Overview

This is an open-label, multicenter study to evaluate safety and tolerability, determine the RP2Ds of tafasitamab alone in Japanese participants with R/R NHL, or to evaluate efficacy and safety of tafasitamab in combination with lenalidomide in Japanese participants with R/R DLBCL, or tafasitimab in combination with lenalidomide plus R-CHOP in Japanese participants with previously untreated DLBC, or tafasitimab in combination with lenalidomide in Japanese participants with previously R/R DLBC.

Eligibility

Inclusion Criteria:

• Group 1 only: Biopsy-proven participants with relapsed or refractory NHL of DLBCL, FL or MZL.
• Groups 3, 4a and 5 only: Biopsy-proven participants with relapsed or refractory DLBCL.
• Groups 2 and 6 only: Biopsy-proven participants with DLBCL and another select lymphoid neoplasms.
• Participants must have at least 1 bi-dimensionally measurable lesion.
• ECOG performance status of 0 to 2.
• Participants with protocol defined laboratory criteria at screening as defined in the protocol.
• Group 1 only:

        Received at least 1 previous systemic therapy line for the treatment of NHL. At least 1
        previous therapy line must have included a CD20-targeted therapy (eg, RTX).
          -  Groups 2, 3, 4a and 6 only:
        Received at least 1, but no more than 3, previous systemic therapy lines for the treatment
        of DLBCL. At least 1 previous therapy line must have included a CD20-targeted therapy (eg,
        RTX).
          -  Group 5 only: Participants must have:
               1. Untreated DLBCL.
               2. Ann Arbor Stage III to IV.
               3. IPI status of 3 to 5 or age-adjusted IPI 2-3 (in Group 5 only).
               4. Appropriate candidate for R-CHOP.
               5. LVEF of ≥ 50%, assessed by echocardiography.
          -  Willingness to avoid pregnancy or fathering children.
          -  In the opinion of investigator, the participant must:
               1. Not have a history of noncompliance in relation to medical regimens or be
                  considered potentially unreliable and/or uncooperative.
               2. Be able to understand the reason for complying with the special conditions of the
                  pregnancy prevention risk management plan and give written acknowledgement of
                  this.
        Exclusion Criteria:
          -  Any other histological type of lymphoma.
          -  History of prior non-hematologic malignancy.
          -  Congestive heart failure requiring use of ongoing maintenance therapy for
             life-threatening ventricular arrhythmias.
          -  Participants with known positive test result for hepatitis C, and hepatitis B.
          -  Known seropositive for or history of active viral infection with HIV.
          -  Known active bacterial, viral, fungal, mycobacterial, or other infection at screening.
          -  Known CNS lymphoma involvement - present or past medical history.
          -  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 compromise the participant's ability to give informed consent.
          -  History or evidence of rare hereditary problems of galactose intolerance, Lapp lactase
             deficiency or glucose-galactose malabsorption.
          -  History or evidence of interstitial lung disease.
          -  Vaccination with live vaccine within 21 days prior to study treatment (Note:
             throughout the study treatment period and at least 6 months after end of treatment,
             vaccination with live vaccines should be avoided).
          -  Major surgery within up to 30 days prior to signing the ICF, unless the participant is
             recovered at the time of signing the ICF.
          -  Any anticancer and/or investigational therapy within 14 days prior to the start of
             Cycle 1.
          -  Groups 2, 3, 4a, 5 and 6 only: Gastrointestinal abnormalities including the inability
             to take oral study treatment, requiring IV alimentation, or prior surgical procedure
             affecting absorption.
          -  Pregnancy or lactation.
          -  Groups 2, 3, 5 and 6 only: Participants who have history of deep venous
             thrombosis/embolism, threatening thromboembolism, stroke or known thrombophilia or are
             at a high risk for a thromboembolic event in the opinion of the investigator and who
             are not willing/able to take venous thromboembolic event prophylaxis during the entire
             treatment period if required
          -  Group 4a only: Use or expected use during the study of any restricted medications,
             including potent CYP3A4 inhibitors or inducers within 14 days or 5 half-lives
             (whichever is longer) before the date of study treatment administration
          -  Groups 1, 3, 4a and 6 only: Participants who have:
               1. Not discontinued CD20-targeted therapy, chemotherapy, radiotherapy,
                  investigational anticancer therapy, or other lymphoma-specific therapy within the
                  14 days prior to Day 1 dosing.
               2. In the opinion of the investigator, not recovered sufficiently from the adverse
                  toxic effects of prior therapies.
               3. Groups 1, 3 and 4a only: Previous treatment with CD19-targeted therapy (eg,
                  CD19-CAR-T therapies, other CD19 mAbs including bispecific and ADCs).
                  Groups 2 and 6 only: Previous treatment with tafasitamab. Note: Participants in
                  Groups 2 and 6 who have received previous CD19 directed therapy (other than
                  tafasitamab) must have CD19-positive lymphoma confirmed by a biopsy taken after
                  completing the prior CD19-targeted therapy.
               4. Groups 2, 3 and 6 only: Been previously treated with IMiDs (eg, thalidomide or
                  LEN).
               5. Group 4a only: Been previously treated with selective PI3Kδ or pan-PI3K
                  inhibitors (eg, idelalisib, copanlisib, duvelisib) and/or Bruton's tyrosine
                  kinase inhibitors (eg, ibrutinib).
               6. A history of hypersensitivity to compounds of similar biological or chemical
                  composition to tafasitamab, IMiDs, and/or the excipients contained in the study
                  treatment formulations (citric acid monohydrate, polysorbate 20, sodium citrate
                  dehydrate and trehalose dihydrate).
               7. Undergone ASCT within the period ≤ 3 months before the signing of the ICF.
                  Participants who have a more distant history of ASCT must exhibit full
                  hematological recovery before enrolment into the study.
               8. Undergone previous allogenic stem cell transplantation.
               9. Concurrent treatment other anticancer or experimental treatments.
          -  Group 5 only: Participants who have:
               1. A history of radiation therapy to ≥ 25% of the bone marrow for other diseases or
                  history of anthracycline therapy.
               2. A history of hypersensitivity or contraindication to any component of R-CHOP,
                  LEN, or compounds of similar biological or chemical composition as tafasitamab
                  and/or the excipients contained in the study treatment formulations or R-CHOP.
               3. Contraindication to any of the individual components of R-CHOP.
               4. Any anticancer and/or investigational therapy within 30 days prior to the start
                  of Cycle 1, except for permitted prephase treatment defined below.