A Study to Learn About the Effects of the Combination of Elranatamab, Daratumumab and Lenalidomide Compared With Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Who Are Not Candidates for Transplant

Официальное название

AN OPEN-LABEL, 2-ARM, MULTICENTER, RANDOMIZED PHASE 3 STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ELRANATAMAB (PF-06863135) + DARATUMUMAB + LENALIDOMIDE VERSUS DARATUMUMAB + BORTEZOMIB + LENALIDOMIDE + DEXAMETHASONE IN TRANSPLANT-INELIGIBLE PARTICIPANTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA

Обзор

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. The main purpose of the study is to evaluate if the combination of Elranatamab, Daratumumab and Lenalidomide offers superior clinical benefit compared with the combination of Daratumumab, Bortezomib, Lenalidomide and Dexamethasone in people with newly diagnosed multiple myeloma. There are 2 parts to this study. Part 1 will characterize the safety and tolerability of elranatamab in combination with daratumumab and lenalidomide or in combination with lenalidomide and will identify the optimal dose(s) of the combination regimen. Part 2 of the study will evaluate the rate of minimal residual disease (MRD) negative CR and the progression free survival (PFS) of the combination of elranatamab, daratumumab, and lenalidomide compared with the combination of daratumumab, bortezomib, lenalidomide, and dexamethasone in participants with newly diagnosed multiple myeloma.

Вмешательства

• Препарат Elranatamab
  Part 1 Dose Level 1 is not randomized. All other cohorts are randomized.
• Препарат Daratumumab
  Part 1 Dose Level 1 is not randomized. All other cohorts are randomized.
• Препарат Lenalidomide
  Part 1 Dose Level 1 is not randomized. All other cohorts are randomized.
• Препарат Dexamethasone
  Randomized
• Препарат Bortezomib
  Randomized

Первичные конечные точки

• Part 1 Dose Limiting Toxicity [Срок оценки: From the first dose of elranatamab/first full dose in combination with EDR until 28 days (+/- visit window) from the first administration of elranatamab with daratumumab and lenalidomide]
• Part 2: Progression free survival per IMWG [Срок оценки: From randomization up to 97 months.]
• Part 2: Minimal Residual Disease negative CR rate [Срок оценки: At 12 months after randomization]

Вторичные конечные точки (12)

• Overall Survival [Срок оценки: From date of randomization up to 97 months]
• Overall minimal residual disease negative CR rate [Срок оценки: From date of randomization up to 97 months]
• Sustained MRD negative CR rate (Part 2) [Срок оценки: From date of randomization up to 97 months]
• Duration of minimal residual disease negative CR (Part 2) [Срок оценки: From date of minimal residual disease negative CR status up to 97 months]
• PFS by investigator [Срок оценки: From date of randomization up to 97 months]
• PFS2 by investigator (Part 2) [Срок оценки: From the date of randomization up to 97 months]
• Objective Response Rate [Срок оценки: From the date of randomization up to 97 months]
• Complete Response Rate [Срок оценки: From the date of randomization up to 97 months]
• Time to Response [Срок оценки: From the date of randomization to date of confirmed objective response up to 97 months]
• Duration of Response [Срок оценки: From the date of confirmed objective response up to 97 months]
• Duration of Complete Response [Срок оценки: From the date of confirmed complete response up to 97 months]
• Frequency of treatment-emergent adverse events [Срок оценки: From the date of first dose of study intervention up to 97 months]

Критерии участия

Критерии включения

• Diagnosis of multiple myeloma (MM) as defined by IMWG criteria (Rajkumar et al., 2014)
• Measurable disease based on IMWG criteria as defined by at least 1 of the following:

• Serum M-protein ≥0.5 g/dL (Part 1) and ≥1 g/dL (Part 2);
• Urinary M-protein excretion ≥200 mg/24 hours;
• Involved FLC ≥10 mg/dL (≥100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FLC ratio (<0.26 or >1.65).
• Part 1: Participants with relapsed/refractory multiple myeloma (RRMM) who have received 1-2 prior lines of therapy including at least one immunomodulatory drug and one proteasome inhibitor: or participants with newly-diagnosed multiple myeloma (NDMM) that are transplant-ineligible as defined by age ≥65 years or transplant-ineligible as defined by age <65 years with comorbidities impacting the possibility of transplant.
• Part 2: participants with newly-diagnosed multiple myeloma that are transplant-ineligible defined as:

• Participants not considered candidates for high-dose chemotherapy and ASCT due to age or
• Participants with important comorbidities likely to have a negative impact on tolerability of high dose chemotherapy and ASCT.
• ECOG performance status ≤2.
• Not pregnant and willing to use contraception
• For participants with RRMM: Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1.

Критерии исключения

• Smoldering Multiple Myeloma.
• Monoclonal gammopathy of undetermined significance.
• Waldenströms Macroglobulinemia
• Plasma cell leukemia.
• Active, uncontrolled bacterial, fungal, or viral infection, including (but not limited to) COVID-19/SARS-CoV-2, HBV, HCV, and known HIV or AIDS-related illness.
• Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, carcinoma in situ, or Stage 0/1 with minimal risk of recurrence per investigator.
• For participants with RRMM: Previous treatment with a BCMA-directed therapy or anti-CD38-directed therapy within 6 months preceding the first dose of study intervention in this study. Stem cell transplant ≤3 months prior to first dose of study intervention or active GVHD.
• For participants with NDMM: Previous systemic treatment for MM except for a short course of corticosteroids (ie, total of 160 mg dexamethasone or equivalent before the first dose of study intervention). A cumulative dose of systemic corticosteroids equivalent to ≥20 mg of dexamethasone during screening.
• Live attenuated vaccine administered within 4 weeks of the first dose of study intervention.
• Administration of investigational product (eg, drug or vaccine) concurrent with study intervention or within 30 days (or as determined by the local requirement) preceding the first dose of study intervention used in this study.

