Open Label Study to Evaluate the Safety and Efficacy of Lenalidomide With MOR00208 in Patients With R-R DLBCL (L-MIND)

• ClinicalTrials.gov Identifier: NCT02399085
• Recruitment Status: Completed
• First Posted: March 26, 2015
• Results First Posted: February 5, 2020
• Last Update Posted: October 23, 2023
• Sponsor: MorphoSys AG
• Information provided by (Responsible Party): MorphoSys AG

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Diffuse Large B-cell Lymphoma
• Interventions: Drug: Tafasitamab; Drug: Lenalidomide
• Enrollment: 81

Participant Flow

Recruitment Details	The participants were enrolled into this study at sites in Hungary, Belgium, Czechia, France, Poland, Italy, Germany, Spain, United Kingdom, and the United States.
Pre-assignment Details

Arm/Group Title	Treatment (MOR00208, Lenalidomide)
Arm/Group Description	MOR00208: MOR00208 was administered via IV infusion at a dose of 12 mg/kg. For the first three cycles (Cycles 1 to 3) of the study each cycle consisted of a MOR00208 infusion on Day 1, Day 8, Day 15 and Day 22 of the cycle. Additionally, a loading dose was administered on Day 4 of Cycle 1. Thereafter MOR00208 was administered on a bi-weekly (every 14 days) basis with infusions on Day 1 and Day 15 of each 28-day cycle. LEN: Participants self-administered a starting dose of 25 mg oral LEN daily on Days 1-21 of each cycle, for up to 12 cycles in total. LEN dose could be modified in a de-escalating fashion or discontinued based upon clinical and laboratory findings. On days when both study drugs were given together, LEN was administered prior to MOR00208.
Period Title: Overall Study
Started	81
Received MOR00208 + LEN	80
Received MOR00208 Only	1
Completed: Participants Who Were Still on Treatment at EOS	8
Not Completed: Participants Who Were no Longer Receiving Treatment at EOS	73
Completed	8
Not Completed	73
Reason Not Completed
Adverse Event	16
Death	2
Withdrawal by Subject	8
Progressive disease/ Disease relapse	42
Physician Decision	5

Baseline Characteristics

Arm/Group Title		Treatment (MOR00208, Lenalidomide)
Arm/Group Description		MOR00208: MOR00208 was administered via IV infusion at a dose of 12 mg/kg. For the first three cycles (Cycles 1 to 3) of the study each cycle consisted of a MOR00208 infusion on Day 1, Day 8, Day 15 and Day 22 of the cycle. Additionally, a loading dose was administered on Day 4 of Cycle 1. Thereafter MOR00208 was administered on a bi-weekly (every 14 days) basis with infusions on Day 1 and Day 15 of each 28-day cycle. LEN: Participants self-administered a starting dose of 25 mg oral LEN daily on Days 1-21 of each cycle, for up to 12 cycles in total. LEN dose could be modified in a de-escalating fashion or discontinued based upon clinical and laboratory findings. On days when both study drugs were given together, LEN was administered prior to MOR00208.
Overall Number of Baseline Participants		81
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	81 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	23 28.4%
	>=65 years	58 71.6%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	81 participants
		69.3 (9.53)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	81 participants
	Female	37 45.7%
	Male	44 54.3%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	81 participants
	American Indian or Alaska Native	0 0.0%
	Asian	2 2.5%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	0 0.0%
	White	72 88.9%
	More than one race	0 0.0%
	Unknown or Not Reported	7 8.6%
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	81 participants
Hungary		7 8.6%
Belgium		5 6.2%
United States		6 7.4%
Czechia		3 3.7%
Poland		7 8.6%
Italy		13 16.0%
United Kingdom		5 6.2%
France		9 11.1%
Germany		11 13.6%
Spain		15 18.5%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Best Objective Response Rate (ORR)
Description	ORR = complete response [CR] + partial response [PR]; Independent Radiology/Clinical Review Committee (IRC) Evaluation. ORR after MOR00208 and Lenalidomide combination therapy assessed by the IRC evaluation. ORR was defined as the number of participants of the total number of participants treated with MOR00208 + LEN with CR or PR as best response achieved at any time during the study.
Time Frame	Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS): The FAS included all participant who received at least one dose of MOR00208 and at least one dose of LEN. This meant that both study drugs had to be administered at least once.

Arm/Group Title	Treatment (MOR00208, Lenalidomide)
Arm/Group Description:	MOR00208: MOR00208 was administered via IV infusion at a dose of 12 mg/kg. For the first three cycles (Cycles 1 to 3) of the study each cycle consisted of a MOR00208 infusion on Day 1, Day 8, Day 15 and Day 22 of the cycle. Additionally, a loading dose was administered on Day 4 of Cycle 1. Thereafter MOR00208 was administered on a bi-weekly (every 14 days) basis with infusions on Day 1 and Day 15 of each 28-day cycle. LEN: Participants self-administered a starting dose of 25 mg oral LEN daily on Days 1-21 of each cycle, for up to 12 cycles in total. LEN dose could be modified in a de-escalating fashion or discontinued based upon clinical and laboratory findings.
Overall Number of Participants Analyzed	80
Measure Type: Count of Participants; Unit of Measure: Participants
Approximately 4.5 years after first participant enrolled	46 57.5%
Approximately 6.5 years after first participant enrolled	46 57.5%

2. Secondary Outcome

Title	Duration of Response (DoR) by IRC Evaluation
Description	DoR [months] = (date of assessment of tumor progression or death - date of assessment of first documented response of (CR or PR) + 1)/30.4375.
Time Frame	Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled

Outcome Measure Data

Analysis Population Description

FAS: The FAS included all participants who received at least one dose of MOR00208 and at least one dose of LEN. This meant that both study drugs had to be administered at least once. Inclusive of participants with available data.

