Back to resultsA Phase 1/2a Study of Human Anti-CD 38 Antibody MOR03087 (MOR202) in Relapsed/Refractory Multiple Myeloma
Primary Purpose
Multiple Myeloma
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
MOR03087 phase 1 dose escalation
MOR03087
Dexamethasone
Pomalidomide
Lenalidomide
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring Multiple Myeloma, MOR03087 (MOR202), Lenalidomide, Pomalidomide, CD38
Eligibility Criteria
Inclusion Criteria:
- Male or female subjects 18 years and older
Relapsed or refractory multiple myeloma defined as:
Parts A, B and C:
(i) Failure of at least 2 previous therapies which must have included an immunomodulatory agent and a proteasome inhibitor (either together or part of different therapies) (ii) All subjects must have documented progression during or after their last prior therapy for multiple myeloma
Part D:
(i) At least 2 previous therapies including lenalidomide and a proteasome inhibitor (ii) All subjects must have documented progression during or within 60 days after their last prior therapy for multiple myeloma
Part E:
(i) Received at least one previous therapy (ii) All subjects must have documented progression during or after their last prior therapy for multiple myeloma
- Presence of serum M-protein ≥ 0.5 g per 100 mL (≥ 5 g/L) and / or urine M-protein ≥ 200 mg per 24-hour period
- Absolute neutrophil count (ANC) ≥ 1,000 / mm3
- Haemoglobin ≥ 8 g/dL
- Ability to comply with all study related procedures, medication use and evaluations
Exclusion Criteria:
- Primary refractory multiple myeloma
- History of significant cerebrovascular disease or sensory or motor neuropathy of toxicity grade 3 or higher
- Treatment with systemic investigational agent within 28 days prior to first study treatment
- Solitary plasmacytoma or plasma cell leukaemia
- Previous allogenic stem cell transplant (SCT)
- Prior therapy with other monoclonal antibodies targeting the CD38 antigen or prior therapy with other IgG monoclonal antibodies within 3 months prior to first study treatment, or IgM monoclonal antibodies within 1 month prior to first study treatment
- Active systemic infection
- Systemic disease preventing study treatment
- Multiple myeloma with central nervous system (CNS) involvement
- Previous treatment with cytotoxic chemotherapy or large field radiotherapy or other myeloma specific therapy within 28 days prior to first study treatment (radiation to a single site as concurrent therapy is allowed)
- Significant uncontrolled cardiovascular disease or cardiac insufficiency (New York Heart Association [NYHA] classes III, IV)
Sites / Locations
- AKH (Allgemeines Krankenhaus der Stadt Wien), Abteilung für Klinische Onkologie, Universitätsklinik für Innere Medizin I
- Charité - Universitätsmedizin Berlin, CBF: Campus Benjamin Franklin, CC 14: Tumormedizin, Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus
- Medizinische Klinik 5 - Hämatologie und Internist. Onkologie, Universitätsklinikum Erlangen
- Medizinische Universitätsklinik, Abt. Innere Medizin I
- Universitäsklinikum Heidelberg, Klin.-Pharmakologisches Studienzentrum
- Sektion für Stammzell- und Immuntherapie, II. Medizinischen Klinik,
- Klinikum rechts der Isar/ Studien / III. Med. Klinik
- Medizinische Klinik II, Abt. Hämatologie, Onkologie,
- Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II, Studienambulanz für Hämatologie/Onkologie und Infektiologie
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Phase 1 dose escalation
Phase 2a confirmatory cohorts
Arm Description
Part A: MOR03087 dose escalation; biweekly treatment Part B: MOR03087 dose escalation; weekly treatment Part C: MOR03087 dose escalation (weekly treatment) + dexamethasone Part D: MOR03087 weekly treatment in combination with pomalidomide + dexamethasone Part E: MOR03087 weekly treatment in combination with lenalidomide + dexamethasone For all parts, patients will be treated until disease progression (PD) or until a maximum of 3 years after first treatment.
