To Assess the Safety and Tolerability of Tafasitamab Alone or in Combination With Other Drugs in Japanese Participants With Non-Hodgkins Lymphoma (NHL)

• Status: Recruiting
• Trial end date: 2023-11-21
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Incyte Biosciences Japan GK
• Treatments: Lenalidomide

Criteria

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.