Phase 1/2 Study of Linvoseltamab in Adult Patients With Relapsed or Refractory Multiple Myeloma

Официальное название

Phase 1/2 FIH Study of REGN5458 (Anti-BCMA x Anti-CD3 Bispecific Antibody) in Patients With Relapsed or Refractory Multiple Myeloma

Обзор

The main purpose of this study is to learn about the safety of linvoseltamab and to find out what is the best dose of linvoseltamab to give to patients with multiple myeloma and to look for any signs that linvoseltamab can effectively treat cancer. The study is looking at several other research questions, including: * Side effects that may be experienced by people receiving linvoseltamab * How linvoseltamab works in the body * How much linvoseltamab is present in the blood * How linvoseltamab may work to treat cancer

Вмешательства

• Препарат Linvoseltamab
  Administered per the protocol

Первичные конечные точки

• Incidence of dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period [Срок оценки: Up to 28 days]
• Incidence and severity of treatment-emergent adverse events (TEAEs) [Срок оценки: Up to 5 years]
• Incidence and severity of adverse events of special interest (AESI) [Срок оценки: Up to 5 years]
• Assessment of the pharmacokinetics (PK) of linvoseltamab [Срок оценки: Up to 5 years]
• Concentrations of linvoseltamab in serum over time [Срок оценки: Up to 5 years]
• Objective response rate (ORR) as determined by an Independent Review Committee (IRC) [Срок оценки: Up to 5 years]
• Incidence and severity of cytokine release syndrome (CRS) with linvoseltamab [Срок оценки: Up to 5 years]
• ORR of IV linvoseltamab as assessed by investigator [Срок оценки: Up to 5 years]

Вторичные конечные точки (12)

• Concentrations of linvoseltamab in the serum over time [Срок оценки: Up to 5 years]
• Incidence over time of anti-drug antibodies (ADAs) to linvoseltamab [Срок оценки: Up to 5 years]
• Titer of anti-drug antibodies (ADAs) to linvoseltamab over time [Срок оценки: Up to 5 years]
• Incidence of neutralizing antibodies (NAb) to linvoseltamab over time [Срок оценки: Up to 5 years]
• Duration of response (DOR) as determined by an IRC, measured using the IMWG criteria [Срок оценки: Up to 5 years]
• DOR as determined by an investigator, measured using the International Myeloma Working Group (IMWG) criteria [Срок оценки: Up to 5 years]
• Progression-free survival (PFS) as determined by an IRC, measured using the IMWG criteria [Срок оценки: Up to 5 years]
• PFS as determined by an investigator, measured using the IMWG criteria [Срок оценки: Up to 5 years]
• Rate of minimal residual disease (MRD) negative status, using the IMWG criteria [Срок оценки: Up to 5 years]
• Rate of MRD negative status [Срок оценки: Up to 5 years]
• Overall survival (OS) [Срок оценки: Up to 5 years]
• ORR as measured as determined by blinded IRC, as measured using the IMWG criteria [Срок оценки: Up to 5 years]

Критерии участия

Критерии включения

• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
• Confirmed diagnosis of active Multiple Myeloma (MM) by International Myeloma Working Group (IMWG) diagnostic criteria
• Patients must have myeloma that is response-evaluable according to the 2016 IMWG response criteria as defined in the protocol.

• Phase 1, Part 1 (Dose Escalation): Patients with MM who have exhausted all therapeutic options that are expected to provide meaningful clinical benefit, either through disease relapse, treatment refractory disease or intolerance of the therapy and including either:

a. Progression on or after at least 3 lines of therapy, or intolerance of therapy, including a proteasome inhibitor, an Immunomodulatory agent (IMiD), and an anti-CD38 antibody, OR b. Progression on or after an anti-CD38 antibody and have disease that is "double refractory" to a proteasome inhibitor and an IMiD, or intolerance of therapy. The anti-CD38 antibody may have been administered alone or in combination with another agent such as a proteasome inhibitor (PI). Refractory disease is defined as lack of response or relapse within 60 days of last treatment.

• Phase 1, Part 2 (SC Administration): Patients with MM whose disease meets the following criteria:

a. Progression on or after at least 3 prior lines of therapy including a(n) PI, IMiD, and anti-CD38 antibody, OR b. Patients must be triple-refractory, defined as being refractory to prior treatment with at least 1 anti-CD38 antibody, a proteasome inhibitor, and an IMiD.

• Phase 2 (Cohorts 1 and 2):

Patients with MM whose disease meets the following criteria:

a. Progression on or after at least 3 prior lines of therapy including a(n) PI, IMiD, and anti-CD38 antibody, OR b. Patients must be triple- refractory, defined as being refractory\* to prior treatment with at least 1 PI, 1 IMiD, and an anti-CD38 antibody.