Confirmatory cohorts of MOR03087 monotherapy (plus or minus dexamethasone), in combination with pomalidomide plus dexamethasone, and in combination with lenalidomide plus dexamethasone. Following completion of Parts A, B, and C (dose escalation of MOR03087 biweekly and weekly schedules), the Maximum Tolerated Dose (MTD) or recommended dose and dosing regimen will be confirmed in a minimum of 6 subjects. Following completion of Parts D (dose escalation of MOR03087 in combination with pomalidomide + dexamethasone) and E (dose escalation of MOR03087 in combination with lenalidomide + dexamethasone), the MTD and/or recommended dose in each part will be confirmed in a minimum of 6 subjects. For all parts, patients will be treated until PD or until a maximum of 3 years after first treatment.
Outcomes
Primary Outcome Measures
Determination of Maximum Tolerated Dose and / or Recommended Dose and Dosing Regimen of MOR03087
as monotherapy
in combination with dexamethasone
in combination with pomalidomide + dexamethasone
in combination with lenalidomide + dexamethasone
Number of Participants Who Develop Anti-MOR03087 Antibodies
Number of participants who develop anti-MOR03087 antibodies, a measure of immunogenicity
Secondary Outcome Measures
Overall Response Rate
number (#) of patients responding (# stringent complete response + # complete response + # very good partial response + # partial response)
Time to Progression
Time to Progression (Kaplan Meier estimate)
Progression-free Survival
Progression-free survival (Kaplan Meier estimates)
Duration of Response
Duration of response (Kaplan Meier estimates)
Pharmacokinetics: Cmax - Maximum Observed Serum Concentration for MOR202
PK analysis for MOR202 4, 8 and 16 mg/kg IV once weekly dose groups only, since serum concentrations of MOR202 were substantially affected by target mediated drug disposition effects for remaining dose groups
Pharmacokinetics: AUC Cycle 1+2 - Area Under the Time/Concentration Curve for MOR202
PK analysis for MOR202 4, 8 and 16 mg/kg IV once weekly dose groups only, since serum concentrations of MOR202 were substantially affected by target mediated drug disposition effects for remaining dose groups
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01421186
Brief Title
A Phase 1/2a Study of Human Anti-CD 38 Antibody MOR03087 (MOR202) in Relapsed/Refractory Multiple Myeloma
Official Title
A Phase 1/2a, Open-Label, Multicentre, Dose-Escalation Study to Evaluate the Safety and Preliminary Efficacy of the Human Anti-CD 38 Antibody MOR03087 as Monotherapy and in Combination With Standard Therapy in Subjects With Relapsed/Refractory Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
July 2011 (Actual)
Primary Completion Date
August 2020 (Actual)
Study Completion Date
August 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MorphoSys AG
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is an open-label, multicentre, dose escalation study to characterize the safety and preliminary efficacy of the human anti-CD38 antibody MOR03087 (MOR202), in adult subjects with relapsed/refractory multiple myeloma, as monotherapy and in adult subjects with relapsed/refractory multiple myeloma in combination with standard therapy.
Detailed Description
The study enrolled patients aged 18 years or older with relapsed or refractory multiple myeloma and Karnofsky performance status of 60% or higher. Patients were assigned to the different treatment regimens with MOR202 ranging between 0·01 mg/kg and 16 mg/kg in a 3 + 3 design. Dose-escalation and expansion was done either with MOR202 intravenous infusions alone (MOR202 q2w [twice a week] and q1w [weekly] groups) or in combination with dexamethasone (MOR202 with dexamethasone group), with dexamethasone plus pomalidomide (MOR202 with dexamethasone plus pomalidomide group) or plus lenalidomide (MOR202 with dexamethasone plus lenalidomide group). Primary endpoints were safety, MOR202 maximum tolerated dose (or recommended dose) and regimen, and immunogenicity.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Multiple Myeloma, MOR03087 (MOR202), Lenalidomide, Pomalidomide, CD38
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
91 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Phase 1 dose escalation
Arm Type
Experimental
Arm Description
Part A: MOR03087 dose escalation; biweekly treatment
Part B: MOR03087 dose escalation; weekly treatment
Part C: MOR03087 dose escalation (weekly treatment) + dexamethasone
Part D: MOR03087 weekly treatment in combination with pomalidomide + dexamethasone
Part E: MOR03087 weekly treatment in combination with lenalidomide + dexamethasone
For all parts, patients will be treated until disease progression (PD) or until a maximum of 3 years after first treatment.
