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

Study Overview
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Brief Summary
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This is a Phase II, Single-Arm, Open-Label, Multicentre Study to Evaluate the Safety and Efficacy of Lenalidomide Combined with MOR00208 in Participants with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R-R DLBCL).

Detailed Description
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The aim of this single-arm, multicentre, open-label Phase II study is to evaluate the Lenalidomide (LEN) combined with Tafasitamab (MOR00208) in adult participants with DLBCL who had relapsed after or were refractory to at least one, but no more than three previous systemic regimens administered for the treatment of their DLBCL and who were not candidates for high-dose chemotherapy and subsequent Autologous stem cell transplants and were thus considered to have exhausted their therapeutic options. One prior therapy line had to include an anti-CD20 targeted therapy (e.g., rituximab [RTX]). MOR00208 and LEN were administered for up to 12 cycles (28 days each), followed by MOR00208 monotherapy until progression, in participants with at least stable disease or a better response.

Official Title
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A Phase II, Single-Arm, Open-Label, Multicentre Study to Evaluate the Safety and Efficacy of Lenalidomide Combined With MOR00208 in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R-R DLBCL)

Conditions
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Diffuse Large B-cell Lymphoma

Intervention / Treatment
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* Drug: Tafasitamab
* Drug: Lenalidomide


Participation Criteria
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Eligibility Criteria
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Major Inclusion Criteria: Age >18 years Histologically confirmed diagnosis of DLBCL Tumour tissue for central pathology review and correlative studies had to be provided. Participants must had: relapsed and/or refractory disease at least one bidimensionally measurable, PET positive disease site (transverse diameter of ≥1.5 cm and perpendicular diameter of ≥1.0 cm at baseline) received at least one, but no more than three previous systemic regimens for the treatment of DLBCL and one therapy line must had included a CD20-targeted therapy Eastern Cooperative Oncology Group 0 to 2 Participants were not considered in the opinion of the investigator eligible, or participants unwilling to undergo intensive salvage therapy including ASCT Participants had to meet the following laboratory criteria at screening: absolute neutrophil count ≥1.5 × 10˄9/L platelet count ≥90 × 10˄9/L total serum bilirubin ≤2.5 × ULN or ≤5 × ULN in cases of Glibert's Syndrome or liver involvement by lymphoma alanine transaminase, aspartate aminotransferase and alkaline phosphatase ≤3 × ULN or <5 × ULN in cases of liver involvement serum creatinine clearance ≥60 mL/minute Females of childbearing potential (FCBP) must: not be pregnant refrain from breastfeeding and donating blood or oocytes agreed to ongoing pregnancy testing committed to continued abstinence from heterosexual intercourse, or agree to use and be able to comply with the use of double-barrier contraception Males (if sexually active with a FCBP) had to use an effective barrier method of contraception refrain from donating blood or sperm In the opinion of the investigator the participants had to: be able and willing to receive adequate prophylaxis and/or therapy for thromboembolic events be able to understand, give written informed consent and comply with all study-related procedures, medication use, and evaluations had no history of noncompliance in relation to medical regimens or not be considered potentially unreliable and/or uncooperative be able to understand the reason for complying with the special conditions of the pregnancy prevention risk management plan and gave written acknowledgement of this. Major Exclusion Criteria: Participants who had: other histological type of lymphoma primary refractory DLBCL a history of double/triple hit genetics Participants who had, within 14 days prior to Day 1 dosing: not discontinued CD20-targeted therapy, chemotherapy, radiotherapy, investigational anticancer therapy or other lymphoma specific therapy underwent major surgery or suffered from significant traumatic injury received live vaccines. required parenteral antimicrobial therapy for active, intercurrent infections Participants who: had, in the opinion of the investigator, not recovered sufficiently from the adverse toxic effects of prior therapies were previously treated with CD19-targeted therapy or immunomodulatory drugs (IMiDs)® (e.g., thalidomide, LEN) had a history of hypersensitivity to compounds of similar biological or chemical composition to MOR00208, IMiDs® and/or the excipients contained in the study drug formulations had undergone ASCT within the period ≤ 3 months prior to the signing of the Informed Consent Form. Patients who had a more distant history of ASCT had to exhibit full haematological recovery before enrolment into the study had undergone previous allogenic stem cell transplantation had a history of deep venous thrombosis/embolism, threatening thromboembolism or known thrombophilia or were at a high risk for a thromboembolic event in the opinion of the investigator and who were not willing/able to take venous thromboembolic event prophylaxis during the entire treatment period concurrently used other anti-cancer or experimental treatments Prior history of malignancies other than DLBCL, unless the participant had been free of the disease for ≥5 years prior to screening. Participants with: positive hepatitis B and/or C serology. known seropositivity for or history of active viral infection with human immunodeficiency virus (HIV) CNS lymphoma involvement history or evidence of clinically significant cardiovascular, CNS and/or other systemic disease that would in the investigator's opinion preclude participation in the study or compromised the participant's ability to give informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tafasitamab (MOR00208) + lenalidomide (LEN)<br>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. | Drug: Tafasitamab<br>* 12 mg/kg<br>* Other names: MOR00208;Drug: Lenalidomide<br>* 25 mg<br>* Other names: Revlimid®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Best Objective Response Rate (ORR) | 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. | Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DoR) by IRC Evaluation | DoR [months] = (date of assessment of tumor progression or death - date of assessment of first documented response of (CR or PR) + 1)/30.4375. | Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled | 
| DoR by Investigator (INV) Evaluation | DoR [months] = (date of assessment of tumour progression or death - date of assessment of first documented response of (CR or PR) + 1)/30.4375. | Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled | 
| Progression-free Survival (PFS) by IRC Evaluation | 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. | Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled | 
| PFS by INV Evaluation | 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. | Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled | 
| Overall Survival (OS) | 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). | Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled | 
| Disease Control Rate (DCR) by IRC Evaluation | 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. | Approximately 2.5 years after first participant enrolled | 
| DCR by INV Evaluation | 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. | Approximately 2.5 years after first participant enrolled | 
| Time to Progression (TTP) by IRC Evaluation | 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. | Approximately 2.5 years after first participant enrolled | 
| TTP by INV Evaluation | 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. | Approximately 2.5 years after first participant enrolled | 
| Time to Next Treatment (TTNT) | 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. | Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled | 
| Event-free Survival (EFS) by IRC Evaluation | 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. | Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled | 
| Serum Drug Levels of MOR00208 | 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). | 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 | 
| Number of Participants Who Developed Anti-MOR00208 Antibodies | 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). | Baseline, Up to a maximum of 23 cycles. | 
| Number of Participants That Experienced Treatment-emergent Adverse Events (TEAEs) | 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. | Approximately 6.5 years after first participant enrolled | 
| Severity of Treatment-emergent Adverse Events (TEAEs) | Number of participants with Severity of TEAEs during MOR00208 and LEN combination therapy. | Approximately 6.5 years after first participant enrolled | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DLBCL, Efficacy, MOR00208, Tafasitamab, lenalidomide