to assess the safety and tolerability of tafasitamab alone or in combination with other drugs in japanese participants with non-hodgkins lymphoma (nhl)

Conditions: Non Hodgkins Lymphoma; Diffuse Large B-cell Lymphoma

Summary: 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 criteria:
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.

Keywords: incmor00208 tafasitamab