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

Открытое

Основная цель

Лечение

Центры проведения

Испания · 15 центров

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Италия · 14 центров

• IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori- IRST S.r.l — Meldola (Fc)
• AUSL di Piacenza — Piacenza
• Ospedale Santa Maria delle Croci — Ravenna
• IRCCS Casa Sollievo della Sofferenza — San Giovanni Rotondo
• Cro-Irccs — Aviano
• Fondazione IRCCS San Gerardo dei Tintori — Monza
• Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino — Turin
• A.O.U. Policlinico Paolo Giaccone — Palermo
• … и ещё 6 центров

Китай · 12 центров

• Peking University Third Hospital — Пекин
• Fujian Medical University Union Hospital — Фучжоу
• Southern Medical University Nanfang Hospital — Гуанчжоу
• Sun Yat-sen University Cancer Center — Гуанчжоу
• Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology — Ухань
• Nanjing Drum Tower Hospital — Нанкин
• The First Affiliated Hospital of Soochow University — Сучжоу
• The first hospital of jilin university — Changchun
• … и ещё 4 центра

США · 10 центров

• Jupiter Medical Center/Anderson Family Cancer Institute — Jupiter
• MSK Basking Ridge — Basking Ridge
• MSK Monmouth — Middletown
• MSK Bergen — Montvale
• MSK Commack — Commack
• MSK Westchester — Harrison
• Memorial Sloan Kettering Cancer Center - David H. Koch Center for Cancer Care (74th Street — New York
• Memorial Sloan Kettering Cancer Center-Main Campus — New York
• … и ещё 2 центра

Япония · 10 центров

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South Korea · 6 центров

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Австралия · 5 центров

• Pindara Private Hospital — Benowa
• St Vincent's Hospital Melbourne — Fitzroy
• Epworth Freemasons — Melbourne
• The Alfred Hospital — Melbourne
• Epworth Healthcare — Richmond

Канада · 5 центров

• Cross Cancer Institute — Edmonton
• Dr. Everett Chalmers Regional Hospital — Fredericton
• QEII Health Sciences Centre — Halifax
• Nova Scotia Health Authority — Halifax
• Princess Margaret Cancer Centre — Toronto

Франция · 5 центров

• Centre Hospitalier Universitaire de Nice - Hôpital l'Archet — Nice
• Institut Universitaire du Cancer Toulouse - Oncopole - CHU de TOULOUSE — Toulouse
• Centre Hospitalier Universitaire de Poitiers — Poitiers
• Centre Hospitalier Universitaire de Nantes - L' Hopital l'hôtel-Dieu — Nantes
• Hôpital Saint Antoine — Paris

Германия · 5 центров

• Universitaetsklinikum Tuebingen — Tübingen
• Universitaetsklinikum Ulm — Ulm
• Universitätsmedizin Johannes Gutenberg Universität Mainz — Mainz
• Städtisches Klinikum Braunschweig — Braunschweig
• Klinikum Chemnitz — Chemnitz

Греция · 5 центров

• Evangelismos General Hospital of Athens — Athens
• Alexandra General Hospital of Athens — Athens
• "Theagenio" Cancer Hospital of Thessaloniki — Thessaloniki
• Evangelismos General Hospital of Athens — Athens
• University Hospital of Ioannina — Ioannina

Израиль · 5 центров

• Rabin Medical Center — Petah Tikva
• The Edmond and Lily Safra Children's Hospital; The Chaim Sheba Medical Center — Ramat Gan
• Hadassah Medical Center — Jerusalem
• Soroka Medical Center — Beersheba
• Sourasky Medical Center — Tel Aviv

Австрия · 4 центра

• Medizinische Universität Graz — Graz
• Landeskrankenhaus Feldkirch — Rankweil
• Uniklinikum Salzburg — Salzburg
• Medizinische Universität Wien — Vienna

Финляндия · 4 центра

• Kuopion Yliopistollinen Sairaala — Kuopio
• Turku University Hospital — Turku
• Helsinki University Hospital - Comprehensive Cancer Center (HYKS - Syöpäkeskus) — Helsinki
• Oulu University Hospital — Oulu

Тайвань · 4 центра

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Бельгия · 3 центра

• Clinique Saint Pierre — Ottignies
• Grand Hôpital de Charleroi — Gilly
• AZ Delta vzw — Roeselare

Чехия · 3 центра

• Fakultní nemocnice Brno Bohunice — Brno
• Fakultni nemocnice Olomouc — Olomouc
• Vseobecna fakultni nemocnice v Praze — Prague

Новая Зеландия · 3 центра

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Польша · 3 центра

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Великобритания · 2 центра

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Бразилия · 1 центр

• Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Pa — Ribeirão Preto

Нидерланды · 1 центр

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Пуэрто-Рико · 1 центр

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Швейцария · 1 центр

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Идентификаторы

NCT: NCT05623020 · C1071006 · MAGNETISMM-6 · 2024-514139-50-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