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

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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: MOR03087 phase 1 dose escalation; Drug: Dexamethasone; Drug: Pomalidomide; Drug: Lenalidomide; Drug: MOR03087

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 Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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: 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.; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	number (#) of patients responding (# stringent complete response + # complete response + # very good partial response + # partial response)	maximum 3 years after 1st dose
Time to Progression	Time to Progression (Kaplan Meier estimate)	patients were observed for up to 36 months
Progression-free Survival	Progression-free survival (Kaplan Meier estimates)	patients were observed up to 36 months
Duration of Response	Duration of response (Kaplan Meier estimates)	patients were observed up to 36 months
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	up to 7 days after last MOR202 dose
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	56 days

Collaborators and Investigators

• Sponsor: MorphoSys AG

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2011
• Primary Completion (Actual): August 1, 2020
• Study Completion (Actual): August 1, 2020

Study Registration Dates

• First Submitted: July 29, 2011
• First Submitted That Met QC Criteria: August 19, 2011
• First Posted (Estimate): August 22, 2011

Study Record Updates

• Last Update Posted (Actual): November 16, 2021
• Last Update Submitted That Met QC Criteria: November 12, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Pomalidomide; Multiple Myeloma; Lenalidomide; CD38; MOR03087 (MOR202)
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dexamethasone; Pomalidomide; Lenalidomide; Felzartamab
• Other Study ID Numbers: MOR202C101; DRKS00003145 (Registry Identifier: German Clinical Trail Register)