Arm Title
Phase 2a confirmatory cohorts
Arm Type
Experimental
Arm Description
Confirmatory cohorts of MOR03087 monotherapy (plus or minus dexamethasone), in combination with pomalidomide plus dexamethasone, and in combination with lenalidomide plus dexamethasone.
Following completion of Parts A, B, and C (dose escalation of MOR03087 biweekly and weekly schedules), the Maximum Tolerated Dose (MTD) or recommended dose and dosing regimen will be confirmed in a minimum of 6 subjects.
Following completion of Parts D (dose escalation of MOR03087 in combination with pomalidomide + dexamethasone) and E (dose escalation of MOR03087 in combination with lenalidomide + dexamethasone), the MTD and/or recommended dose in each part will be confirmed in a minimum of 6 subjects.
For all parts, patients will be treated until PD or until a maximum of 3 years after first treatment.
Intervention Type
Drug
Intervention Name(s)
MOR03087 phase 1 dose escalation
Intervention Description
Treatment cycles will be 28 days. Initial MOR03087 doses will be 0.01 mg/kg in part A, 4 mg/kg in parts B and C and 8 mg/kg in parts D and E; in all parts MOR03087 doses will be escalated to a maximum of 16 mg/kg. In part A, patients will receive a biweekly intravenous infusion of MOR03087 which will be administered on days 1 and 15 of the cycle. In parts B to E patients will receive a weekly intravenous infusion of MOR03087 which will be administered on days 1, 8, 15, and 22 of the cycle.
In all parts a loading dose of MOR03087 will be additionally administered on day 4 of cycle 1.
Intervention Type
Drug
Intervention Name(s)
MOR03087
Intervention Description
MOR03087 will be administered according to the Maximum Tolerated Dose (MTD) or recommended dose and dosing regimen for MOR03087 from parts A-E of the phase I dose escalation. The biweekly MOR03087 regimen as described in part A; the weekly regimen as described for parts B-E.
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Dexamethasone will be administered to patients orally; 40 mg (≤ 75 years old) or 20 mg (> 75 years old) on days 1, 8, 15, and 22 of the 28-day cycle. An additional dose will be administered in cycle 1 on day 4.
Intervention Type
Drug
Intervention Name(s)
Pomalidomide
Intervention Description
Pomalidomide will be administered to patients orally 4 mg on days 1-21 of the 28-day cycle.
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Intervention Description
Lenalidomide will be administered to patients orally 25 mg on days 1-21 of the 28-day cycle.
Primary Outcome Measure Information:
Title
Determination of Maximum Tolerated Dose and / or Recommended Dose and Dosing Regimen of MOR03087
Description
as monotherapy
in combination with dexamethasone
in combination with pomalidomide + dexamethasone
in combination with lenalidomide + dexamethasone
Time Frame
First cycle of treatment
Title
Number of Participants Who Develop Anti-MOR03087 Antibodies
Description
Number of participants who develop anti-MOR03087 antibodies, a measure of immunogenicity
Time Frame
during treatment period, maximum 3 years after 1st dose
Secondary Outcome Measure Information:
Title
Overall Response Rate
Description
number (#) of patients responding (# stringent complete response + # complete response + # very good partial response + # partial response)
Time Frame
maximum 3 years after 1st dose
Title
Time to Progression
Description
Time to Progression (Kaplan Meier estimate)
Time Frame
patients were observed for up to 36 months
Title
Progression-free Survival
Description
Progression-free survival (Kaplan Meier estimates)
Time Frame
patients were observed up to 36 months
Title
Duration of Response
Description
Duration of response (Kaplan Meier estimates)
Time Frame
patients were observed up to 36 months
Title
Pharmacokinetics: Cmax - Maximum Observed Serum Concentration for MOR202
Description
PK analysis for MOR202 4, 8 and 16 mg/kg IV once weekly dose groups only, since serum concentrations of MOR202 were substantially affected by target mediated drug disposition effects for remaining dose groups
Time Frame
up to 7 days after last MOR202 dose
Title
Pharmacokinetics: AUC Cycle 1+2 - Area Under the Time/Concentration Curve for MOR202
Description
PK analysis for MOR202 4, 8 and 16 mg/kg IV once weekly dose groups only, since serum concentrations of MOR202 were substantially affected by target mediated drug disposition effects for remaining dose groups
