A PHASE 1/2, OPEN-LABEL, MULTICENTER STUDY TO EVALUATE A DOSING REGIMEN WITH TWO STEP-UP PRIMING DOSES AND LONGER DOSING INTERVALS OF ELRANATAMAB (PF-06863135) MONOTHERAPY IN PARTICIPANTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 86
- 试验地点
- 86
- 主要终点
- Number of Participants With Grade 2 or Higher Cytokine Release Syndrome (CRS) During Cycle 1: Parts 1 and 2
研究概览
简要总结
The purpose of the study (Part 1 and Part 2) is to evaluate the safety of a step-up dosing approach (starting with low doses followed by higher doses) of the study medicine (elranatamab) in participants with multiple myeloma that has come back after responding to treatment or has not responded to treatment (relapsed/refractory multiple myeloma). This study will also look at the safety and efficacy of different doses of elranatamab, as well as different intervals between doses.
Participants in the study will receive elranatamab as an injection under the skin at the study clinic. After the initial step-up doses, participants will start receiving one dose every week. The frequency of clinic visits for injections may then decrease over time. Participation will be at least two years.
详细描述
The purpose of the study (Part 1 and Part 2) of the study is to evaluate the safety (in particular the rate of Grade ≥ 2 CRS) of a step-up priming dose regimen of elranatamab in participants with relapsed/refractory multiple myeloma. In addition, this study will assess the safety of different dosing regimens of elranatamab and if it can provide a clinical benefit in those participants. Elranatamab is a bispecific antibody: binding of elranatamab to CD3-expressing T-cells and BCMA-expressing multiple myeloma cells causes targeted T-cell-mediated cytotoxicity.
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
- •Diagnosis of multiple myeloma (IMWG criteria, Rajkumar et al, 2014)
- •Measurable disease, as defined by at least 1 of the following:
- •Serum M-protein >0.5 g/dL by SPEP
- •Urinary M-protein excretion >200 mg/24 hours by UPEP
- •Serum immunoglobulin FLC≥10 mg/dL (≥100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FLC ratio
- •Refractory to at least one IMiD
- •Refractory to at least one PI
- •Refractory to at least one anti-CD38 antibody
- •Relapsed/refractory to last anti-myeloma regimen
- •ECOG performance status ≤1
- •Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1
- •Not pregnant and willing to use contraception
排除标准
- •Smoldering multiple myeloma
- •Active Plasma cell leukemia
- •POEMS syndrome
- •Amyloidosis
- •Waldenström's macroglobulinemia
- •Known active CNS involvement or clinical signs of myelomatous meningeal involvement
- •Stem cell transplant within 12 weeks prior to enrollment or active GVHD
- •Active HBV, HCV, SARS-CoV2, HIV, or any active, uncontrolled bacterial, fungal, or viral infection
- •Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ or Stage 0/1 malignancy with minimal risk of recurrence per investigator.
- •Previous treatment with an anti-BCMA bispecific antibody or CAR-T cell therapy.
- •Live attenuated vaccine within 4 weeks of the first dose
- •Previous administration with an investigational drug within 30 days or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer)
- •Known or suspected hypersensitivity to the study intervention, or any of its excipients
研究组 & 干预措施
Part 1
Evaluation of step-up priming dosing
干预措施: Elranatamab (Drug)
Part 2A
Dose determination
干预措施: Elranatamab (Drug)
Part 2B
Dose expansion
干预措施: Elranatamab (Drug)
Part 2C
To explore higher dose intensity
干预措施: Elranatamab (Drug)
结局指标
主要结局
Number of Participants With Grade 2 or Higher Cytokine Release Syndrome (CRS) During Cycle 1: Parts 1 and 2
时间窗: Parts 1 and 2: Cycle 1 (28 days)
CRS: supraphysiologic response following any immune therapy that results in the activation or engagement of endogenous or infused T-cells and/or other immune effector cells. Symptoms must include fever at the onset, and may include hypotension, hypoxia and end organ dysfunction. As per ASTCT criteria, Grade (G) 1: fever (temperature \>=38 degree Celsius), hypotension and/or hypoxia none; G 2: fever, hypotension not requiring vasopressors, hypoxia requiring low-flow nasal cannula/ facemask or blow-by; G 3: fever, hypotension requiring a vasopressor with or without vasopressin, hypoxia requiring high-flow nasal cannula/ facemask, nonrebreather mask, or Venturi mask; G 4: fever, hypotension requiring multiple vasopressors (excluding vasopressin), hypoxia requiring positive pressure. Organ toxicities associated with CRS graded according to CTCAE v5.0. G 1: Mild, G 2: Moderate, G 3: severe, and G 4: life-threatening consequences; urgent intervention indicated. G 5: death related to AE.
次要结局
- Number of Participants With Dose Limiting Toxicities (DLTs): Part 2A(Part 2A: 28 days starting from the first 116 or 152 mg dose)
- Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) [All Causalities and Treatment Related]: Parts 1 and 2(Day 1 of dosing up to 90 days post last dose (maximum treatment duration 25 cycles, follow up to 790 days))
- Number of Participants With Maximum Grade 3 or 4 and Grade 5 AEs [All Causalities and Treatment Related] Per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5: Parts 1 and 2(Day 1 of dosing up to 90 days post last dose (maximum treatment duration 25 cycles, follow up to 790 days))
- Number of Participants With Adverse Events of Special Interest (AESI)- CRS and Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS) [All Causalities and Treatment Related]: Parts 1 and 2(Day 1 of dosing up to 90 days post last dose (maximum treatment duration 25 cycles, follow up to 790 days))
- Number of Participants With Hematological Measures With Baseline CTCAE Grade >=2 Shifted to a Maximum CTCAE Grade 3-4: Parts 1 and 2(Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months))
- Number of Participants With Liver Function Tests Abnormalities: Parts 1 and 2(Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months))
- Time to Response (TTR) Per IMWG Response Criteria as Determined by Investigator: Parts 1 and 2(Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months))
- Minimal Residual Disease (MRD) Negativity Rate Per IMWG Sequencing Criteria: Parts 1 and 2(Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months))
- Pre- and Post-dose Concentrations of Elranatamab: Parts 1 and 2(Parts 1 and 2: Till study completion approximately 3 years 7 months)
- Number of Participants With Anti-Drug Antibody (ADA) and Neutralizing Antibody (Nab) Against Elranatamab: Parts 1 and 2(Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months))
- Number of Participants With Clinical Chemistry Parameters With Baseline CTCAE Grade >=2 Shifted to a Maximum CTCAE Grade 3-4: Parts 1 and 2(Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months))
- Objective Response Rate (ORR) Per International Myeloma Working Group (IMWG) Response Criteria as Determined by Investigator: Parts 1 and 2(Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months))
- Complete Response Rate (CRR) Per IMWG Response Criteria as Determined by Investigator: Parts 1 and 2(Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months))
- Duration of Response (DOR) Per IMWG Response Criteria as Determined by Investigator: Parts 1 and 2(Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months))
- Duration of Complete Response Rate (DOCR) Per IMWG Response Criteria as Determined by Investigator: Parts 1 and 2(Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months))
- Progression Free Survival (PFS) Per IMWG Response Criteria as Determined by Investigator: Parts 1 and 2(Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months))
- Overall Survival (OS): Parts 1 and 2(Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months))