NCT05972135招募中2 期
Outpatient Administration of Teclistamab or Talquetamab for Multiple Myeloma
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 30
- 主要终点
- Incidence of CRS of any grade during the first two cycles
研究概览
简要总结
This is a phase II study to evaluate the outpatient administration of Teclistamab or Talquetamab in Multiple Myeloma patients
详细描述
- This is a three-arm, non-randomized, multicenter, prospective study in adult patients with RRMM, who are administered Teclistamab (TECVAYLI™) or Talquetamab (TALVEY™), in the post-marketing setting.
- Teclistamab (TECVAYLI™) is a humanized IgG-4 PAA bispecific antibody designed to target the CD3 receptor complex on T cells and BCMA on B-lineage cells.
- Talquetamab (TALVEY™) is a humanized IgG-4 bispecific antibody designed to target the CD3 receptor complex on T cells and GPRC5D-expressing multiple myeloma (MM) cells This study will investigate the use of prophylactic tocilizumab or prophylactic dexamethasone to reduce the incidence and severity of CRS associated with teclistamab or talquetamab administration, to enable administration of the step-up dosing regimen of teclistamab or talquetamab in an outpatient setting.
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
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
- •Be ≥18 years of age (or the higher legal age in the jurisdiction in which the study is taking place) at the time of informed consent
- •Has documented diagnosis of MM according to the IMWG diagnostic criteria (Rajkumar 2011).
- •Teclistamab or Talquetamab + Tocilizumab: has received 2 or more prior MM therapies including a PI, IMiD and CD38 antibody.
- •Teclistamab + Oral Dexamethasone: has received 1 or more prior MM therapies including a PI, IMiD and/or CD38 antibody.
- •Teclistamab or Talquetamab + Tocilizumab: has an ECOG performance status (Oken 1982) of 0 to
- •Teclistamab + Oral Dexamethasone: has an ECOG performance status (Oken 1982) of 0 to
- •Measurable disease at screening, as assessed by local laboratory, defined by any of the following:
- •Serum M-protein level ≥0.5 g/dL; or
- •Urine M-protein level ≥200 mg/24 hours; or
- •Light chain MM without measurable M-protein in the serum or the urine: serum free light chain (sFLC) ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio.
- •For participants without measurable disease in the serum, urine, or involved FLC, presence of plasmacytomas (≥2 cm).
- •Human immunodeficiency virus-positive participants are eligible if they meet all of the following:
- •No detectable viral load (i.e., <50 copies/mL) at screening
- •CD4+ count >300 cells/mm3 at screening
- •No acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 6 months of screening
- •Receiving highly active antiretroviral therapy (HAART). Any changes in HAART due to resistance/progression should occur at least 3 months prior to enrollment. A change in HAART due to toxicity is allowed up to 4 weeks prior to enrollment.
- •Adequate organ system function
- •Body weight >35 kg.
- •A participant of childbearing potential must have a negative highly sensitive serum (β-hCG) at screening and within 72 hours of the start of study treatment and must agree to further serum or urine pregnancy tests during the study.
- •A participant must agree to abide by protocol defined contraceptive requirements for the duration of the study including avoiding donating gametes for specified period of time.
- •A participant must sign an ICF indicating that participant understands the purpose of, and procedures required for, the study and is willing to participate in the study.
- •A participant is required to stay within 60 minutes of transportation to the site and remain in the company of a competent adult at all times until 48 hours following administration of all doses within the teclistamab step-up dosing schedules
- •A participant is required to stay within 30 minutes of transportation to the site and remain in the company of a competent adult at all times until 48 hours following administration of all doses within the talquetamab step-up dosing schedule
- •A participant must agree to carry the study participant identification wallet card at all times.
- •A participant must comply with all the protocol requirement procedures, including measuring and recording of body temperature and blood oxygen saturation twice daily (≥8 hours apart) during the first 2 cycles of teclistamab or talquetamab treatment and coming to the study site for safety assessments.
- •A participant and the accompanying competent adult must be made aware of the presenting sign sand symptoms of teclistamab- or talquetamab- associated toxicities, including but not limited to CRS, ICANS, infections, etc. The accompanying competent adult must watch the participant at all times for teclistamab- or talquetamab- associated toxicities, until 48 hours after the first treatment dose of teclistamab or talquetamab.
排除标准
- •Has a rapidly progressing disease per investigator assessment.