• Phase 2 (Cohort 3):

Patients with MM whose disease meets the following criteria:

• Progression on or after at least 3 prior lines of therapy including a(n) PI, IMiD, and anti-CD38 antibody, OR
• Patients must be triple- refractory, defined as being refractory\* to prior treatment with at least 1 PI, 1 IMiD, and an anti-CD38 antibody.

• Refractory disease is defined as progression during treatment or within 60 days after completion of therapy, or <25% response to therapy.

AND, for ALL patients, if they have relapsed after a BCMA-directed CAR-T cellular therapy then:

• Treatment with a CAR-T must have been associated with a response of PR or better, and

• If CAR-T cellular therapy was the most recent prior therapy, excluding corticosteroids, then treatment must have been a minimum of 60 days prior to treatment with linvoseltamab.

Критерии исключения

1\. Diagnosis of plasma cell leukemia, primary systemic light-chain amyloidosis, (excluding myeloma-associated amyloidosis), Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) 2. Patients with known MM brain lesions or meningeal involvement 3. Cardiac ejection fraction <40% by echocardiogram or multi-gated acquisition scan (MUGA) 4. Prior treatment with BCMA-directed immunotherapies, including BCMA bispecific antibodies and BiTEs. Note: BCMA antibody-drug conjugates are not excluded and BCMA-directed CAR-T treatment is not excluded in Phase 2 Cohort 3.

5\. History of allogeneic stem cell transplantation at any time, or autologous stem cell transplantation within 12 weeks of the start of study treatment

Note: Other protocol defined inclusion / exclusion criteria apply

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 14 центров

• Sylvester Comprehensive Cancer Center — Miami
• Moffitt Cancer Center - McKinley Drive — Tampa
• Emory University Hospital — Atlanta
• Indiana University_Michigan Street — Indianapolis
• Norton Cancer Institute — Louisville
• C. S. Mott_University of Michigan — Ann Arbor
• Barbara Ann Karmanos Cancer Center — Detroit
• Rutgers Cancer Institute of New Jersey — New Brunswick
• … и ещё 6 центров

Япония · 10 центров

• Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital — Nagoya
• Nagoya City University Hospital — Nagoya
• National Cancer Center Hospital East — Kashiwa-shi
• Gunma University Hospital — Maebashi
• Ibaraki Prefectural Central Hospital — Kasama-shi
• University Hospital Kyoto Prefectural Univ of Medicine — Kyoto
• Saitama Medical University International Medical Center — Hidaka
• Tokushima Prefectural Central Hospital — Tokushima
• … и ещё 2 центра

Испания · 6 центров

• Hospital de la Santa Creu i Sant Pau — Barcelona
• Clinica Universidad de Navarra — Pamplona
• Universitary Hospital La Princesa — Madrid
• Hospital Universitario Ramon y Cajal — Madrid
• Hospital Universitario 12 de Octubre — Madrid
• Hospital Clinico Universitario de Salamanca — Salamanca

South Korea · 4 центра

• National Cancer Center Korea — Goyang
• Seoul National University Cancer Hospital — Seoul
• The Catholic University of Korea, Seoul St. Mary's Hospital — Seoul
• Yonsei University College of Medicine, Severance Hospital — Seoul

Германия · 3 центра

• Universitatsklinikum Essen — Essen
• Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz KoeR — Mainz
• Universitatsklinikum Wurzburg — Würzburg

Бельгия · 2 центра

• ZNA Psychiatrisch Ziekenhuis Stuivenberg — Antwerp
• Cliniques Universitaires Saint-Luc — Brussels

Великобритания · 1 центр

• Royal Marsden Hospital — Sutton

Публикации

• Lee HC, Zonder JA, Dhodapkar MV, Jagannath S, Hoffman JE, Suvannasankha A, Shah MR, Lentzsch S, Baz R, Maly JJ, Namburi S, Pianko MJ, Ye JC, Wu KL, Silbermann R, Min CK, Vekemans MC, Munder M, Byun JM, Martinez-Lopez J, DeVeaux M, Roccia T, Chokshi D, Seraphin M, Knorr K, Boyapati A, Hazra A, Rodriguez Lorenc K, Kroog GS, Bumma N, Richter J. Linvoseltamab in Patients With Relapsed/Refractory Multi PMID 41387038
• Bumma N, Richter J, Jagannath S, Lee HC, Hoffman JE, Suvannasankha A, Zonder JA, Shah MR, Lentzsch S, Baz R, Maly JJ, Namburi S, Pianko MJ, Ye JC, Wu KL, Silbermann R, Min CK, Vekemans MC, Munder M, Byun JM, Martinez-Lopez J, Cassady K, DeVeaux M, Chokshi D, Boyapati A, Hazra A, Yancopoulos GD, Sirulnik LA, Rodriguez Lorenc K, Kroog GS, Houvras Y, Dhodapkar MV. Linvoseltamab for Treatment of Relap PMID 38879802

Идентификаторы

NCT: NCT03761108 · R5458-ONC-1826 · 2024-511454-45-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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