Arm/Group Title	Treatment (MOR00208, Lenalidomide)
Arm/Group Description:	MOR00208: MOR00208 was administered via IV infusion at a dose of 12 mg/kg. For the first three cycles (Cycles 1 to 3) of the study each cycle consisted of a MOR00208 infusion on Day 1, Day 8, Day 15 and Day 22 of the cycle. Additionally, a loading dose was administered on Day 4 of Cycle 1. Thereafter MOR00208 was administered on a bi-weekly (every 14 days) basis with infusions on Day 1 and Day 15 of each 28-day cycle. LEN: Participants self-administered a starting dose of 25 mg oral LEN daily on Days 1-21 of each cycle, for up to 12 cycles in total. LEN dose could be modified in a de-escalating fashion or discontinued based upon clinical and laboratory findings.
Overall Number of Participants Analyzed	46
Median (95% Confidence Interval); Unit of Measure: Months
Approximately 4.5 years after first participant enrolled	43.9 [1]; (26.1 to NA)
Approximately 6.5 years after first participant enrolled	NA [2]; (33.8 to NA)

[1]

[Not available]. Upper limit not reached due to insufficient number of events at later stages of follow-up.

[2]

[Not available]. Median and upper limit not reached due to insufficient number of events at later stages of follow-up.

3. Secondary Outcome

Title	DoR by Investigator (INV) Evaluation
Description	DoR [months] = (date of assessment of tumour progression or death - date of assessment of first documented response of (CR or PR) + 1)/30.4375.
Time Frame	Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled

Outcome Measure Data

Analysis Population Description

FAS: The FAS included all participants who received at least one dose of MOR00208 and at least one dose of LEN. This meant that both study drugs had to be administered at least once. Inclusive of participants with available data.

Arm/Group Title	Tafasitamab (MOR00208) + Lenalidomide (LEN)
Arm/Group Description:	MOR00208: MOR00208 was administered via IV infusion at a dose of 12 mg/kg. For the first three cycles (Cycles 1 to 3) of the study each cycle consisted of a MOR00208 infusion on Day 1, Day 8, Day 15 and Day 22 of the cycle. Additionally, a loading dose was administered on Day 4 of Cycle 1. Thereafter MOR00208 was administered on a bi-weekly (every 14 days) basis with infusions on Day 1 and Day 15 of each 28-day cycle. LEN: Participants self-administered a starting dose of 25 mg oral LEN daily on Days 1-21 of each cycle, for up to 12 cycles in total. LEN dose could be modified in a de-escalating fashion or discontinued based upon clinical and laboratory findings.
Overall Number of Participants Analyzed	52
Median (95% Confidence Interval); Unit of Measure: Months
Approximately 4.5 years after first participant enrolled	43.9 [1]; (13.9 to NA)
Approximately 6.5 years after first participant enrolled	43.4 [1]; (14.1 to NA)

[1]

Not available. Upper limit not reached due to insufficient number of events at later stages of follow-up.

4. Secondary Outcome

Title	Progression-free Survival (PFS) by IRC Evaluation
Description	PFS time was defined as the time (in months) from the date of the first administration of any study drug to the date of tumor progression or death from any cause.
Time Frame	Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled

Outcome Measure Data

Analysis Population Description

FAS: The FAS included all participants who received at least one dose of MOR00208 and at least one dose of LEN. This meant that both study drugs had to be administered at least once. Inclusive of participants with available data.

Arm/Group Title	Tafasitamab (MOR00208) + Lenalidomide (LEN)
Arm/Group Description:	MOR00208: MOR00208 was administered via IV infusion at a dose of 12 mg/kg. For the first three cycles (Cycles 1 to 3) of the study each cycle consisted of a MOR00208 infusion on Day 1, Day 8, Day 15 and Day 22 of the cycle. Additionally, a loading dose was administered on Day 4 of Cycle 1. Thereafter MOR00208 was administered on a bi-weekly (every 14 days) basis with infusions on Day 1 and Day 15 of each 28-day cycle. LEN: Participants self-administered a starting dose of 25 mg oral LEN daily on Days 1-21 of each cycle, for up to 12 cycles in total. LEN dose could be modified in a de-escalating fashion or discontinued based upon clinical and laboratory findings. On days when both study drugs were given together, LEN was administered prior to MOR00208.
Overall Number of Participants Analyzed	42
Median (95% Confidence Interval); Unit of Measure: Months
Approximately 4.5 years after first participant enrolled	11.6; (6.3 to 45.7)
Approximately 6.5 years after first participant enrolled	11.6; (5.7 to 45.7)

5. Secondary Outcome

Title	PFS by INV Evaluation
Description	PFS time was defined as the time (in months) from the date of the first administration of any study drug to the date of tumor progression or death from any cause.
Time Frame	Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled

Outcome Measure Data

Analysis Population Description

FAS: The FAS includes all participants who received at least one dose of MOR00208 and one dose of LEN. This meant that both study drugs had to be administered at least once. Inclusive of participants with available data.

Arm/Group Title		Tafasitamab (MOR00208) + Lenalidomide (LEN)
Arm/Group Description:		MOR00208: MOR00208 was administered via IV infusion at a dose of 12 mg/kg. For the first three cycles (Cycles 1 to 3) of the study each cycle consisted of a MOR00208 infusion on Day 1, Day 8, Day 15 and Day 22 of the cycle. Additionally, a loading dose was administered on Day 4 of Cycle 1. Thereafter MOR00208 was administered on a bi-weekly (every 14 days) basis with infusions on Day 1 and Day 15 of each 28-day cycle. LEN: Participants self-administered a starting dose of 25 mg oral LEN daily on Days 1-21 of each cycle, for up to 12 cycles in total. LEN dose could be modified in a de-escalating fashion or discontinued based upon clinical and laboratory findings. On days when both study drugs were given together, LEN was administered prior to MOR00208.
Overall Number of Participants Analyzed		49
Median (95% Confidence Interval); Unit of Measure: Months
Approximately 4.5 years after first participant enrolled	Number Analyzed	46 participants
		9.1; (5.5 to 28.0)
Approximately 6.5 years after first participant enrolled	Number Analyzed	49 participants
		9.1; (5.5 to 45.5)

6. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time from the date of the first administration of any study drug until death from any cause (documented by the date of death).
Time Frame	Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled

Outcome Measure Data

Analysis Population Description

FAS: The FAS includes all participants who received at least one dose of MOR00208 and one dose of LEN. This means that both study drugs must have been applied at least once. Inclusive of participants with available data.