- •Has plasma cell leukemia (>2.0×10^9/L plasma cells by standard differential), Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or primary amyloid light-chain amyloidosis.
- •Has known active CNS involvement or exhibits clinical signs of meningeal involvement of MM.
- •Has risk factors for developing clinically significant TLS and requiring management with increased hydration, allopurinol, or rasburicase.
- •Has myelodysplastic syndrome or active malignancies (ie, progressing or requiring treatment change in the last 12 months) other than RRMM. The only allowed exceptions are:
- •Any malignancy that was not progressing nor requiring treatment change in the last 12 months.
- •Malignancies treated within the last 12 months and considered at very low risk for recurrence:
- •Non-muscle invasive bladder cancer (solitary Ta-PUNLMP or low grade, <3 cm, no CIS).
- •Skin cancer (non-melanoma or melanoma).
- •Noninvasive cervical cancer.
- •Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ, localized breast cancer and receiving antihormonal agents.
- •Localized prostate cancer (M0, N0) with a Gleason Score ≤7a, treated locally only (RP/RT/focal treatment).
- •Other malignancy that is considered at minimal risk of recurrence.
- •Has Grade ≥3 hematologic AEs or Grade ≥3, clinically significant non-hematologic AEs.
- •Has fever or active infection (bacterial, viral, or uncontrolled systemic fungal) at time of study enrollment.
- •Has active autoimmune disease or a documented history of autoimmune disease with the exception of vitiligo, type I diabetes, and prior autoimmune thyroiditis that is currently euthyroid based on clinical symptoms and laboratory testing.
- •Has clinically significant coagulopathy that would increase the risk of bleeding in the setting of cytopenia.
- •Shows a deterioration in neurologic status, including mental status changes such as confusion or increased somnolence.
- •Has psychiatric disorders (eg, alcohol or drug abuse), dementia, or altered mental status that would compromise the ability to provide informed consent or comply with the clinical protocol.
- •History of stroke, transient ischemic attack or seizure within 6 months of signing ICF.
- •Presence of the following cardiac conditions:
- •New York Heart Association stage III or IV congestive heart failure.
- •Myocardial infarction or CABG ≤6 months prior to enrollment.
- •History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration.
- •History of severe non-ischemic cardiomyopathy.
- •Poorly controlled coronary artery disease and/or congestive heart failure.
- •Uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities.
- •Has hepatitis B infection (ie, HBsAg or HBV-DNA positive). In the event the infection status is unclear, quantitative viral levels are necessary to determine the infection status.
- •Has active hepatitis C infection as measured by positive HCV-RNA testing. Participants with a history of HCV antibody positivity must undergo HCV-RNA testing. If a participant with history of chronic hepatitis C infection (defined as both HCV antibody and HCV-RNA positive) completed antiviral therapy and has undetectable HCV-RNA 12 weeks following the completion of therapy, the participant is eligible for the study.
- •Has COPD with FEV1 <50% of predicted.
- •Has eGFR <20 ml/min or is dependent on dialysis.
- •Has other medical issue that would impair the ability of the participant to receive or tolerate the planned treatment at the investigational site, to understand informed consent or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
- •For talquetamab arm only: Prior Grade 3 or higher CRS related to any T-cell redirection (e.g., CD-3 redirection technology or CAR-T cell therapy), or any prior GPRC5D-targeting therapy.
- •Has received packed RBC or platelet transfusions within the last 7 days prior to dosing.
- •Has contraindications to the use of tocilizumab or IVIG per local prescribing information.
- •Has received live vaccine(s) within 1 month prior to screening or plans to receive live vaccines during the study.
- •Has received live, attenuated vaccine(s) within 30 days before the first dose of teclistamab or talquetamab. Live, attenuated influenza vaccines are permitted as late as 30 days before the study treatment.
- •Has received any non-anti-cancer investigational intervention or used any non-anti-cancer invasive investigational medical device within 21 days before the planned first dose of study treatment or received any non-anti-cancer investigational biological product within 21 days or 5 half-lives, whichever is shorter, before the planned study treatment, or is currently enrolled in an investigational study.
- •History of prior anti-cancer therapy as follows, before the first dose of study drug:
- •Targeted therapy, epigenetic therapy, or treatment with an investigational anti-cancer drug or used an invasive investigational medical device within 21 days or 5 half-lives, whichever is shorter.
- •Monoclonal antibody treatment for MM within 21 days.
