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

NCT ID: NCT01421186

Last Updated: 2021-11-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 91 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-07-31
• Study Completion Date: 2020-08-31

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.

Conditions

Multiple Myeloma

Keywords

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

MOR03087 phase 1 dose escalation

Intervention Type: 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.

Dexamethasone

Intervention Type: 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.

Pomalidomide

Intervention Type: DRUG

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

Lenalidomide

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

MOR03087

Intervention Type: 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.

Dexamethasone

Intervention Type: 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.

Pomalidomide

Intervention Type: DRUG

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

Lenalidomide

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Pomalidomide

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

Intervention Type: DRUG

Lenalidomide

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

Intervention Type: DRUG

Eligibility 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

MorphoSys AG

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

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

Vienna, , Austria

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

Berlin, , Germany

Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus

Dresden, , Germany

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

Erlangen, , Germany

Medizinische Universitätsklinik, Abt. Innere Medizin I

Freiburg im Breisgau, , Germany

Universitäsklinikum Heidelberg, Klin.-Pharmakologisches Studienzentrum

Heidelberg, , Germany

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

Kiel, , Germany

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

Munich, , Germany

Medizinische Klinik II, Abt. Hämatologie, Onkologie,

Tübingen, , Germany

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

Würzburg, , Germany

Countries

Austria; Germany

References

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.

Reference Type: DERIVED

PMID: 32171061 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

DRKS00003145

Identifier Type: REGISTRY

Identifier Source: secondary_id

MOR202C101

Identifier Type: -

Identifier Source: org_study_id