Arm/Group Title		Tafasitamab (MOR00208) + Lenalidomide (LEN)
Arm/Group Description:		MOR00208: MOR00208 was administered via IV infusion at a dose of 12 mg/kg. For the first three cycles (Cycles 1 to 3) of the study each cycle consisted of a MOR00208 infusion on Day 1, Day 8, Day 15 and Day 22 of the cycle. Additionally, a loading dose was administered on Day 4 of Cycle 1. Thereafter MOR00208 was administered on a bi-weekly (every 14 days) basis with infusions on Day 1 and Day 15 of each 28-day cycle. LEN: Participants self-administered a starting dose of 25 mg oral LEN daily on Days 1-21 of each cycle, for up to 12 cycles in total. LEN dose could be modified in a de-escalating fashion or discontinued based upon clinical and laboratory findings. On days when both study drugs were given together, LEN was administered prior to MOR00208.
Overall Number of Participants Analyzed		44
Median (95% Confidence Interval); Unit of Measure: Months
Approximately 4.5 years after first participant enrolled	Number Analyzed	41 participants
		33.5 [1]; (18.3 to NA)
Approximately 6.5 years after first participant enrolled	Number Analyzed	44 participants
		33.5 [1]; (18.3 to NA)

[1]

Not available. Upper limit not reached due to insufficient number of events at later stages of follow-up.

7. Secondary Outcome

Title	Disease Control Rate (DCR) by IRC Evaluation
Description	DCR = CR + PR + SD (Stable disease); IRC Evaluation DCR was defined as the number of participants having CR, PR or SD based on the best objective response achieved at any time during the study.
Time Frame	Approximately 2.5 years after first participant enrolled

Outcome Measure Data

Analysis Population Description

FAS: The FAS included all participants who received at least one dose of MOR00208 and at least one dose of LEN. This meant that both study drugs had to be administered at least once.

Arm/Group Title	Tafasitamab (MOR00208) + Lenalidomide (LEN)
Arm/Group Description:	MOR00208: MOR00208 was administered via IV infusion at a dose of 12 mg/kg. For the first three cycles (Cycles 1 to 3) of the study each cycle consisted of a MOR00208 infusion on Day 1, Day 8, Day 15 and Day 22 of the cycle. Additionally, a loading dose was administered on Day 4 of Cycle 1. Thereafter MOR00208 was administered on a bi-weekly (every 14 days) basis with infusions on Day 1 and Day 15 of each 28-day cycle. LEN: Participants self-administered a starting dose of 25 mg oral LEN daily on Days 1-21 of each cycle, for up to 12 cycles in total. LEN dose could be modified in a de-escalating fashion or discontinued based upon clinical and laboratory findings. On days when both study drugs were given together, LEN was administered prior to MOR00208.
Overall Number of Participants Analyzed	80
Measure Type: Count of Participants; Unit of Measure: Participants
	59 73.8%

8. Secondary Outcome

Title	DCR by INV Evaluation
Description	DCR = CR + PR + SD (Stable disease); IRC Evaluation DCR was defined as the number of participants having CR, PR or SD based on the best objective response achieved at any time during the study.
Time Frame	Approximately 2.5 years after first participant enrolled

Outcome Measure Data

Analysis Population Description

FAS: The FAS included all participants who received at least one dose of MOR00208 and at least one dose of LEN. This meant that both study drugs had to be administered at least once.

Arm/Group Title	Tafasitamab (MOR00208) + Lenalidomide (LEN)
Arm/Group Description:	MOR00208: MOR00208 was administered via IV infusion at a dose of 12 mg/kg. For the first three cycles (Cycles 1 to 3) of the study each cycle consisted of a MOR00208 infusion on Day 1, Day 8, Day 15 and Day 22 of the cycle. Additionally, a loading dose was administered on Day 4 of Cycle 1. Thereafter MOR00208 was administered on a bi-weekly (every 14 days) basis with infusions on Day 1 and Day 15 of each 28-day cycle. LEN: Participants self-administered a starting dose of 25 mg oral LEN daily on Days 1-21 of each cycle, for up to 12 cycles in total. LEN dose could be modified in a de-escalating fashion or discontinued based upon clinical and laboratory findings. On days when both study drugs were given together, LEN was administered prior to MOR00208.
Overall Number of Participants Analyzed	80
Measure Type: Count of Participants; Unit of Measure: Participants
	60 75.0%

9. Secondary Outcome

Title	Time to Progression (TTP) by IRC Evaluation
Description	TTP is defined as the time from the first administration of any study drug until documented DLBCL progression or death as a result of lymphoma.
Time Frame	Approximately 2.5 years after first participant enrolled

Outcome Measure Data

Analysis Population Description

FAS: The FAS included all participants who received at least one dose of MOR00208 and at least one dose of LEN. This meant that both study drugs had to be administered at least once. Inclusive of participants with available data.

Arm/Group Title	Tafasitamab (MOR00208) + Lenalidomide (LEN)
Arm/Group Description:	MOR00208: MOR00208 was administered via IV infusion at a dose of 12 mg/kg. For the first three cycles (Cycles 1 to 3) of the study each cycle consisted of a MOR00208 infusion on Day 1, Day 8, Day 15 and Day 22 of the cycle. Additionally, a loading dose was administered on Day 4 of Cycle 1. Thereafter MOR00208 was administered on a bi-weekly (every 14 days) basis with infusions on Day 1 and Day 15 of each 28-day cycle. LEN: Participants self-administered a starting dose of 25 mg oral LEN daily on Days 1-21 of each cycle, for up to 12 cycles in total. LEN dose could be modified in a de-escalating fashion or discontinued based upon clinical and laboratory findings. On days when both study drugs were given together, LEN was administered prior to MOR00208.
Overall Number of Participants Analyzed	35
Median (95% Confidence Interval); Unit of Measure: Months
	16.2 [1]; (7.4 to NA)

[1]

Not available. Upper limit not reached due to insufficient number of events at later stages of follow-up.