- •Cytotoxic therapy within 21 days.
- •PI therapy within 14 days.
- •Immunomodulatory agent therapy within 7 days.
- •Radiotherapy within 14 days or focal radiation within 7 days.
- •For teclistamab arms only: Prior Gene modified adoptive cell therapy (eg, chimeric antigen receptor modified [CAR]-T cells, NK cells, or BCMA therapy)
- •For talquetamab arm only: Prior CAR-T or BCMA bispecific antibody therapy are allowed with the appropriate wash-out period: 1) Gene modified adoptive cell therapy (eg, chimeric antigen receptor modified [CAR]-T cells, NK cells) within 3 months, or 2) BCMA therapies (antibody-drug conjugates and bispecific antibodies, etc) within 21 days or at least 5 half-lives, whichever is less.
- •History of stem cell transplant:
- •An allogeneic stem cell transplant within 6 months. Participants who received an allogeneic transplant must be off all immunosuppressive medications for ≥42 days without signs of graft-versus-host disease.
- •An autologous stem cell transplant ≤12 weeks before the first dose of study drug.
研究组 & 干预措施
Teclistamab/Tocilizumab
Experimental
Participants will receive step up dosing of Teclistamab following the recommended dosage of TECVAYLI™ USPI followed by weekly dosing for twelve 28-day cycles, until disease progression, unacceptable toxicity, or the EOT (end of Cycle 12). Teclistamab dosing may be reduced to once every 2 weeks for participants who achieve partial response (PR) or better after 6 months of therapy.
干预措施: Teclistamab (Drug)
Talquetamab/Tocilizumab
Experimental
Participants will receive step up dosing of Talquetamab following the recommended dosage of TALVEY™ USPI followed by every 2 week dosing for six 28-day cycles, until disease progression, unacceptable toxicity, or the EOT (end of Cycle 6). Talquetamab dosing may be reduced to once every 4 weeks for participants who achieve very good partial response (VGPR) or better after Cycle 4. Participants in the talquetemab arm cannot be re-screened for or re-enrolled into the teclistamab arm.
干预措施: Tocilizumab (Drug)
Teclistamab/Tocilizumab
Experimental
Participants will receive step up dosing of Teclistamab following the recommended dosage of TECVAYLI™ USPI followed by weekly dosing for twelve 28-day cycles, until disease progression, unacceptable toxicity, or the EOT (end of Cycle 12). Teclistamab dosing may be reduced to once every 2 weeks for participants who achieve partial response (PR) or better after 6 months of therapy.
干预措施: Tocilizumab (Drug)
Talquetamab/Tocilizumab
Experimental
Participants will receive step up dosing of Talquetamab following the recommended dosage of TALVEY™ USPI followed by every 2 week dosing for six 28-day cycles, until disease progression, unacceptable toxicity, or the EOT (end of Cycle 6). Talquetamab dosing may be reduced to once every 4 weeks for participants who achieve very good partial response (VGPR) or better after Cycle 4. Participants in the talquetemab arm cannot be re-screened for or re-enrolled into the teclistamab arm.
干预措施: Talquetamab (Drug)
Teclistamab/Oral Dexamethasone
Experimental
Participants will receive step-up dosing of Teclistamab followed by weekly dosing for two cycles, every other week during Cycles 3-6 and once every 4 weeks from Cycles 7 through 12 until disease progression, unacceptable toxicity, or the EOT (end of Cycle 12). Teclistamab dosing may be reduced to once every 4 weeks for participants who achieve very good partial response (VGPR) or better starting with Cycle 3.
干预措施: Teclistamab (Drug)
Teclistamab/Oral Dexamethasone
Experimental
Participants will receive step-up dosing of Teclistamab followed by weekly dosing for two cycles, every other week during Cycles 3-6 and once every 4 weeks from Cycles 7 through 12 until disease progression, unacceptable toxicity, or the EOT (end of Cycle 12). Teclistamab dosing may be reduced to once every 4 weeks for participants who achieve very good partial response (VGPR) or better starting with Cycle 3.
干预措施: Oral Dexamethasone (Drug)
结局指标
主要结局
Incidence of CRS of any grade during the first two cycles
时间窗: From first dose of teclistamab or talquetamab, from Day 1 first step-up dose to the end of Cycle 2 (each cycle is 28 days)
Evaluate the overall incidence of CRS in the first 2 cycles after a single dose of prophylactic tocilizumab given 2 to 4 hours prior to step-up dose 1 of teclistamab or talquetamab or after 3 doses of oral dexamethasone given after each step-up dose and the first full dose of teclistamab.
次要结局
- Incidence of Grade ≥3 and any grade infections(Up to 12 months of teclistamab or 6 months for talquetamab treatment)
- Overall response rate (ORR)(Up to 12 months of teclistamab or 6 months for talquetamab treatment)
- Time to initial response (TTR)(Up to 12 months of teclistamab or 6 months for talquetamab treatment)
- Time to best response (TTBR)(Up to 12 months of teclistamab or 6 months for talquetamab treatment)
- Time to next treatment (TTNT)(Up to 12 months of teclistamab or 6 months for talquetamab treatment)
- Overall survival (OS)(Up to 12 months of teclistamab or 6 months for talquetamab treatment)
- Progression-free survival (PFS)(Day 1 of every 2 cycles From Cycle 1 Day 1 and up to approximately 12 months of teclistamab or 6 months for talquetamab treatment. (each cycle is 28 days)_)
- Talquetamab Arm only: Number of participants who have had a change in health-related quality of life parameters, from baseline to end of treatment(Up to 6 months for talquetamab treatment)
- Talquetamab Arm only: Number of participants with oral toxicities(Up to 6 months for talquetamab treatment)
- Talquetamab Arm only: Number of patients with overall side effects(Up to 6 months for talquetamab treatment)
- Talquetamab Arm only: Rate of treatment-emergent dysgeusia, oral mucositis, dysphagia, and xerostomia(Up to 6 months for talquetamab treatment)
- Talquetamab Arm only: Time to first onset of treatment-emergent dysgeusia, oral mucositis, dysphagia, and xerostomia(Up 6 to months for talquetamab treatment)
- Talquetamab Arm only: Duration of treatment-emergent dysgeusia, oral mucositis, dysphagia, and xerostomia(Up 6 to months for talquetamab treatment)
- Incidence of All grade and Grade ≥3 ICANS(From first dose of teclistamab or talquetamab, from Day 1 first step-up dose to the end of Cycle 2 (each cycle is 28 days))
- Incidence of All grade neutropenia and Grade ≥3 neutropenia(Up to 12 months of teclistamab or 6 months for talquetamab treatment)
- Incidence of all grade febrile neutropenia and Grade ≥3 febrile neutropenia(Up to 12 months of teclistamab or 6 months for talquetamab treatment)
- Total length of each hospital stay(Up to 12 months of teclistamab or 6 months for talquetamab treatment)
- Number of hospitalizations per participant(Up to 12 months of teclistamab or 6 months for talquetamab treatment)
- Healthcare resource utilization in the outpatient setting(From first dose of teclistamab or talquetamab, from Day 1 first step-up dose to the end of Cycle 2 (each cycle is 28 days))
- Timing of each hospital stay(Up to 12 months of teclistamab or 6 months for talquetamab treatment)
- Incidence of recurrent CRS of any grade(Up to 12 months of teclistamab or 6 months for talquetamab treatment)
- Incidence of CRS of any grade(Up to 12 months of teclistamab or 6 months for talquetamab treatment)
- Incidence of Grade ≥2 CRS(Up to 12 months of teclistamab or 6 months for talquetamab treatment)
- Incidence of Recurrent Grade ≥2 CRS(Up to 12 months of teclistamab or 6 months for talquetamab treatment)
- Incidence of All grade and Grade ≥3 neurotoxicity(From first dose of teclistamab or talquetamab, from Day 1 first step-up dose to the end of Cycle 2 (each cycle is 28 days))
- Incidence of recurrent CRS of any grade(From first dose of teclistamab or talquetamab, from Day 1 first step-up dose to the end of Cycle 2 (each cycle is 28 days))
- Incidence of Grade ≥2 CRS(From first dose of teclistamab or talquetamab, from Day 1 first step-up dose to the end of Cycle 2 (each cycle is 28 days))
- Incidence of Recurrent Grade ≥2 CRS(From first dose of teclistamab or talquetamab, from Day 1 first step-up dose to the end of Cycle 2 (each cycle is 28 days))
- Duration of response (DOR)(Day 1 of every 2 cycles from Cycle 1 Day 1 and up to approximately 12 months of teclistamab treatment or 6 months for talquetamab. (each cycle is 28 days))
研究者
研究点 (30)
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