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

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01421186
• Other study ID #: MOR202C101
• Secondary ID: DRKS00003145
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: July 2011
• Est. completion date: August 2020

Study information

• Verified date: July 2021
• Source: MorphoSys AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 91
• Est. completion date: August 2020
• Est. primary completion date: August 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

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.
• 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.
• 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.
• Pomalidomide
Pomalidomide will be administered to patients orally 4 mg on days 1-21 of the 28-day cycle.
• Lenalidomide
Lenalidomide will be administered to patients orally 25 mg on days 1-21 of the 28-day cycle.

Locations

Country	Name	City	State
Austria	AKH (Allgemeines Krankenhaus der Stadt Wien), Abteilung für Klinische Onkologie, Universitätsklinik für Innere Medizin I	Vienna
Germany	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
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

Sponsors (1)

Lead Sponsor	Collaborator
MorphoSys AG

Countries where clinical trial is conducted

Austria,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Overall Response Rate	number (#) of patients responding (# stringent complete response + # complete response + # very good partial response + # partial response)	maximum 3 years after 1st dose
Secondary	Time to Progression	Time to Progression (Kaplan Meier estimate)	patients were observed for up to 36 months
Secondary	Progression-free Survival	Progression-free survival (Kaplan Meier estimates)	patients were observed up to 36 months
Secondary	Duration of Response	Duration of response (Kaplan Meier estimates)	patients were observed up to 36 months
Secondary	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
Secondary	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