10. Secondary Outcome

Title	TTP by INV Evaluation
Description	TTP is defined as the time from the first administration of any study drug until documented DLBCL progression or death as a result of lymphoma.
Time Frame	Approximately 2.5 years after first participant enrolled

Outcome Measure Data

Analysis Population Description

FAS: The FAS included all participants who received at least one dose of MOR00208 and at least one dose of LEN. This meant that both study drugs had to be administered at least once. Inclusive of participants with available data.

Arm/Group Title	Tafasitamab (MOR00208) + Lenalidomide (LEN)
Arm/Group Description:	MOR00208: MOR00208 was administered via IV infusion at a dose of 12 mg/kg. For the first three cycles (Cycles 1 to 3) of the study each cycle consisted of a MOR00208 infusion on Day 1, Day 8, Day 15 and Day 22 of the cycle. Additionally, a loading dose was administered on Day 4 of Cycle 1. Thereafter MOR00208 was administered on a bi-weekly (every 14 days) basis with infusions on Day 1 and Day 15 of each 28-day cycle. LEN: Participants self-administered a starting dose of 25 mg oral LEN daily on Days 1-21 of each cycle, for up to 12 cycles in total. LEN dose could be modified in a de-escalating fashion or discontinued based upon clinical and laboratory findings. On days when both study drugs were given together, LEN was administered prior to MOR00208.
Overall Number of Participants Analyzed	40
Median (95% Confidence Interval); Unit of Measure: Months
	14.1 [1]; (6.3 to NA)

[1]

Not available. Upper limit not reached due to insufficient number of events at later stages of follow-up.

11. Secondary Outcome

Title	Time to Next Treatment (TTNT)
Description	Kaplan-Meier analysis of TTNT in FAS population. TTNT is defined as the time from the first administration of any study drug to the institution of next anti-neoplastic therapy (for any reason including disease progression, treatment toxicity and participant preference) or death of any cause, whatever comes first.
Time Frame	Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled

Outcome Measure Data

Analysis Population Description

FAS: The FAS includes all participants who received at least one dose of MOR00208 and one dose of LEN. This means that both study drugs must have been applied at least once. Inclusive of participants with available data.

Arm/Group Title		Tafasitamab (MOR00208) + Lenalidomide (LEN)
Arm/Group Description:		MOR00208: MOR00208 was administered via IV infusion at a dose of 12 mg/kg. For the first three cycles (Cycles 1 to 3) of the study each cycle consisted of a MOR00208 infusion on Day 1, Day 8, Day 15 and Day 22 of the cycle. Additionally, a loading dose was administered on Day 4 of Cycle 1. Thereafter MOR00208 was administered on a bi-weekly (every 14 days) basis with infusions on Day 1 and Day 15 of each 28-day cycle. LEN: Participants self-administered a starting dose of 25 mg oral LEN daily on Days 1-21 of each cycle, for up to 12 cycles in total. LEN dose could be modified in a de-escalating fashion or discontinued based upon clinical and laboratory findings. On days when both study drugs were given together, LEN was administered prior to MOR00208.
Overall Number of Participants Analyzed		55
Median (95% Confidence Interval); Unit of Measure: Months
Approximately 4.5 years after first participant enrolled	Number Analyzed	51 participants
		12.1; (7.3 to 24.7)
Approximately 6.5 years after first participant enrolled	Number Analyzed	55 participants
		12.5; (7.3 to 28)

12. Secondary Outcome

Title	Event-free Survival (EFS) by IRC Evaluation
Description	EFS is defined as the time (in months) from the date of the first administration of any study drug to the date of tumour progression, first initiation of a new non-study anti-neoplastic therapy or death from any cause whichever comes first.
Time Frame	Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled

Outcome Measure Data

Analysis Population Description

FAS: The FAS includes all participants who received at least one dose of MOR00208 and one dose of LEN. This means that both study drugs must have been applied at least once. Inclusive of participants with available data.

Arm/Group Title		Tafasitamab (MOR00208) + Lenalidomide (LEN)
Arm/Group Description:		MOR00208: MOR00208 was administered via IV infusion at a dose of 12 mg/kg. For the first three cycles (Cycles 1 to 3) of the study each cycle consisted of a MOR00208 infusion on Day 1, Day 8, Day 15 and Day 22 of the cycle. Additionally, a loading dose was administered on Day 4 of Cycle 1. Thereafter MOR00208 was administered on a bi-weekly (every 14 days) basis with infusions on Day 1 and Day 15 of each 28-day cycle. LEN: Participants self-administered a starting dose of 25 mg oral LEN daily on Days 1-21 of each cycle, for up to 12 cycles in total. LEN dose could be modified in a de-escalating fashion or discontinued based upon clinical and laboratory findings. On days when both study drugs were given together, LEN was administered prior to MOR00208.
Overall Number of Participants Analyzed		55
Median (95% Confidence Interval); Unit of Measure: Months
Approximately 4.5 years after first participant enrolled	Number Analyzed	53 participants
		8.7; (5.3 to 21.0)
Approximately 6.5 years after first participant enrolled	Number Analyzed	55 participants
		9.1; (5.3 to 23.5)

13. Secondary Outcome

Title	Serum Drug Levels of MOR00208
Description	The pharmacokinetics (PK) profile of MOR00208 was investigated by quantifying serum drug levels at baseline and after repeated IV administrations for up to 24 treatment cycles using sparse sampling. MOR00208 PK sample was taken pre-dose and 1 hour ± 10 min after the end of MOR00208 infusion for Cycle 1 to Cycle 23. MOR00208 PK sample (pre-dose only) were taken in odd numbered additional treatment cycles only (e.g., treatment Cycles 13, 15,17, 19, 21, 23).
Time Frame	Cycle 1 Days 1, 4, 15 predose and 1 hr post-dose; Cycle 2 Days 1, 15 predose and 1 hr post-dose; Cycle 3 Days 1, 15 predose and 1 hr post-dose; Cycles 4, 5, 6, 7, 9, 11,13, 15, 17, 19, 21, 23 Day 1 predose; End of Treatment

Outcome Measure Data

Analysis Population Description

PK analysis set (PKAS): The PKAS included all participants who received at least one dose of MOR00208 and had at least one quantifiable MOR00208 serum concentration.

