Clinical trial NCT03761108: Phase 1/2 Study of REGN5458 in Adult Patients With Relapsed or Refractory Multiple Myeloma
Official title: Phase 1/2 FIH Study of REGN5458 (Anti-BCMA x Anti-CD3 Bispecific Antibody) in Patients With Relapsed or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Keywords: Relapsed, Refractory
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2018-12-03
Enrollment: 387
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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


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

Primary outcomes:
measure: Incidence of dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period
timeFrame: Up to 28 days
measure: Incidence and severity of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 5 years
measure: Incidence and severity of adverse events of special interest (AESI)
timeFrame: Up to 5 years
measure: Concentrations of REGN5458 in serum over time
timeFrame: Up to 5 years
measure: Objective response rate (ORR) as determined by an Independent Review Committee (IRC)
timeFrame: Up to 5 years
measure: Incidence and severity of cytokine release syndrome (CRS) with REGN5458
timeFrame: Up to 5 years
measure: ORR of IV REGN5458 as assessed by investigator in patients who have progressed
timeFrame: Up to 5 years
Secondary outcomes:
measure: Concentrations of REGN5458 in the serum over time
timeFrame: Up to 5 years
measure: Incidence over time of anti-drug antibodies (ADAs) to REGN5458
timeFrame: Up to 5 years
measure: Titer of anti-drug antibodies (ADAs) to REGN5458 over time
timeFrame: Up to 5 years
measure: Incidence of neutralizing antibodies (Nab) to REGN5458 over time
timeFrame: Up to 5 years
measure: Duration of response (DOR) as determined by an IRC, measured using the IMWG criteria
timeFrame: Up to 5 years
measure: DOR as determined by an investigator, measured using the International Myeloma Working Group (IMWG) criteria
timeFrame: Up to 5 years
measure: Progression-free survival (PFS) as determined by an IRC, measured using the IMWG criteria
timeFrame: Up to 5 years
measure: PFS as determined by an investigator, measured using the IMWG criteria
timeFrame: Up to 5 years
measure: Rate of minimal residual disease (MRD) negative status using the IMWG criteria
timeFrame: Up to 5 years
measure: Rate of MRD negative status status
timeFrame: Up to 5 years
measure: Overall survival (OS)
timeFrame: Up to 5 years
measure: ORR as measured as determined by blinded IRC, as measured using the IMWG criteria
timeFrame: Up to 5 years
measure: ORR as determined by the investigator, measured using the IMWG criteria
timeFrame: Up to 5 years
measure: 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)
timeFrame: Up to 5 years
measure: Effects of REGN5458 on HRQOL and patient-reported symptoms and functioning per Quality of Life Questionnaire-Multiple Myeloma module 20 [QLQ-MY20])
timeFrame: Up to 5 years
measure: Effects of REGN5458 on HRQOL and patient-reported symptoms and functioning per EuroQoL-5 Dimension-3 Level Scale [EQ-5D-3L])
timeFrame: Up to 5 years
measure: Change in patient-reported global health status/QoL per EORTC QLQ-C30
timeFrame: Baseline up to Up to 5 years
measure: Time to definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30
timeFrame: Up to 5 years
measure: Effects of REGN5458 on general health status per EQ-5D-3L
timeFrame: Up to 5 years
measure: Effects of REGN5458 on patient-reported functions and symptoms per EORTC QLQ-C30
timeFrame: Up to 5 years
measure: Effects of REGN5458 on patient-reported functions and symptoms per QLQ-MY20
timeFrame: Up to 5 years
measure: Incidence and severity of TEAEs with REGN5458
timeFrame: Up to 5 years
measure: Incidence and severity of AESIs with REGN5458
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center - McKinley Drive
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University_Michigan Street
state: Indiana
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Ann Arbor
country: United States
facility: C. S. Mott_University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Center
state: Michigan
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Columbus
country: United States
facility: Ohio State University James Cancer Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University (OHSU) Marquam Hill Campus
state: Oregon
city: Houston
country: United States
facility: University of Texas MD Anderson Clinic
state: Texas
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Antwerp
country: Belgium
facility: ZNA Psychiatrisch Ziekenhuis Stuivenberg
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Essen
country: Germany
facility: Universitatsklinikum Essen
state: North Rhine-Westphalia
city: Mainz
country: Germany
facility: Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz KoeR
state: Rheinland-Pfalz
city: Würzburg
country: Germany
facility: Universitatsklinikum Wurzburg
city: Nagoya
country: Japan
facility: Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital
state: Aichi
city: Nagoya
country: Japan
facility: Nagoya City University Hospital
state: Aichi
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East
state: Chiba-ken
city: Maebashi
country: Japan
facility: Gunma University Hospital
state: Gunma
city: Kasama-shi
country: Japan
facility: Ibaraki Prefectural Central Hospital
state: Ibaraki
city: Kyoto City
country: Japan
facility: University Hospital Kyoto Prefectural Univ of Medicine
state: Kyoto
city: Hidaka
country: Japan
facility: Saitama Medical University International Medical Center
state: Saitama
city: Tokushima-shi
country: Japan
facility: Tokushima Prefectural Central Hospital
state: Tokushima
city: Shibuya-ku
country: Japan
facility: Japanese Red Cross Medical Center. 4-1-22 Hiroo
state: Tokyo
city: Shibuya-ku
country: Japan
facility: Japanese Red Cross Medical Center
state: Tokyo
city: Tokyo
country: Japan
facility: Keio University Hospital
city: Goyang
country: Korea, Republic of
facility: Center for Hematologic Malignancy
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Cancer Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei University College of Medicine, Severance Hospital
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
state: Catalonia
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Madrid
country: Spain
facility: Universitary Hospital La Princesa
state: Salamanca
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
state: Surrey
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: