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

NCT01421186 | Completed Phase 1 Results DMC

• 2 other identifiers: MOR202C101DRKS00003145
• Study Type: interventional
• Target: 91
• Locations: 2 countries
• Sites: 10

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.

Conditions

Multiple Myeloma

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Determination of Maximum Tolerated Dose and / or Recommended Dose and Dosing Regimen of MOR03087

  1. as monotherapy 2. in combination with dexamethasone 3. in combination with pomalidomide + dexamethasone 4. in combination with lenalidomide + dexamethasone

  First cycle of treatment

• Number of Participants Who Develop Anti-MOR03087 Antibodies

  Number of participants who develop anti-MOR03087 antibodies, a measure of immunogenicity

  during treatment period, maximum 3 years after 1st dose

Secondary Outcomes (6)

• Overall Response Rate

  maximum 3 years after 1st dose

• Time to Progression

  patients were observed for up to 36 months

• Progression-free Survival

  patients were observed up to 36 months

• Duration of Response

  patients were observed up to 36 months

• Pharmacokinetics: Cmax - Maximum Observed Serum Concentration for MOR202

  up to 7 days after last MOR202 dose

Study Arms (2)

Phase 1 dose escalation

EXPERIMENTAL

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; Drug: Dexamethasone; Drug: Pomalidomide; Drug: Lenalidomide

Phase 2a confirmatory cohorts

EXPERIMENTAL

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; Drug: Dexamethasone; Drug: Pomalidomide; Drug: Lenalidomide

Interventions

MOR03087 phase 1 dose escalation DRUG

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.

Phase 1 dose escalation

MOR03087 DRUG

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.

Phase 2a confirmatory cohorts

Dexamethasone DRUG

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.

Phase 1 dose escalation; Phase 2a confirmatory cohorts

Pomalidomide DRUG

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

Phase 1 dose escalation; Phase 2a confirmatory cohorts

Lenalidomide DRUG

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

Phase 1 dose escalation; Phase 2a confirmatory cohorts

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• MorphoSys AG: lead

Study Sites (10)

AKH (Allgemeines Krankenhaus der Stadt Wien), Abteilung für Klinische Onkologie, Universitätsklinik für Innere Medizin I

Vienna, 1090, Austria

Location

Charité - Universitätsmedizin Berlin, CBF: Campus Benjamin Franklin, CC 14: Tumormedizin, Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie

Berlin, 12200, Germany

Location

Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus

Dresden, 01307, Germany

Location

Medizinische Klinik 5 - Hämatologie und Internist. Onkologie, Universitätsklinikum Erlangen

Erlangen, 91054, Germany

Location

Medizinische Universitätsklinik, Abt. Innere Medizin I

Freiburg im Breisgau, 79106, Germany

Location

Universitäsklinikum Heidelberg, Klin.-Pharmakologisches Studienzentrum

Heidelberg, 69120, Germany

Location

Sektion für Stammzell- und Immuntherapie, II. Medizinischen Klinik,

Kiel, 24105, Germany

Location

Klinikum rechts der Isar/ Studien / III. Med. Klinik

Munich, 81675, Germany

Location

Medizinische Klinik II, Abt. Hämatologie, Onkologie,

Tübingen, 7206, Germany

Location

Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II, Studienambulanz für Hämatologie/Onkologie und Infektiologie

Würzburg, 97080, Germany

Location

Related Publications (1)

• 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.

  PMID: 32171061 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

felzartamab; Dexamethasone; pomalidomide; Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dr Winrich Rauschning, Clinical Project Lead (external)
• Organization: MorphoSys AG

winrich.rauschning@external.morphosys.com

+4989 89927

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2011
• First Posted: August 22, 2011
• Study Start: July 1, 2011
• Primary Completion: August 1, 2020
• Study Completion: August 1, 2020
• Last Updated: November 16, 2021
• Results First Posted: October 28, 2021

Record last verified: 2021-07

Locations

AU (1); DE (9)