Number analyzed includes only participants with data at each timepoint.

Arm/Group Title		Tafasitamab (MOR00208) + Lenalidomide (LEN)
Arm/Group Description:		MOR00208: MOR00208 was administered via IV infusion at a dose of 12 mg/kg. For the first three cycles (Cycles 1 to 3) of the study each cycle consisted of a MOR00208 infusion on Day 1, Day 8, Day 15 and Day 22 of the cycle. Additionally, a loading dose was administered on Day 4 of Cycle 1. Thereafter MOR00208 was administered on a bi-weekly (every 14 days) basis with infusions on Day 1 and Day 15 of each 28-day cycle. LEN: Participants self-administered a starting dose of 25 mg oral LEN daily on Days 1-21 of each cycle, for up to 12 cycles in total. LEN dose could be modified in a de-escalating fashion or discontinued based upon clinical and laboratory findings. On days when both study drugs were given together, LEN was administered prior to MOR00208.
Overall Number of Participants Analyzed		81
Mean (Standard Deviation); Unit of Measure: ng/mL
Cycle 1 Day 1 (Predose)	Number Analyzed	79 participants
		6.7 (53.09)
Cycle 1 Day 1 (1 hour post dose)	Number Analyzed	71 participants
		249075.9 (53724.93)
Cycle 1 Day 4 (pre-dose)	Number Analyzed	73 participants
		126306.8 (39105.37)
Cycle 1 Day 4 (1 hour post-dose)	Number Analyzed	65 participants
		363626.2 (82971.54)
Cycle 1 Day 15 (pre dose)	Number Analyzed	75 participants
		157722.3 (50655.86)
Cycle 1 Day 15 (1 hour post-dose)	Number Analyzed	70 participants
		396262.1 (97215.09)
Cycle 2 Day 1 (predose)	Number Analyzed	71 participants
		181870.8 (72582.62)
Cycle 2 Day 1 (1 hour post-dose)	Number Analyzed	62 participants
		439788.2 (126930.55)
Cycle 2 Day 15 (Pre Dose)	Number Analyzed	63 participants
		217846.9 (77799.93)
Cycle 2 Day 15 (1 hour post-dose) )	Number Analyzed	59 participants
		442940.2 (85475.90)
Cycle 3 Day 1 (predose)	Number Analyzed	61 participants
		208520.6 (68866.46)
Cycle 3 Day 1 (1 hour post-dose)	Number Analyzed	53 participants
		466135.8 (112647.31)
Cycle 3 Day 15 (predose)	Number Analyzed	51 participants
		223909.4 (85170.91)
Cycle 3 Day 15 (1 hour post-dose)	Number Analyzed	44 participants
		455635.0 (104198.64)
Cycle 4 Day 1 (predose) )	Number Analyzed	52 participants
		216328.4 (94553.25)
Cycle 5 Day 1 (pre dose)	Number Analyzed	51 participants
		142134.4 (72691.16)
Cycle 6 Day 1 (pre dose)	Number Analyzed	49 participants
		115132.3 (55774.77)
Cycle 7 Day 1 (pre dose)	Number Analyzed	49 participants
		114661.5 (73328.15)
Cycle 9 Day 1 (pre dose)	Number Analyzed	40 participants
		108640.4 (52282.72)
Cycle 11 Day 1 (pre dose)	Number Analyzed	34 participants
		126472.0 (64872.47)
Cycle 13 Day 1 (pre dose)	Number Analyzed	31 participants
		100853.5 (61229.42)
Cycle 15 Day 1 (pre dose)	Number Analyzed	30 participants
		159676.5 (61199.32)
Cycle 17 Day 1 (pre dose)	Number Analyzed	25 participants
		175855.1 (64592.17)
Cycle 19 Day 1 (pre dose)	Number Analyzed	21 participants
		197045.0 (69962.05)
Cycle 21 Day 1 (pre dose)	Number Analyzed	19 participants
		197228.0 (53222.03)
Cycle 23 Day 1 (pre dose)	Number Analyzed	15 participants
		224253.3 (64686.85)
End of Treatment	Number Analyzed	39 participants
		141240.7 (114804.40)

14. Secondary Outcome

Title	Number of Participants Who Developed Anti-MOR00208 Antibodies
Description	The Anti-MOR00208 Antibodies were investigated by quantifying serum drug levels at baseline and after repeated intravenous (IV) administrations planned for up to 24 treatment cycles using sparse sampling. Anti-MOR00208 antibody sample (pre-dose only) were taken in odd numbered additional treatment cycles only (e.g., treatment Cycles 13, 15,17, 19, 21,23).
Time Frame	Baseline, Up to a maximum of 23 cycles.

Outcome Measure Data

Analysis Population Description

Immunogenicity analysis set (IAS): The IAS included participants who had at least one anti-MOR00208 antibody assessment.

