To Evaluate the Efficacy and Safety of QL2109 and DARZALEX FASPRO® in Multiple Myeloma

Официальное название

A Randomized, Multicenter, Double-Blind, Parallel-Controlled, Phase III Clinical Study to Evaluate QL2109/ DARZALEX FASPRO® in Combination With Pomalidomide and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma Who Have Received at Least One Prior Line of Therapy With Both Lenalidomide and a Proteasome Inhibitor

Обзор

This is a randomized, double-blind, multicenter trial，parallel control designed to evaluate treatment with pomalidomide + QL2109 + dexamethasone compared with pomalidomide + DARZALEX FASPRO® + dexamethasone in the participants with relapsed or refractory Multiple Myeloma.

Вмешательства

• Препарат QL2109
  QL2109 will be given 1800 mg subcutaneously at weekly intervals (QW) for 8 weeks, then every 2 weeks (Q2W) for an additional 16 weeks, then every 4 weeks (Q4W) thereafter. Subjects will receive pre-infusion medications before infusions to mitigate potential IRRs.
• Препарат Pomalidomide
  Intervention Description：Pomalidomide will be administered at full dose of 4 mg orally (PO) on Days 1 through 21 of each 28-day cycle
• Препарат Dexamethasone
  Dexamethasone will be administered at a dose of 40 mg (20 mg for patients ≥75 years of age) orally, once daily on Days 1, 8, 15, and 22 of each 28-day treatment cycle
• Препарат DARZALEX FASPRO®
  DARZALEX FASPRO® will be given 1800 mg subcutaneously at weekly intervals (QW) for 8 weeks, then every 2 weeks (Q2W) for an additional 16 weeks, then every 4 weeks (Q4W) thereafter. Subjects will receive pre-infusion medications before infusions to mitigate potential IRRs

Первичные конечные точки

• Percentage of Participants With Very Good Partial Response (VGPR) or Better [Срок оценки: from baseline to week 24]

Вторичные конечные точки (3)

• Percentage of Participants With Very Good Partial Response (VGPR) or Better [Срок оценки: from baseline to week 12 and week 48]
• Overall Response Rate [Срок оценки: from baseline to week 24 and week 48]
• Overall survival at 18 months [Срок оценки: from baseline to 18 months]

Критерии участия

Критерии включения

• Males and females at least 18 years of age.
• Subject must have measurable disease of MM as defined by the criteria below:Serum M-protein level ≥0.5 g/dL or urine M-protein level ≥200 mg/24 hours; or Light chain multiple myeloma, for subjects without measurable disease in the serum or urine: Serum immunoglobulin free light chain (FLC) ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio.
• Subjects must have received prior antimyeloma treatment. The prior treatment must have included both a PI- and lenalidomide-containing regimens. Subjects who received only 1 line of prior treatment must have demonstrated PD on or within 60 days of completion of the lenalidomide containing regimen (ie, lenalidomide refractory).
• Subjects must have documented evidence of PD based on the investigator's determination of response as defined by the modified IMWG criteria on or after the last regimen.
• Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2.
• For subjects experiencing toxicities resulting from previous therapy, the toxicities must be resolved or stabilized to ≤Grade 1.
• Any of the following laboratory test results during Screening:

• Absolute neutrophil count ≥1.0 × 109/L;
• Hemoglobin level ≥75 g/L (≥4.65 mmol/L); (transfusions are not permitted to reach this level);
• Platelet count ≥75 × 109/L in subjects in whom <50% of bone marrow nucleated cells are plasma cells and platelet count ≥50 x 109/L in subjects in whom ≥50% of bone marrow nucleated cells are plasma cells;
• Alanine aminotransferase (ALT) level ≤2.5 times the upper limit of normal (ULN);Aspartate aminotransferase (AST) level ≤2.5 x ULN;
• Total bilirubin level ≤1.5 x ULN, (except for Gilbert Syndrome: direct bilirubin ≤1.5 × ULN);
• Creatinine clearance ≥30 mL/min
• Serum calcium corrected for albumin ≤14.0 mg/dL (≤3.5 mmol/L), or free ionized calcium ≤ 6.5 mg/dL (≤1.6 mmol/L).

Критерии исключения

• Subject has plasma cell leukemia (>2.0 × 109/L circulating plasma cells by standard differential) or Waldenström's macroglobulinemia or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or amyloidosis.
• History of malignancy (other than MM) within 3 years before the date of randomization (exceptions are squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other non-invasive lesion that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years).
• Clinical signs of meningeal involvement of MM.
• Previous therapy with any anti-CD38 monoclonal antibody.
• Previous exposure to pomalidomide.
• Subject has received antimyeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before the date of randomization. The only exception is emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 mg/day for a maximum of 4 days) for palliative treatment before Cycle 1, Day 1 (C1D1).
• Previous allogenic stem cell transplant; or autologous stem cell transplantation (ASCT) within 12 weeks before C1D1.
• Subject has had major surgery within 2 weeks before randomization, or has not fully recovered from an earlier surgery, or has surgery planned during the time the subject is expected to participate in the study or within 2 weeks after the last dose of study drug administration.
• Ongoing ≥ Grade 2 peripheral neuropathy.
• Subject had ≥Grade 3 rash during prior therapy.
• Pregnant or nursing women.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT06742138 · QL2109-301

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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