Phase 1/2 Study of REGN5458 in Adult Patients With Relapsed or Refractory Multiple Myeloma

Multiple Myeloma Clinical Trial

— LINKER-MM1  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03761108
• Other study ID #: R5458-ONC-1826
• Secondary ID: 2018-003188-78
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 23, 2019
• Est. completion date: June 24, 2032

Study information

• Verified date: December 2023
• Source: Regeneron Pharmaceuticals
• Contact: Clinical Trial Administrator
• Phone: 844-734-6643
• Email: clinicaltrials[@]regeneron.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to learn about the safety of REGN5458 and to find out what is the best dose of REGN5458 to give to patients with multiple myeloma. An additional purpose is to look for any signs that REGN5458 can treat cancer.

The study is looking at several other research questions, including:

• Side effects that may be experienced by people receiving REGN5458

• How REGN5458 works in the body

• How much REGN5458 is present in the blood

• How REGN5458 may work to treat cancer

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 387
• Est. completion date: June 24, 2032
• Est. primary completion date: May 4, 2032
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 REGN5458.

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 -Cardiac ejection fraction <40% by echocardiogram or multi-gated acquisition scan (MUGA) 3. Prior treatment with BCMA-directed immunotherapies, including BCMA bispecific antibodies and BiTEs. Note: BCMA antibody-drug conjugates are not excludedand BCMA-directed CAR-T treatment is not excluded in Phase 2 Cohort 3.

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

Note 1: Other protocol defined inclusion / exclusion criteria apply Note 2: US enrollment completed

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Linvoseltamab
Administered by IV infusion and/or SC

