J-MIND: To Assess the Safety and Tolerability of Tafasitamab Alone or in Combination With Other Drugs in Japanese Participants With Non-Hodgkins Lymphoma (NHL)
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part 1 : tafasitimab monotherapy Dose-finding to evaluate the safety and tolerability and to determine the RP2Ds of single-agent tafasitamab in Japanese participants with NHL. Part 1 consists of 2 groups: Group 1 will evaluate weight-based doses of tafasitamab, and Group 2 will evaluate fixed doses of tafasitamab. |
Drug: tafasitamab
tafasitamab will be administered at protocol defined timepoints based on the groups participants are assigned.
Other Names:
|
| Experimental: Part 2 : tafasitamab combination therapy tafasitamab will be combined with lenalidomide (Group 3) or parsaclisib (Group 4a) in R/R DLBCL participants or lenalidomide plus R-CHOP (Group 5) in previously untreated DLBCL participants. The dose of tafasitamab will be based on the weight-based RP2D that is deemed safe and tolerable in Part 1. |
Drug: tafasitamab
tafasitamab will be administered at protocol defined timepoints based on the groups participants are assigned.
Other Names:
Drug: lenalidomide
lenalidomide will be administered orally at protocol defined timepoints based on the groups participants are assigned.
Drug: parsaclisib
parsaclisib will be administered at protocol defined timepoints based on the groups participants are assigned.
Drug: R-CHOP
R-CHOP is a combination regimen consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone. R-CHOP will be administered at protocol defined timepoints based on the groups participants are assigned.
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| Experimental: Part 3 : Dose Expansion of tafasitamab +parsaclisib tafasitamab in combination with parsaclisib will be further evaluated in Group 4b at RP2D determined in Part 2 |
Drug: tafasitamab
tafasitamab will be administered at protocol defined timepoints based on the groups participants are assigned.
Other Names:
Drug: parsaclisib
parsaclisib will be administered at protocol defined timepoints based on the groups participants are assigned.
|
Outcome Measures
Primary Outcome Measures
- Part 1,2 and 3 : Treatment Emergent Adverse Events (TEAE'S) [Approximately 2 years]
Adverse events reported for the first time or worsening of a pre-existing event after first dose of study treatment.
Secondary Outcome Measures
- Part 1,2, and 3 : Cmax of tafasitamab [Approximately 27 months]
Maximum observed serum concentration.
- Part 1, 2, and 3 : Cmin of tafasitamab [Approximately 27 months]
Minimum observed serum concentration over the dose interval.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Groups 1 and 2 only: Biopsy-proven participants with relapsed or refractory NHL of DLBCL, FL or MZL..
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Groups 3, and 4 only: Biopsy-proven participants with relapsed or refractory DLBCL..
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Groups 5 only: Biopsy-proven participants with relapsed or refractory DLBCL..
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Participants must have at least 1 bi-dimensionally measurable lesion.
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-ECOG performance status of 0 to 2.
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Participants with protocol defined laboratory criteria at screening
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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.
- 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
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History of prior non-hematologic malignancy
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Congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.
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Participants with known positive test result for hepatitis C, and hepatitis B.
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Known seropositive for or history of active viral infection with HIV.
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Known active bacterial, viral, fungal, mycobacterial, or other infection at screening.
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Known CNS lymphoma involvement - present or past medical history.
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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.
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History or evidence of rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.
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History or evidence of interstitial lung disease.
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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).
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Major surgery within up to 30 days prior to signing the ICF, unless the participant is recovered at the time of signing the ICF.
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Any anticancer and/or investigational therapy within 14 days prior to the start of Cycle 1
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Gastrointestinal abnormalities including the inability to take oral study treatment, requiring IV alimentation, or prior surgical procedure affecting absorption.
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Pregnancy or lactation.
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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
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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
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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.
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In the opinion of the investigator, not recovered sufficiently from the adverse toxic effects of prior therapies.
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Previous treatment with CD19-targeted therapy (eg, CD19-CAR-T therapies, other CD19 mAbs including bispecific and ADCs).
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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).
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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).
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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.
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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.
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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.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Aichi Cancer Center Hospital | Aichi | Japan | 464 8681 | |
| 2 | National Cancer Center Hospital East | Chiba | Japan | 277-8577 | |
| 3 | National Hospital Organization Kyushu Cancer Center | Fukuoka | Japan | 811-1395 | |
| 4 | Tohoku University Hospital | Sendai-shi | Japan | 908-8574 | |
| 5 | Osaka University Hospital | Suita-shi | Japan | 565-0871 | |
| 6 | National Cancer Center Hospital | Tokyo | Japan | 104-0045 |
Sponsors and Collaborators
- Incyte Biosciences Japan GK
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- INCMOR 0208-102