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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.

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.

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 phase 1 dose escalation

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.

MOR03087

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

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

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.

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.

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

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

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

number (#) of patients responding (# stringent complete response + # complete response + # very good partial response + # partial response)

Time to Progression (Kaplan Meier estimate)

Progression-free survival (Kaplan Meier estimates)

Duration of response (Kaplan Meier estimates)

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

MorphoSys AG

regular investigator assessment and laboratory testing

Treatment cycle 28 days, MOR03087 doses applied day 1 \& 15, initial 0.01 mg/kg, max 16 mg/kg

Part A: MOR03087 Biweekly Dose Escalation

Treatment cycle 28 days, MOR03087 doses applied day 1, 8, 15 \& 22 plus extra dose on day 4 of cycle 1, Initial MOR03087 dose 4 mg/kg, max 16 mg/kg For all parts, patients will be treated until PD or until a maximum of 3 years after first treatment.

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..

Part B: MOR03087 Weekly Dose Escalation

Treatment cycle 28 days, iv MOR03087 and oral dexamethasone (DEX) applied day 1, 8, 15 \& 22 plus extra dose on day 4 of cycle 1, initial MOR03087 dose 4 mg/kg, max 16 mg/kg. DEX dose 40 mg (≤ 75 years old) or 20 mg (\> 75 years old)

Part C: MOR03087 Plus Dexamethasone

Treatment cycle 28 days, iv MOR03087 and oral dexamethasone (DEX) applied day 1, 8, 15 \& 22 plus extra dose on day 4 of cycle 1, initial MOR03087 dose 4 mg/kg, max 16 mg/kg. DEX dose 40 mg (≤ 75 years old) or 20 mg (\> 75 years old). Pomalidomide was administered to patients orally 4 mg on days 1-21 of the 28-day cycle.

Part D: MOR03087 Plus Pomalidomide + Dexamethasone

Treatment cycle 28 days, iv MOR03087 and oral dexamethasone (DEX) applied day 1, 8, 15 \& 22 plus extra dose on day 4 of cycle 1, initial MOR03087 dose 4 mg/kg, max 16 mg/kg. DEX dose 40 mg (≤ 75 years old) or 20 mg (\> 75 years old).

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

Part E: MOR03087 Plus Lenalidomide + Dexamethasone

Treatment cycle 28 days, MOR03087 doses applied day 1, 8, 15 \& 22 plus extra dose on day 4 of cycle 1, Initial MOR03087 dose 4 mg/kg, max 16 mg/kg

Treatment cycle 28 days, iv MOR03087 and oral dexamethasone (DEX) applied day 1, 8, 15 \& 22 plus extra dose on day 4 of cycle 1, initial MOR03087 dose 8 mg/kg, max 16 mg/kg. DEX dose 40 mg (≤ 75 years old) or 20 mg (\> 75 years old). Pomalidomide was administered to patients orally 4 mg on days 1-21 of the 28-day cycle.

Treatment cycle 28 days, iv MOR03087 and oral dexamethasone (DEX) applied day 1, 8, 15 \& 22 plus extra dose on day 4 of cycle 1, initial MOR03087 dose 8 mg/kg, max 16 mg/kg. DEX dose 40 mg (≤ 75 years old) or 20 mg (\> 75 years old).

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

Total

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

Austria

Germany

Region of Enrollment

Dr Winrich Rauschning, Clinical Project Lead (external)

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

Number of Participants Who Develop Anti-MOR03087 Antibodies

Overall Response Rate

Time to Progression

Progression-free Survival

Of the total 91 patients, 26 obtained a response: 5 in part C, 10 in part D and 11 in part E. Duration of response was calculated only in these patients.

Duration of Response

Dosing at 4 mg/kg IV once weekly (incl. one add. dose on Cycle 1 Day 4)

4 mg/kg QW

Dosing at 8 mg/kg IV once weekly (incl. one add. dose on Cycle 1 Day 4)

8 mg/kg QW

Dosing at 16 mg/kg IV once weekly (incl. one add. dose on Cycle 1 Day 4)

16 mg/kg QW

Pharmakokinetics was analysed on all available data on patients receiving 4mg/kg weekly, 8mg/kg weekly and 16 mg/kg weekly irrespective in which part the patients were treated.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Phase 1/2a Study of Human Anti-CD 38 Antibody MOR03087 (MOR202) in Relapsed/Refractory Multiple Myeloma	NCT01421186	Multiple Myelom...	MOR03087 phase ... MOR03087 Dexamethasone Pomalidomide Lenalidomide	18 Years -	MorphoSys AG
A Phase 1/2a Study of Human Anti-CD 38 Antibody MOR03087 (MOR202) in Relapsed/Refractory Multiple Myeloma	NCT01421186	Multiple Myelom...	MOR03087 phase ... MOR03087 Dexamethasone Pomalidomide Lenalidomide	18 Years -	MorphoSys AG

Spots Global Cancer Trial Database for mor03087 (mor202)