Arm/Group Title	Tafasitamab (MOR00208) + Lenalidomide (LEN)
Arm/Group Description:	MOR00208: MOR00208 was administered via IV infusion at a dose of 12 mg/kg. For the first three cycles (Cycles 1 to 3) of the study each cycle consisted of a MOR00208 infusion on Day 1, Day 8, Day 15 and Day 22 of the cycle. Additionally, a loading dose was administered on Day 4 of Cycle 1. Thereafter MOR00208 was administered on a bi-weekly (every 14 days) basis with infusions on Day 1 and Day 15 of each 28-day cycle. LEN: Participants self-administered a starting dose of 25 mg oral LEN daily on Days 1-21 of each cycle, for up to 12 cycles in total. LEN dose could be modified in a de-escalating fashion or discontinued based upon clinical and laboratory findings. On days when both study drugs were given together, LEN was administered prior to MOR00208.
Overall Number of Participants Analyzed	81
Measure Type: Count of Participants; Unit of Measure: Participants
Yes (Treatment-emergent ADAs)	0 0.0%
No (Negative baseline and post baseline results)	72 88.9%
Not evaluable (Positive baseline results)	2 2.5%
Missing (No post baseline results available)	7 8.6%

15. Secondary Outcome

Title	Number of Participants That Experienced Treatment-emergent Adverse Events (TEAEs)
Description	TEAEs are defined as any adverse event reported in the following time interval (including the lower and upper limits): date of first administration of study treatment; date of last administration of study treatment + 30 days, or if they are considered to be related to the study drug.
Time Frame	Approximately 6.5 years after first participant enrolled

Outcome Measure Data

Analysis Population Description

Safety analysis set (SAF):

The SAF includes all participants who received at least one dose of MOR00208 or LEN and had at least one post-baseline safety assessment.

Arm/Group Title	Tafasitamab (MOR00208) + Lenalidomide (LEN)
Arm/Group Description:	MOR00208: MOR00208 was administered via IV infusion at a dose of 12 mg/kg. For the first three cycles (Cycles 1 to 3) of the study each cycle consisted of a MOR00208 infusion on Day 1, Day 8, Day 15 and Day 22 of the cycle. Additionally, a loading dose was administered on Day 4 of Cycle 1. Thereafter MOR00208 was administered on a bi-weekly (every 14 days) basis with infusions on Day 1 and Day 15 of each 28-day cycle. LEN: Participants self-administered a starting dose of 25 mg oral LEN daily on Days 1-21 of each cycle, for up to 12 cycles in total. LEN dose could be modified in a de-escalating fashion or discontinued based upon clinical and laboratory findings. On days when both study drugs were given together, LEN was administered prior to MOR00208.
Overall Number of Participants Analyzed	81
Measure Type: Count of Participants; Unit of Measure: Participants
	81 100.0%

16. Secondary Outcome

Title	Severity of Treatment-emergent Adverse Events (TEAEs)
Description	Number of participants with Severity of TEAEs during MOR00208 and LEN combination therapy.
Time Frame	Approximately 6.5 years after first participant enrolled

Outcome Measure Data

Analysis Population Description

SAF:

The SAF includes all participants who received at least one dose of MOR00208 or LEN and had at least one post-baseline safety assessment.

Arm/Group Title	Tafasitamab (MOR00208) + Lenalidomide (LEN)
Arm/Group Description:	MOR00208: MOR00208 was administered via IV infusion at a dose of 12 mg/kg. For the first three cycles (Cycles 1 to 3) of the study each cycle consisted of a MOR00208 infusion on Day 1, Day 8, Day 15 and Day 22 of the cycle. Additionally, a loading dose was administered on Day 4 of Cycle 1. Thereafter MOR00208 was administered on a bi-weekly (every 14 days) basis with infusions on Day 1 and Day 15 of each 28-day cycle. LEN: Participants self-administered a starting dose of 25 mg oral LEN daily on Days 1-21 of each cycle, for up to 12 cycles in total. LEN dose could be modified in a de-escalating fashion or discontinued based upon clinical and laboratory findings. On days when both study drugs were given together, LEN was administered prior to MOR00208.
Overall Number of Participants Analyzed	81
Measure Type: Count of Participants; Unit of Measure: Participants
Severe	43 53.1%
Moderate	31 38.3%
Mild	6 7.4%
Missing	1 1.2%