Locations

Country	Name	City	State
Belgium	Ziekenhuis Netwerk Antwerpen (ZNA)- Stuivenberg	Antwerp
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Germany	Universitaetsklinikum Essen	Essen
Germany	University Medicine Mainz	Mainz
Germany	Universitatsklinikum Wurzburg	Würzburg
Japan	Saitama Medical University International Medical Center. 1397-1 Oaza Yamane, Hidaka	Hidaka	Saitama
Japan	Ibaraki Prefectural Central Hospital. 6528 Koibuchi, Kasama	Kasama
Japan	University Hospital Kyoto Prefectural University of Medicine. 465 Kajii-cho, Kawaramachi-Hirokoji,Kamigyo-ku	Kyoto
Japan	Gunma University Hospital. 3-39-15 Showa-machi	Maebashi	Gunma
Japan	Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital	Nagoya	Aichi
Japan	Nagoya City University Hospital	Nagoya	Aichi
Japan	Japanese Red Cross Medical Center. 4-1-22 Hiroo	Shibuya-ku	Tokyo
Japan	Tokushima Prefectural Central Hospital. 1-10-3 Kuramoto-cho	Tokushima
Korea, Republic of	National Cancer Center	Goyang-si	Gyeonggi-do
Korea, Republic of	Seoul St.Mary's Hospital, The Catholic University of Korea Seocho-gu	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System Seodaemun-gu	Seoul
Korea, Republic of	Soul National University Hospital Jongno-gu	Seoul
Spain	Hospital Universitario Sant Pau, Carrer de Sant Antoni Maria Claret, 167	Barcelona
Spain	Hospital 12 de Octubre Avda de Cordoba, s/n	Madrid
Spain	Hospital Universitario Ramon y Cajal M-607, km 9.100	Madrid
Spain	Universitary Hospital La Princesa Calle de Diego de Leon 62	Madrid
Spain	Clinica universidad de Navarra unidad centrak de ensayos clinicos 7a 2a fase	Pamplona	Navarre
Spain	Hospital Universitario de Salamanca Paseo de San Vicente 58-182	Salamanca
United Kingdom	The Royal Marsden Hospital Downs Road Surrey	London
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	The Ohio State University, James Cancer Hospital	Columbus	Ohio
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	University of Texas MD Anderson Clinic	Houston	Texas
United States	Indiana University Melvin and Bren Simon Comprehensive Cancer Center	Indianapolis	Indiana
United States	Norton Cancer Institute	Louisville	Kentucky
United States	University of Miami Hospital/Sylvester Comprehensive	Miami	Florida
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Columbia University Medical Center, Herbert Irving Pavilion	New York	New York
United States	The Icahn School of Medicine at Mount Sinai	New York	New York
United States	Oregon Health Science University OHSU	Portland	Oregon
United States	Swedish Cancer Institute	Seattle	Washington
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Germany,  Japan,  Korea, Republic of,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period	Phase 1 and Phase 2 for Japanese cohort only	Up to 28 days
Primary	Incidence and severity of treatment-emergent adverse events (TEAEs)	Phase 1 Note: Phase 1, part 2 is not applicable for US.	Up to 5 years
Primary	Incidence and severity of adverse events of special interest (AESI)	Phase 1 Note: Phase 1, part 2 is not applicable for US.	Up to 5 years
Primary	Concentrations of REGN5458 in serum over time	Phase 1, part 2 and Phase 2, for Japanese cohort only	Up to 5 years
Primary	Objective response rate (ORR) as determined by an Independent Review Committee (IRC)	Phase 2, cohorts 1 and 2	Up to 5 years
Primary	Incidence and severity of cytokine release syndrome (CRS) with REGN5458	Phase 2, cohort 3 Note: Phase 2, Cohort 3 is not applicable for US.	Up to 5 years
Primary	ORR of IV REGN5458 as assessed by investigator in patients who have progressed	Phase 2, cohort 3 Note: Phase 2, Cohort 3 is not applicable for US.	Up to 5 years
Secondary	Concentrations of REGN5458 in the serum over time	Phase 1 part 1 and Phase 2 Note: Phase 2, Cohort 3 is not applicable for US.	Up to 5 years
Secondary	Incidence over time of anti-drug antibodies (ADAs) to REGN5458	Phase 1 and Phase 2 Note: Phase 1, part 2 and Phase 2, Cohort 3 is not applicable for US.	Up to 5 years
Secondary	Titer of anti-drug antibodies (ADAs) to REGN5458 over time	Phase 1 and Phase 2 Note: Phase 1, part 2 and Phase 2, Cohort 3 is not applicable for US.	Up to 5 years
Secondary	Incidence of neutralizing antibodies (Nab) to REGN5458 over time	Phase 1 and Phase 2 Note: Phase 1, part 2 and Phase 2, Cohort 3 is not applicable for US.	Up to 5 years
Secondary	Duration of response (DOR) as determined by an IRC, measured using the IMWG criteria	Phase 2, cohorts 1 and 2	Up to 5 years
Secondary	DOR as determined by an investigator, measured using the International Myeloma Working Group (IMWG) criteria	Phase 1 and Phase 2, cohorts 1 and 2 Note: Phase 1, part 2 is not applicable for US.	Up to 5 years
Secondary	Progression-free survival (PFS) as determined by an IRC, measured using the IMWG criteria	Phase 2, cohorts 1 and 2	Up to 5 years
Secondary	PFS as determined by an investigator, measured using the IMWG criteria	Phase 1 and Phase 2, cohorts 1 and 2 Note: Phase 1, part 2 is not applicable for US.	Up to 5 years
Secondary	Rate of minimal residual disease (MRD) negative status using the IMWG criteria	Phase 1 Note: Phase 1, part 2 is not applicable for US.	Up to 5 years
Secondary	Rate of MRD negative status status	Phase 2 Note: Phase 2, Cohort 3 is not applicable for US.	Up to 5 years
Secondary	Overall survival (OS)	Phase 1 and Phase 2 Note: Phase 1, part 2 and Phase 2, Cohort 3 is not applicable for US.	Up to 5 years
Secondary	ORR as measured as determined by blinded IRC, as measured using the IMWG criteria	Phase 1, part 1 dose level 7 (DL7)	Up to 5 years
Secondary	ORR as determined by the investigator, measured using the IMWG criteria	Phase 1 and Phase 2, cohorts 1 and 2 Note: Phase 1, part 2 is not applicable for US.	Up to 5 years
Secondary	Effects of REGN5458 on health-related quality of life (HRQoL) and patient-reported symptoms and functioning per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)	Phase 2; The EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much."; Note: Phase 2, Cohort 3 is not applicable for US.	Up to 5 years
Secondary	Effects of REGN5458 on HRQOL and patient-reported symptoms and functioning per Quality of Life Questionnaire-Multiple Myeloma module 20 [QLQ-MY20])	Phase 2; The EORTC QLQ-MY20 is a self -administered instrument to assess QoL in persons with MM. This 20-item questionnaire measures the following domains: symptom scales, including disease symptoms (6 items) and symptoms related to side effects of treatment (10 items); function scale and future perspective (3 items); and body image (1 item). A high score represents a high level of symptoms or problems.; Note: Phase 2, Cohort 3 is not applicable for US.	Up to 5 years
Secondary	Effects of REGN5458 on HRQOL and patient-reported symptoms and functioning per EuroQoL-5 Dimension-3 Level Scale [EQ-5D-3L])	Phase 2; The EQ-5D-3L is a self-administered generic standardized health status measure, consisting of an EQ-5D descriptive system and an EQ visual analog scale. The EQ-5D-3L descriptive system assesses 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is rated on a 3-level scale: no problems, some problems, and extreme problems. The EQ visual analog scale component is a vertical visual analog scale used by patients to rate their health.; Note: Phase 2, Cohort 3 is not applicable for US.	Up to 5 years
Secondary	Change in patient-reported global health status/QoL per EORTC QLQ-C30	Phase 2 Note: Phase 2, Cohort 3 is not applicable for US.	Baseline up to Up to 5 years
Secondary	Time to definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30	Phase 2 Note: Phase 2, Cohort 3 is not applicable for US.	Up to 5 years
Secondary	Effects of REGN5458 on general health status per EQ-5D-3L	Phase 2 Note: Phase 2, Cohort 3 is not applicable for US.	Up to 5 years
Secondary	Effects of REGN5458 on patient-reported functions and symptoms per EORTC QLQ-C30	Phase 2 Note: Phase 2, Cohort 3 is not applicable for US.	Up to 5 years
Secondary	Effects of REGN5458 on patient-reported functions and symptoms per QLQ-MY20	Phase 2 Note: Phase 2, Cohort 3 is not applicable for US.	Up to 5 years
Secondary	Incidence and severity of TEAEs with REGN5458	Phase 2 Note: Phase 2, Cohort 3 is not applicable for US.	Up to 5 years
Secondary	Incidence and severity of AESIs with REGN5458	Phase 2 Note: Phase 2, Cohort 3 is not applicable for US.	Up to 5 years