This is an open-label, multicenter study to evaluate safety and tolerability, determine the
RP2Ds of tafasitamab anlone in Japanese participants with NHL., or tafasitimab in combination
with lenalidomide in in Japanese participants with R/R DLBCL, or tafasitimab in combination
with parsaclisib in in Japanese participants with R/R DLBCL or tafasitimab in combination
with lenalidomide plus R-CHOP in Japanese participants with previously untreated DLBCL.
Inclusion Criteria:
- Groups 1 and 2 only: Biopsy-proven participants with relapsed or refractory NHL of
DLBCL, FL or MZL..
- Groups 3, and 4 only: Biopsy-proven participants with relapsed or refractory DLBCL..
- Groups 5 only: Biopsy-proven participants with relapsed or refractory DLBCL..
- 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
- Groups 1 and 2 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 3, 4a, and 4b 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: Participant must have: a. Untreated DLBCL. b. Ann Arbor Stage III to IV. c.
IPI status of 3 to 5 or age-adjusted IPI 2-3 (in Group 5 only). d. Appropriate candidate
for R-CHOP. e. LVEF of ≥ 50%, assessed by echocardiography.
-Willingness to avoid pregnancy or fathering children.
-In the opinion of investigator, the participant must: a. Not have a history of
noncompliance in relation to medical regimens or be considered potentially unreliable
and/or uncooperative.
b. 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
- Gastrointestinal abnormalities including the inability to take oral study treatment,
requiring IV alimentation, or prior surgical procedure affecting absorption.
- Pregnancy or lactation.
- Groups 3 and 5 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
- Groups 4a and 4b 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, 2, 3, 4a, and 4b only: Participants who have: a. Not discontinued
CD20-targeted therapy, chemotherapy, radiotherapy, investigational anticancer therapy,
or other lymphoma-specific therapy within the 14 days prior to Day 1 dosing.
b. In the opinion of the investigator, not recovered sufficiently from the adverse
toxic effects of prior therapies.
c. Previous treatment with CD19-targeted therapy (eg, CD19-CAR-T therapies, other CD19
mAbs including bispecific and ADCs).
d. Group 3 only: Been previously treated with IMiDs (eg, thalidomide or LEN). e. Group
4a and 4b only: Been previously treated with selective PI3Kδ or pan-PI3K inhibitors
(eg, idelalisib, copanlisib, duvelisib) and/or Bruton's tyrosine kinase inhibitors
(eg, ibrutinib).
f. 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).
g. 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.
h. Undergone previous allogenic stem cell transplantation. i. Concurrent treatment
other anticancer or experimental treatments.
- Group 5 only: Participants who have: a. A history of radiation therapy to ≥ 25% of the
bone marrow for other diseases or history of anthracycline therapy.
b. 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.
c. Contraindication to any of the individual components of R-CHOP. d. Any anticancer
and/or investigational therapy within 30 days prior to the start of Cycle 1, except
for permitted prephase treatment defined below.