Adverse Events

Time Frame	From first day of study drug administration through 30 days after last dose, up to maximum duration of 6.5 years approximately after first participant enrolled.
Adverse Event Reporting Description	All adverse events (AEs) (except non-serious AEs for screening failures) that occurred after the provision of informed consent and up to 30 days after last study drug administration was recorded in the eCRF and in the participant's medical records, whether or not they were considered by the investigator to be related to the study drug. Thereafter, only AEs assessed as related were collected at the end of the study.
Arm/Group Title	Treatment (MOR00208, Lenalidomide)
Arm/Group Description	MOR00208 was administered via intravenous Infusion, weekly (Cycle 1-3) of the study each cycle consisted of a MOR00208 infusion on Day 1, Day 8, Day 15 and Day 22 of the cycle. Additionally, a loading dose was administered on Day 4 of Cycle 1. Thereafter MOR00208 was administered on a bi-weekly (every 14 days) basis with infusions on Day 1 and Day 15 of each 28-day cycle, until disease progression or unacceptable toxicity or discontinuation due to any other reason. Lenalidomide (Revlimid®), PO, daily, on Days 1-21 of each cycle, for up to 12 cycles in total. LEN dose could be modified in a de-escalating fashion or discontinued based upon clinical and laboratory findings. Treatment with LEN was stopped in case of disease progression, or unacceptable toxicity, or discontinuation for any other reason. On days when both study drugs were given together, LEN was administered prior to tafasitamab.
All-Cause Mortality
	Treatment (MOR00208, Lenalidomide)
	Affected / at Risk (%)
Total	45/81 (55.56%)
Serious Adverse Events
	Treatment (MOR00208, Lenalidomide)
	Affected / at Risk (%)	# Events
Total	47/81 (58.02%)
Blood and lymphatic system disorders
Febrile neutropenia † 1	5/81 (6.17%)	5
Agranulocytosis † 1	1/81 (1.23%)	2
Cardiac disorders
Atrial fibrillation † 1	2/81 (2.47%)	2
Cardiac failure congestive † 1	2/81 (2.47%)	2
Myocardial ischaemia † 1	1/81 (1.23%)	1
Cardio-respiratory arrest † 1	1/81 (1.23%)	1
Gastrointestinal disorders
Diarrhoea † 1	1/81 (1.23%)	1
General disorders
Fatigue † 1	1/81 (1.23%)	1
Pyrexia † 1	1/81 (1.23%)	1
Sudden death † 1	1/81 (1.23%)	1
Hepatobiliary disorders
Biliary colic † 1	1/81 (1.23%)	1
Cholecystitis † 1	1/81 (1.23%)	2
Infections and infestations
Pneumonia † 1	7/81 (8.64%)	7
Bronchitis † 1	2/81 (2.47%)	2
Bronchopulmonary aspergillosis † 1	1/81 (1.23%)	2
Cytomegalovirus infection † 1	1/81 (1.23%)	1
Enterobacter bacteraemia † 1	1/81 (1.23%)	1
Escherichia bacteraemia † 1	1/81 (1.23%)	1
Febrile infection † 1	1/81 (1.23%)	1
Influenza † 1	1/81 (1.23%)	1
Klebsiella sepsis † 1	1/81 (1.23%)	1
Lower respiratory tract infection † 1	2/81 (2.47%)	4
Neutropenic sepsis † 1	1/81 (1.23%)	1
Parainfluenzae virus infection † 1	1/81 (1.23%)	1
Progressive multifocal leukoencephalopathy † 1	1/81 (1.23%)	1
Respiratory syncytial virus infection † 1	1/81 (1.23%)	1
Sepsis † 1	1/81 (1.23%)	2
Soft tissue infection † 1	1/81 (1.23%)	1
Streptococcal sepsis † 1	1/81 (1.23%)	1
Urinary tract infection † 1	1/81 (1.23%)	1
Urinary tract infection enterococcal † 1	1/81 (1.23%)	1
Varicella zoster virus infection † 1	1/81 (1.23%)	1
COVID-19 † 1	3/81 (3.70%)	3
COVID-19 pneumonia † 1	1/81 (1.23%)	1
Gastroenteritis rotavirus † 1	1/81 (1.23%)	1
Intervertebral discitis † 1	1/81 (1.23%)	1
Respiratory tract infection † 1	1/81 (1.23%)	1
Injury, poisoning and procedural complications
Femur fracture † 1	1/81 (1.23%)	1
Lower limb fracture † 1	1/81 (1.23%)	1
Wound complication † 1	1/81 (1.23%)	1
Musculoskeletal and connective tissue disorders
Arthritis † 1	1/81 (1.23%)	1
Muscular weakness † 1	1/81 (1.23%)	1
Osteonecrosis † 1	1/81 (1.23%)	1
Pathological fracture † 1	1/81 (1.23%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma † 1	2/81 (2.47%)	2
Tumour flare † 1	1/81 (1.23%)	1
Basal cell carcinoma † 1	2/81 (2.47%)	2
Bowen's disease † 1	1/81 (1.23%)	1
Breast cancer † 1	1/81 (1.23%)	1
Lung adenocarcinoma † 1	1/81 (1.23%)	1
Myelodysplastic syndrome † 1	1/81 (1.23%)	1
Prostate cancer † 1	1/81 (1.23%)	1
Myeloproliferative neoplasm † 1	1/81 (1.23%)	1
Nervous system disorders
Cerebrovascular accident † 1	1/81 (1.23%)	1
Cervicobrachial syndrome † 1	1/81 (1.23%)	1
Cognitive disorder † 1	1/81 (1.23%)	1
Facial paralysis † 1	1/81 (1.23%)	1
Sciatica † 1	1/81 (1.23%)	1
Transient global amnesia † 1	1/81 (1.23%)	1
Transient ischaemic attack † 1	1/81 (1.23%)	1
Renal and urinary disorders
Renal failure † 1	1/81 (1.23%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism † 1	3/81 (3.70%)	3
Chronic obstructive pulmonary disease † 1	1/81 (1.23%)	2
Dyspnoea † 1	2/81 (2.47%)	2
Respiratory failure † 1	1/81 (1.23%)	1
Vascular disorders
Deep vein thrombosis † 1	1/81 (1.23%)	1
Haematoma † 1	1/81 (1.23%)	1
1 Term from vocabulary, MedDRA 25.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Treatment (MOR00208, Lenalidomide)
	Affected / at Risk (%)	# Events
Total	75/81 (92.59%)
Blood and lymphatic system disorders
Neutropenia † 1	40/81 (49.38%)	215
Anaemia † 1	30/81 (37.04%)	74
Thrombocytopenia † 1	23/81 (28.40%)	71
Leukopenia † 1	10/81 (12.35%)	44
Febrile neutropenia † 1	5/81 (6.17%)	6
Lymphopenia † 1	5/81 (6.17%)	10
Gastrointestinal disorders
Diarrhoea † 1	30/81 (37.04%)	63
Constipation † 1	15/81 (18.52%)	21
Nausea † 1	12/81 (14.81%)	21
Vomiting † 1	12/81 (14.81%)	15
Abdominal pain † 1	8/81 (9.88%)	9
Abdominal pain upper † 1	6/81 (7.41%)	8
General disorders
Asthenia † 1	21/81 (25.93%)	39
Oedema peripheral † 1	20/81 (24.69%)	35
Pyrexia † 1	18/81 (22.22%)	39
Fatigue † 1	13/81 (16.05%)	24
Mucosal inflammation † 1	6/81 (7.41%)	9
Immune system disorders
Hypogammaglobulinaemia † 1	5/81 (6.17%)	5
Infections and infestations
Bronchitis † 1	12/81 (14.81%)	19
Nasopharyngitis † 1	8/81 (9.88%)	11
Respiratory tract infection † 1	9/81 (11.11%)	17
Upper respiratory tract infection † 1	8/81 (9.88%)	9
Urinary tract infection † 1	10/81 (12.35%)	15
Gastroenteritis † 1	6/81 (7.41%)	9
Rhinitis † 1	7/81 (8.64%)	7
Sinusitis † 1	6/81 (7.41%)	7
Injury, poisoning and procedural complications
Infusion related reaction † 1	5/81 (6.17%)	5
Investigations
C-reactive protein increased † 1	9/81 (11.11%)	12
Blood creatinine increased † 1	7/81 (8.64%)	17
Gamma-glutamyltransferase increased † 1	6/81 (7.41%)	9
Blood alkaline phosphatase increased † 1	5/81 (6.17%)	9
Metabolism and nutrition disorders
Decreased appetite † 1	18/81 (22.22%)	20
Hypokalaemia † 1	15/81 (18.52%)	28
Hypomagnesaemia † 1	8/81 (9.88%)	26
Hypocalcaemia † 1	5/81 (6.17%)	16
Hyperglycaemia † 1	5/81 (6.17%)	18
Musculoskeletal and connective tissue disorders
Back pain † 1	16/81 (19.75%)	19
Muscle spasms † 1	12/81 (14.81%)	16
Pain in extremity † 1	8/81 (9.88%)	913
Arthralgia † 1	6/81 (7.41%)	11
Nervous system disorders
Headache † 1	7/81 (8.64%)	19
Paraesthesia † 1	7/81 (8.64%)	7
Sciatica † 1	5/81 (6.17%)	8
Psychiatric disorders
Anxiety † 1	6/81 (7.41%)	10
Renal and urinary disorders
Dysuria † 1	5/81 (6.17%)	5
Respiratory, thoracic and mediastinal disorders
Cough † 1	24/81 (29.63%)	36
Dyspnoea † 1	10/81 (12.35%)	16
Oropharyngeal pain † 1	6/81 (7.41%)	6
Productive cough † 1	5/81 (6.17%)	5
Skin and subcutaneous tissue disorders
Pruritus † 1	8/81 (9.88%)	9
Rash † 1	8/81 (9.88%)	10
Rash maculo-papular † 1	5/81 (6.17%)	5
Vascular disorders
Hypertension † 1	7/81 (8.64%)	10
Hypotension † 1	6/81 (7.41%)	6
1 Term from vocabulary, MedDRA 25.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Lisa Walz
• Organization: MorphoSys AG
• Phone: +49 89 89927 26240
• EMail: Lisa.Walz@morphosys.com