Time Frame
56 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female subjects 18 years and older
Relapsed or refractory multiple myeloma defined as:
Parts A, B and C:
(i) Failure of at least 2 previous therapies which must have included an immunomodulatory agent and a proteasome inhibitor (either together or part of different therapies) (ii) All subjects must have documented progression during or after their last prior therapy for multiple myeloma
Part D:
(i) At least 2 previous therapies including lenalidomide and a proteasome inhibitor (ii) All subjects must have documented progression during or within 60 days after their last prior therapy for multiple myeloma
Part E:
(i) Received at least one previous therapy (ii) All subjects must have documented progression during or after their last prior therapy for multiple myeloma
Presence of serum M-protein ≥ 0.5 g per 100 mL (≥ 5 g/L) and / or urine M-protein ≥ 200 mg per 24-hour period
Absolute neutrophil count (ANC) ≥ 1,000 / mm3
Haemoglobin ≥ 8 g/dL
Ability to comply with all study related procedures, medication use and evaluations
Exclusion Criteria:
Primary refractory multiple myeloma
History of significant cerebrovascular disease or sensory or motor neuropathy of toxicity grade 3 or higher
Treatment with systemic investigational agent within 28 days prior to first study treatment
Solitary plasmacytoma or plasma cell leukaemia
Previous allogenic stem cell transplant (SCT)
Prior therapy with other monoclonal antibodies targeting the CD38 antigen or prior therapy with other IgG monoclonal antibodies within 3 months prior to first study treatment, or IgM monoclonal antibodies within 1 month prior to first study treatment
Active systemic infection
Systemic disease preventing study treatment
Multiple myeloma with central nervous system (CNS) involvement
Previous treatment with cytotoxic chemotherapy or large field radiotherapy or other myeloma specific therapy within 28 days prior to first study treatment (radiation to a single site as concurrent therapy is allowed)
Significant uncontrolled cardiovascular disease or cardiac insufficiency (New York Heart Association [NYHA] classes III, IV)
Facility Information:
Facility Name
AKH (Allgemeines Krankenhaus der Stadt Wien), Abteilung für Klinische Onkologie, Universitätsklinik für Innere Medizin I
City
Vienna
ZIP/Postal Code
1090
Country
Austria
Facility Name
Charité - Universitätsmedizin Berlin, CBF: Campus Benjamin Franklin, CC 14: Tumormedizin, Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie
City
Berlin
ZIP/Postal Code
12200
Country
Germany
Facility Name
Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Medizinische Klinik 5 - Hämatologie und Internist. Onkologie, Universitätsklinikum Erlangen
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
Facility Name
Medizinische Universitätsklinik, Abt. Innere Medizin I
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Universitäsklinikum Heidelberg, Klin.-Pharmakologisches Studienzentrum
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Sektion für Stammzell- und Immuntherapie, II. Medizinischen Klinik,
City
Kiel
ZIP/Postal Code
24105
Country
Germany
Facility Name
Klinikum rechts der Isar/ Studien / III. Med. Klinik
City
Munich
ZIP/Postal Code
81675
Country
Germany
Facility Name
Medizinische Klinik II, Abt. Hämatologie, Onkologie,
City
Tübingen
ZIP/Postal Code
7206
Country
Germany
Facility Name
Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II, Studienambulanz für Hämatologie/Onkologie und Infektiologie
City
Würzburg
ZIP/Postal Code
97080
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
32171061
Citation
Raab MS, Engelhardt M, Blank A, Goldschmidt H, Agis H, Blau IW, Einsele H, Ferstl B, Schub N, Rollig C, Weisel K, Winderlich M, Griese J, Hartle S, Weirather J, Jarutat T, Peschel C, Chatterjee M. MOR202, a novel anti-CD38 monoclonal antibody, in patients with relapsed or refractory multiple myeloma: a first-in-human, multicentre, phase 1-2a trial. Lancet Haematol. 2020 May;7(5):e381-e394. doi: 10.1016/S2352-3026(19)30249-2. Epub 2020 Mar 11.
Results Reference
derived
Learn more about this trial
A Phase 1/2a Study of Human Anti-CD 38 Antibody MOR03087 (MOR202) in Relapsed/Refractory Multiple Myeloma
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