo YJ, Li X, et al · · 2020 · cited 88× · PMID 32296035 · DOI 10.1038/s41392-020-0113-2
3. Monoclonal Antibody Therapies for Hematological Malignancies: Not Just Lineage-Specific Targets.
   Cuesta-Mateos C, Alcaraz-Serna A, Somovilla-Crespo B, Muñoz-Calleja C. · · 2017 · cited 39× · PMID 29387053 · DOI 10.3389/fimmu.2017.01936
4. Combining the best of two worlds: highly flexible chimeric antigen receptor adaptor molecules (CAR-adaptors) for the recruitment of chimeric antigen receptor T cells.
   Darowski D, Kobold S, Jost C, Klein C. · · 2019 · cited 38× · PMID 30892136 · DOI 10.1080/19420862.2019.1596511
5. The promise and perils of immunotherapy.
   Lesch S, Gill S. · · 2021 · cited 35× · PMID 34581774 · DOI 10.1182/bloodadvances.2021004453c
6. Tafasitamab for the treatment of relapsed or refractory diffuse large B-cell lymphoma.
   Salles G, Długosz-Danecka M, Ghesquières H, Jurczak W. · · 2021 · cited 35× · PMID 33554668 · DOI 10.1080/14712598.2021.1884677
7. CD19-Targeted Immunotherapies for Diffuse Large B-Cell Lymphoma.
   Gambella M, Carlomagno S, Raiola AM, Giannoni L, et al · · 2022 · cited 21× · PMID 35280988 · DOI 10.3389/fimmu.2022.837457
8. Anti-CD19 monoclonal antibodies for the treatment of relapsed or refractory B-cell malignancies: a narrative review with focus on diffuse large B-cell lymphoma.
   Zinzani PL, Minotti G. · · 2022 · cited 18× · PMID 34741682 · DOI 10.1007/s00432-021-03833-x