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 LymphomaDiffuse Large B-cell Lymphoma
- Interventions
- Registration Number
- NCT04661007
- Lead Sponsor
- Incyte Biosciences Japan GK
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 65
- 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).
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Group 5 only: Participants must have:
- Untreated DLBCL.
- Ann Arbor Stage III to IV.
- IPI status of 3 to 5 or age-adjusted IPI 2-3 (in Group 5 only).
- Appropriate candidate for R-CHOP.
- LVEF of ≥ 50%, assessed by echocardiography.
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Willingness to avoid pregnancy or fathering children.
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In the opinion of investigator, the participant must:
- 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.
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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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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.
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Pregnancy or lactation.
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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
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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
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Groups 1, 3, 4a and 6 only: Participants who have:
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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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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.
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Groups 2, 3 and 6 only: Been previously treated with IMiDs (eg, thalidomide or LEN).
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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).
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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.
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Concurrent treatment other anticancer or experimental treatments.
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Group 5 only: Participants who have:
- A history of radiation therapy to ≥ 25% of the bone marrow for other diseases or history of anthracycline therapy.
- 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.
- Contraindication to any of the individual components of R-CHOP.
- Any anticancer and/or investigational therapy within 30 days prior to the start of Cycle 1, except for permitted prephase treatment defined below.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 2 : tafasitamab combination therapy R-CHOP 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. Modified tafasitamab dosing when combined with lenalidomide (Group 2) in participants with R/R DLBCL will be evaluated to determine the recommended clinical dose. The dose of tafasitamab will be based on the weight-based RP2D that is deemed safe and tolerable in Part 1. Part 1 : tafasitimab monotherapy tafasitamab 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 1 group (Group 1) to evaluate weight-based doses of tafasitamab. Part 2 : tafasitamab combination therapy tafasitamab 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. Modified tafasitamab dosing when combined with lenalidomide (Group 2) in participants with R/R DLBCL will be evaluated to determine the recommended clinical dose. The dose of tafasitamab will be based on the weight-based RP2D that is deemed safe and tolerable in Part 1. Part 2 : tafasitamab combination therapy lenalidomide 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. Modified tafasitamab dosing when combined with lenalidomide (Group 2) in participants with R/R DLBCL will be evaluated to determine the recommended clinical dose. The dose of tafasitamab will be based on the weight-based RP2D that is deemed safe and tolerable in Part 1. Part 3 : Dose Expansion of tafasitamab +parsaclisib tafasitamab tafasitamab in combination with parsaclisib will be further evaluated in Group 4b at RP2D determined in Part 2 Part 4: tafasitamab combination therapy tafasitamab tafasitamiab in combination with lenalidomide will be further evaluated in Group 6 at RP2D determined in Part 2. Part 4: tafasitamab combination therapy lenalidomide tafasitamiab in combination with lenalidomide will be further evaluated in Group 6 at RP2D determined in Part 2. Part 2 : tafasitamab combination therapy parsaclisib 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. Modified tafasitamab dosing when combined with lenalidomide (Group 2) in participants with R/R DLBCL will be evaluated to determine the recommended clinical dose. The dose of tafasitamab will be based on the weight-based RP2D that is deemed safe and tolerable in Part 1. Part 3 : Dose Expansion of tafasitamab +parsaclisib parsaclisib tafasitamab in combination with parsaclisib will be further evaluated in Group 4b at RP2D determined in Part 2
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
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: 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: 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
Trial Locations
- Locations (23)
Aichi Cancer Center Hospital
🇯🇵Aichi, Japan
Chiba Cancer Center
🇯🇵Chiba, Japan
National Cancer Center Hospital East
🇯🇵Chiba, Japan
National Hospital Organization Kyushu Cancer Center
🇯🇵Fukuoka, Japan
Kobe City Medical Center General Hospital
🇯🇵Hyogo, Japan
Tokai University Hospital
🇯🇵Kanagawa, Japan
The Cancer Institute Hospital of Jfcr
🇯🇵Koto-ku, Japan
Nho Shikoku Cancer Center
🇯🇵Matsuyama, Japan
Nho Kumamoto Medical Center
🇯🇵Kumamoto-ken, Japan
Tohoku University Hospital
🇯🇵Miyagi, Japan
Japanese Red Cross Nagoya Daini Hospital
🇯🇵Nagoya, Japan
Nho Hokkaido Cancer Center
🇯🇵Sapporo, Japan
Osaka University Hospital
🇯🇵Suita-shi, Japan
Nho Disaster Medical Center
🇯🇵Tachikawa, Japan
National Cancer Center Hospital
🇯🇵Tokyo, Japan
Mie University Hospital
🇯🇵TSU, Japan
Kindai University Hospital
🇯🇵Osakasayama City, Japan
University of Fukui Hospital
🇯🇵Fukui, Japan
Kyushu University Hospital
🇯🇵Fukuoka, Japan
Nho Okayama Medical Center
🇯🇵Okayama, Japan
Saitama Medical Center
🇯🇵Saitama-shi, Japan
Iuhw Narita Hospital
🇯🇵Narita City, Japan
Kanagawa Cancer Center
🇯🇵Yokohama-shi, Japan