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A Phase 1/2a Study of Human Anti-CD 38 Antibody MOR03087 (MOR202) in Relapsed/Refractory Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01421186
Recruitment Status : Completed
First Posted : August 22, 2011
Results First Posted : October 28, 2021
Last Update Posted : November 16, 2021
Sponsor:
Information provided by (Responsible Party):
MorphoSys AG

Study Description
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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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: MOR03087 phase 1 dose escalation Drug: MOR03087 Drug: Dexamethasone Drug: Pomalidomide Drug: Lenalidomide Phase 1 Phase 2

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 91 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 2011
Actual Primary Completion Date : August 2020
Actual Study Completion Date : August 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arms and Interventions
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Arm Intervention/treatment
Experimental: Phase 1 dose escalation

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.

 Drug: MOR03087 phase 1 dose escalation

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.


Drug: Dexamethasone
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.

Drug: Pomalidomide
Pomalidomide will be administered to patients orally 4 mg on days 1-21 of the 28-day cycle.

Drug: Lenalidomide
Lenalidomide will be administered to patients orally 25 mg on days 1-21 of the 28-day cycle.
Experimental: Phase 2a confirmatory cohorts

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.

 Drug: MOR03087
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.

Drug: Dexamethasone
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.

Drug: Pomalidomide
Pomalidomide will be administered to patients orally 4 mg on days 1-21 of the 28-day cycle.

Drug: Lenalidomide
Lenalidomide will be administered to patients orally 25 mg on days 1-21 of the 28-day cycle.


Outcome Measures
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Primary Outcome Measures :
  1. Determination of Maximum Tolerated Dose and / or Recommended Dose and Dosing Regimen of MOR03087 [ Time Frame: First cycle of treatment ]
    1. as monotherapy
    2. in combination with dexamethasone
    3. in combination with pomalidomide + dexamethasone
    4. in combination with lenalidomide + dexamethasone

  2. Number of Participants Who Develop Anti-MOR03087 Antibodies [ Time Frame: during treatment period, maximum 3 years after 1st dose ]
    Number of participants who develop anti-MOR03087 antibodies, a measure of immunogenicity


Secondary Outcome Measures :
  1. Overall Response Rate [ Time Frame: maximum 3 years after 1st dose ]
    number (#) of patients responding (# stringent complete response + # complete response + # very good partial response + # partial response)

  2. Time to Progression [ Time Frame: patients were observed for up to 36 months ]
    Time to Progression (Kaplan Meier estimate)

  3. Progression-free Survival [ Time Frame: patients were observed up to 36 months ]
    Progression-free survival (Kaplan Meier estimates)

  4. Duration of Response [ Time Frame: patients were observed up to 36 months ]
    Duration of response (Kaplan Meier estimates)

  5. Pharmacokinetics: Cmax - Maximum Observed Serum Concentration for MOR202 [ Time Frame: up to 7 days after last MOR202 dose ]
    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

  6. Pharmacokinetics: AUC Cycle 1+2 - Area Under the Time/Concentration Curve for MOR202 [ Time Frame: 56 days ]
    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


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female subjects 18 years and older

  2. 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

  3. 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
  4. Absolute neutrophil count (ANC) ≥ 1,000 / mm3
  5. Haemoglobin ≥ 8 g/dL
  6. Ability to comply with all study related procedures, medication use and evaluations

Exclusion Criteria:

  1. Primary refractory multiple myeloma
  2. History of significant cerebrovascular disease or sensory or motor neuropathy of toxicity grade 3 or higher
  3. Treatment with systemic investigational agent within 28 days prior to first study treatment
  4. Solitary plasmacytoma or plasma cell leukaemia
  5. Previous allogenic stem cell transplant (SCT)
  6. 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
  7. Active systemic infection
  8. Systemic disease preventing study treatment
  9. Multiple myeloma with central nervous system (CNS) involvement
  10. 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)
  11. Significant uncontrolled cardiovascular disease or cardiac insufficiency (New York Heart Association [NYHA] classes III, IV)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01421186


Locations
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Austria
AKH (Allgemeines Krankenhaus der Stadt Wien), Abteilung für Klinische Onkologie, Universitätsklinik für Innere Medizin I
Vienna, Austria, 1090
Germany
Charité - Universitätsmedizin Berlin, CBF: Campus Benjamin Franklin, CC 14: Tumormedizin, Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie
Berlin, Germany, 12200
Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus
Dresden, Germany, 01307
Medizinische Klinik 5 - Hämatologie und Internist. Onkologie, Universitätsklinikum Erlangen
Erlangen, Germany, 91054
Medizinische Universitätsklinik, Abt. Innere Medizin I
Freiburg, Germany, 79106
Universitäsklinikum Heidelberg, Klin.-Pharmakologisches Studienzentrum
Heidelberg, Germany, 69120
Sektion für Stammzell- und Immuntherapie, II. Medizinischen Klinik,
Kiel, Germany, 24105
Klinikum rechts der Isar/ Studien / III. Med. Klinik
Munich, Germany, 81675
Medizinische Klinik II, Abt. Hämatologie, Onkologie,
Tübingen, Germany, 7206
Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II, Studienambulanz für Hämatologie/Onkologie und Infektiologie
Würzburg, Germany, 97080
Sponsors and Collaborators
MorphoSys AG
  Study Documents (Full-Text)

Documents provided by MorphoSys AG:
Study Protocol  [PDF] July 17, 2017
Statistical Analysis Plan  [PDF] September 28, 2020

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: MorphoSys AG
ClinicalTrials.gov Identifier: NCT01421186    
Other Study ID Numbers: MOR202C101
DRKS00003145 ( Registry Identifier: German Clinical Trail Register )
First Posted: August 22, 2011    Key Record Dates
Results First Posted: October 28, 2021
Last Update Posted: November 16, 2021
Last Verified: July 2021
Keywords provided by MorphoSys AG:
Multiple Myeloma
MOR03087 (MOR202)
Lenalidomide
Pomalidomide
CD38
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
 Lenalidomide
Pomalidomide
Felzartamab
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunologic Factors