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

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.

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.