Publications of Results:

Salles G, Duell J, Gonzalez Barca E, Tournilhac O, Jurczak W, Liberati AM, Nagy Z, Obr A, Gaidano G, Andre M, Kalakonda N, Dreyling M, Weirather J, Dirnberger-Hertweck M, Ambarkhane S, Fingerle-Rowson G, Maddocks K. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Lancet Oncol. 2020 Jul;21(7):978-988. doi: 10.1016/S1470-2045(20)30225-4. Epub 2020 Jun 5.

Duell J, Maddocks KJ, Gonzalez-Barca E, Jurczak W, Liberati AM, De Vos S, Nagy Z, Obr A, Gaidano G, Abrisqueta P, Kalakonda N, Andre M, Dreyling M, Menne T, Tournilhac O, Augustin M, Rosenwald A, Dirnberger-Hertweck M, Weirather J, Ambarkhane S, Salles G. Long-term outcomes from the Phase II L-MIND study of tafasitamab (MOR208) plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma. Haematologica. 2021 Sep 1;106(9):2417-2426. doi: 10.3324/haematol.2020.275958.

Duell J, Obr A, Augustin M, Endell J, Liu H, Geiger S, Silverman IM, Ambarkhane S, Rosenwald A. CD19 expression is maintained in DLBCL patients after treatment with tafasitamab plus lenalidomide in the L-MIND study. Leuk Lymphoma. 2022 Feb;63(2):468-472. doi: 10.1080/10428194.2021.1986219. Epub 2021 Nov 15. No abstract available.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Cherng HJ, Westin JR. Broadening the MIND: Tafasitamab and Lenalidomide versus Synthetic Controls. Clin Cancer Res. 2022 Sep 15;28(18):3908-3910. doi: 10.1158/1078-0432.CCR-22-1626.

Nowakowski GS, Yoon DH, Peters A, Mondello P, Joffe E, Fleury I, Greil R, Ku M, Marks R, Kim K, Zinzani PL, Trotman J, Huang D, Waltl EE, Winderlich M, Kurukulasuriya NC, Ambarkhane S, Hess G, Salles G. Improved Efficacy of Tafasitamab plus Lenalidomide versus Systemic Therapies for Relapsed/Refractory DLBCL: RE-MIND2, an Observational Retrospective Matched Cohort Study. Clin Cancer Res. 2022 Sep 15;28(18):4003-4017. doi: 10.1158/1078-0432.CCR-21-3648.

Zinzani PL, Rodgers T, Marino D, Frezzato M, Barbui AM, Castellino C, Meli E, Fowler NH, Salles G, Feinberg B, Kurukulasuriya NC, Tillmanns S, Parche S, Dey D, Fingerle-Rowson G, Ambarkhane S, Winderlich M, Nowakowski GS. RE-MIND: Comparing Tafasitamab + Lenalidomide (L-MIND) with a Real-world Lenalidomide Monotherapy Cohort in Relapsed or Refractory Diffuse Large B-cell Lymphoma. Clin Cancer Res. 2021 Nov 15;27(22):6124-6134. doi: 10.1158/1078-0432.CCR-21-1471. Epub 2021 Aug 25.

• Responsible Party: MorphoSys AG
• ClinicalTrials.gov Identifier: NCT02399085
• Other Study ID Numbers: MOR208C203; 2014-004688-19 ( EudraCT Number )
• First Submitted: March 13, 2015
• First Posted: March 26, 2015
• Results First Submitted: November 27, 2019
• Results First Posted: February 5, 2020
• Last Update Posted: October 23, 2023