A Phase 1b/2 Study of Tafasitamab, Tafasitamab Plus Lenalidomide, Tafasitamab Plus Parsaclisib, and Tafasitamab Plus Lenalidomide in Combination With R-CHOP in Japanese Participants With Non-Hodgkin Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 72
- 试验地点
- 46
- 主要终点
- Part 1,2 and 3 : Treatment Emergent Adverse Events (TEAE'S)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Open Label
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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:
- •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.
- •Willingness to avoid pregnancy or fathering children.
- •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.
排除标准
- •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
- •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:
- •Not discontinued CD20-targeted therapy, chemotherapy, radiotherapy, investigational anticancer therapy, or other lymphoma-specific therapy within the 14 days prior to Day 1 dosing.
- •In the opinion of the investigator, not recovered sufficiently from the adverse toxic effects of prior therapies.
- •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.
- •Groups 2, 3 and 6 only: Been previously treated with IMiDs (eg, thalidomide or LEN).
- •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).
- •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).
- •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.
- •Undergone previous allogenic stem cell transplantation.
- •Concurrent treatment other anticancer or experimental treatments.
- •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.
研究组 & 干预措施
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
干预措施: tafasitamab (Drug)
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. 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.
干预措施: R-CHOP (Drug)
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 1 group (Group 1) to evaluate weight-based doses of tafasitamab.
干预措施: tafasitamab (Drug)
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. 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.
干预措施: tafasitamab (Drug)
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. 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.
干预措施: lenalidomide (Drug)
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. 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.
干预措施: parsaclisib (Drug)
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
干预措施: parsaclisib (Drug)
Part 4: tafasitamab combination therapy
tafasitamiab in combination with lenalidomide will be further evaluated in Group 6 at RP2D determined in Part 2.
干预措施: tafasitamab (Drug)
Part 4: tafasitamab combination therapy
tafasitamiab in combination with lenalidomide will be further evaluated in Group 6 at RP2D determined in Part 2.
干预措施: lenalidomide (Drug)
结局指标
主要结局
Part 1,2 and 3 : Treatment Emergent Adverse Events (TEAE'S)
时间窗: 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
时间窗: Approximately 27 months
Best Response of complete/complete metabolic response or partial/partial metabolic response
次要结局
- Part 4: Treatment Emergent Adverse Events (TEAE'S)(Approximately 2 years)
- Part 1,2, 3 and 4 : Cmax of tafasitamab(Approximately 27 months)
- Part 1, 2, 3 and 4: Cmin of tafasitamab(Approximately 27 months)
- Part 4: Complete Response(Approximately 27 months)
- Part 4: Progression-Free Survival(Approximately 27 months)
- Part 4: Overall Survival(Approximately 27 months)
- Part 4: Overall Response Rate(Approximately 27 months)
- Part 4: Duration of Response(Approximately 27 months)