Diffuse Large B-cell Lymphoma, Non Hodgkins Lymphoma
Conditions
Keywords
INCMOR00208, tafasitamab
Brief 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.
Interventions
DRUGtafasitamab
tafasitamab will be administered at protocol defined timepoints based on the groups participants are assigned.
DRUGlenalidomide
lenalidomide will be administered orally at protocol defined timepoints based on the groups participants are assigned.
DRUGparsaclisib
parsaclisib will be administered at protocol defined timepoints based on the groups participants are assigned.
DRUGR-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.
Sponsors
Incyte Biosciences Japan GK
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open Label
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Part 4: Objective Response | Approximately 27 months | Best Response of complete/complete metabolic response or partial/partial metabolic response |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1,2, 3 and 4 : Cmax of tafasitamab | Approximately 27 months | Maximum observed serum concentration. |
| Part 1, 2, 3 and 4: Cmin of tafasitamab | Approximately 27 months | Minimum observed serum concentration over the dose interval. |
| Part 4: Complete Response | Approximately 27 months | Defined as the proportion of participants with Complete Response as determined by an IRC and investigator assessment according to the Lugano criteria |
| Part 4: Duration of Response | Approximately 27 months | Defined as the time from the date of first documented evidence of CR or PR until the first documented disease progression or death from any cause, whichever occurs first, among participants who achieve an objective response as determined by IRC and investigator assessment based on the Lugano criteria for response assessment |
| Part 4: Progression-Free Survival | Approximately 27 months | Defined as the time from the date of randomization until the first documented disease progression as determined by IRC and investigator assessment based on the Lugano criteria for response assessment or death from any cause, whichever occurs first. |
| Part 4: Overall Survival | Approximately 27 months | Defined as the time from the date of randomization until death from any cause. |
| Part 4: Overall Response Rate | Approximately 27 months | Defined as the proportion of participants with a CR or PR as determined by the investigator based on the Lugano criteria for response assessment |
| Part 4: 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. |
Countries
Japan
Outcome results
None listed