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NCT03761108PHASE1, PHASE2Recruiting

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

Regeneron Pharmaceuticals

Start Date

1/23/2019

Completion Date

6/16/2033

Summary

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

Eligibility Criteria

Age Range: 18 years to No maximum

Key Inclusion Criteria: 1. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 2. Confirmed diagnosis of active Multiple Myeloma (MM) by International Myeloma Working Group (IMWG) diagnostic criteria 3. 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: 1. Progression on or after at least 3 prior lines of therapy including a(n) PI, IMiD, and anti-CD38 antibody, OR 2. 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. Key Exclusion Criteria: 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

Interventions

DRUG

Linvoseltamab

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Conditions

Multiple Myeloma

Locations

Sylvester Comprehensive Cancer Center

Miami, Florida 33136

United States

Moffitt Cancer Center - McKinley Drive

Tampa, Florida 33612

United States

Emory University Hospital

Atlanta, Georgia 30322

United States

Indiana University_Michigan Street

Indianapolis, Indiana 46202

United States

Norton Cancer Institute

Louisville, Kentucky 40207

United States

C. S. Mott_University of Michigan

Ann Arbor, Michigan 48109

United States

Barbara Ann Karmanos Cancer Center

Detroit, Michigan 48201

United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey 08901

United States

Icahn School of Medicine at Mount Sinai

New York, New York 10029

United States

Columbia University Medical Center

New York, New York 10032

United States

Ohio State University James Cancer Hospital

Columbus, Ohio 43210

United States

Oregon Health and Science University (OHSU) Marquam Hill Campus

Portland, Oregon 97239

United States

University of Texas MD Anderson Clinic

Houston, Texas 77030

United States

Swedish Cancer Institute

Seattle, Washington 98104

United States

ZNA Psychiatrisch Ziekenhuis Stuivenberg

Antwerp, 2060

Belgium

Cliniques Universitaires Saint-Luc

Brussels, 1200

Belgium

Universitatsklinikum Essen

Essen, North Rhine-Westphalia 45147

Germany

Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz KoeR

Mainz, Rhineland-Palatinate 55131

Germany

Universitatsklinikum Wurzburg

Würzburg, 6 97080

Germany

Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital

Nagoya, Aichi-ken 466-8650

Japan

Nagoya City University Hospital

Nagoya, Aichi-ken 467-8602

Japan

National Cancer Center Hospital East

Kashiwa-shi, Chiba 277-8577

Japan

Gunma University Hospital

Maebashi, Gunma 371-8511

Japan

Ibaraki Prefectural Central Hospital

Kasama-shi, Ibaraki 309-1793

Japan

University Hospital Kyoto Prefectural Univ of Medicine

Kyoto, Kyoto 602-8566

Japan

Saitama Medical University International Medical Center

Hidaka, Saitama 350-1298

Japan

Tokushima Prefectural Central Hospital

Tokushima, Tokushima 770-8539

Japan

Japanese Red Cross Medical Center

Shibuya-ku, Tokyo 150-8935

Japan

Keio University Hospital

Tokyo, 160-8582

Japan

National Cancer Center Korea

Goyang, 10408

South Korea

Seoul National University Cancer Hospital

Seoul, 03080

South Korea

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, 06591

South Korea

Yonsei University College of Medicine, Severance Hospital

Seoul, 3722

South Korea

Hospital de la Santa Creu i Sant Pau

Barcelona, Catalonia 08041

Spain

Clinica Universidad de Navarra

Pamplona, Navarre 31008

Spain

Universitary Hospital La Princesa

Madrid, Salamanca 28006

Spain

Hospital Universitario Ramon y Cajal

Madrid, 28034

Spain

Hospital Universitario 12 de Octubre

Madrid, 28041

Spain

Hospital Clinico Universitario de Salamanca

Salamanca, 37007

Spain

Royal Marsden Hospital

Sutton, Surrey SM2 5PT

United Kingdom