A Phase I/IIa Study of Human Anti-CD38 Antibody MOR03087 (MOR202) in Relapsed/Refractory Multiple Myeloma

• ClinicalTrials.gov Identifier: NCT01421186
• Recruitment Status: Active, not recruiting
• First Posted: August 22, 2011
• Last Update Posted: August 22, 2019
• Sponsor: MorphoSys AG
• Information provided by (Responsible Party): MorphoSys AG

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.

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

Study Design

• 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 I/IIa, Open-Label, Multicentre, Dose-Escalation Study to Evaluate the Safety and Preliminary Efficacy of the Human Anti-CD38 Antibody MOR03087 as Monotherapy and in Combination With Standard Therapy in Subjects With Relapsed/Refractory Multiple Myeloma
• Study Start Date: July 2011
• Estimated Primary Completion Date: September 2020
• Estimated Study Completion Date: September 2020

Arms and Interventions

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

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. Safety will be evaluated by assessing adverse events, clinical laboratory data and vital signs [ Time Frame: until PD, maximum 3 years after 1st dose ]
3. Number of participants who develop anti-MOR03087 antibodies as a measure of immunogenicity [ Time Frame: until PD, maximum 3 years after 1st dose ]

Secondary Outcome Measures :

1. Pharmacokinetics of MOR03087 +/- lenalidomide or pomalidomide (pharmacokinetic assessment comprises: C max, t max, t 1/2, Total Body Clearance (CL), AUC) [ Time Frame: until PD, maximum 3 years after 1st dose ]
2. Overall response rate, duration of response, time to progression (TTP) and progression-free survival (PFS) [ Time Frame: maximum 3 years after 1st dose ]

Eligibility Criteria

• 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

Locations

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

More Information

• Responsible Party: MorphoSys AG
• ClinicalTrials.gov Identifier: NCT01421186 History of Changes
• Other Study ID Numbers: MOR202C101; DRKS00003145 ( Registry Identifier: German Clinical Trail Register )
• First Posted: August 22, 2011
• Last Update Posted: August 22, 2019
• Last Verified: August 2019

Keywords provided by MorphoSys AG:

Multiple Myeloma; MOR03087 (MOR202); Lenalidomide; Pomalidomide; CD38

Additional relevant MeSH terms:

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; Thalidomide; Dexamethasone; Dexamethasone acetate; Lenalidomide; Pomalidomide; BB 1101; Antibodies; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists