Clinical trial NCT03399799: Dose Escalation Study of Talquetamab in Participants With Relapsed or Refractory Multiple Myeloma
Official title: A Phase 1, First-in-Human, Open-Label, Dose Escalation Study of Talquetamab, a Humanized GPRC5D x CD3 Bispecific Antibody, in Subjects With Relapsed or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Hematological Malignancies
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2018-01-16
Enrollment: 279
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 purpose of this study is to characterize the safety of Talquetamab and to determine the recommended Phase 2 dose(s) (RP2Ds) and dosing schedule assessed to be safe for Talquetamab (Part 1 \[Dose Escalation\]) and to further characterize the safety of Talquetamab at the recommended Phase 2 dose(s) (RP2Ds) (Part 2 \[Dose Expansion\]).


Eligibility criteria: Inclusion Criteria:

* Documented initial diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria
* Part 1: Participants with measurable multiple myeloma who have progressed on, or could not tolerate, all available established therapies. Part 2: Participants with multiple myeloma measurable by central laboratory assessment who have progressed on, or could not tolerate, all available established therapies; Serum monoclonal paraprotein (M-protein) level greater than or equal to (\>=) 1.0 gram per deciliter (g/dL) or urine M-protein level \>=200 milligram per 24 hours (mg/24 h) or light chain multiple myeloma without measurable disease in the serum or the urine: serum immunoglobulin free light chain (FLC) \>= 10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio; If central laboratory assessments are not available, relevant local laboratory measurements must exceed the minimum required level by at least 25%
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
* Women of childbearing potential must have a negative pregnancy test at screening and prior to the first dose of study drug using a highly sensitive pregnancy test either serum (Beta human chorionic gonadotropin \[beta-hCG\]) or urine
* Sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study, and is willing to and able participate in the study. Consent is to be obtained prior to the initiation of any study-related tests or procedures that are not part of standard-of-care for the participant's disease

Exclusion Criteria:

* Participants who received or plan to receive any live, attenuated vaccine within 4 weeks prior to the first dose, during treatment, or within 4 weeks of the last dose of Talquetamab. Non-live or non-replicating vaccines approved or authorized for emergency use (example, coronavirus disease \[COVID\]-19) by local health authorities are allowed
* Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy
* Received a cumulative dose of corticosteroids equivalent to greater than or equal to ( \>=) 140 milligram (mg) of prednisone within the 14-day period before the first dose of study drug (does not include pretreatment medication)
* An allogenic stem cell transplant within 6 months before first dose of study drug. Participants who received an allogeneic transplant must be off all immunosuppressive medications for 6 weeks without signs of graft-versus-host disease (GVHD); and/or an autologous stem cell transplant less than or equal to (\<=) 12 weeks before first dose of study drug
* Documented history of central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. If either is suspected, whole body magnetic resonance imaging (MRI) and lumbar cytology are required

Primary outcomes:
measure: Part 1: Dose-limiting Toxicity (DLT)
timeFrame: Up to Day 28
measure: Part 1 and Part 2: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
timeFrame: From signing of Informed Consent Form (ICF) up to follow up (until 100 days after the last dose of study drug or until the start of subsequent anticancer therapy, if earlier [approximately 2.10 years])
Secondary outcomes:
measure: Part 1: Talquetamab Serum Concentrations
timeFrame: Up to 4 weeks
measure: Part 1 and Part 2: Biomarker Assessment
timeFrame: Up to Cycle 7 Day 1 (each cycle of 21-days)
measure: Part 1: Number of Participants with Talquetamab Antibodies
timeFrame: Up to 4 weeks
measure: Part 2: Overall Response Rate (ORR)
timeFrame: Approximately 2.10 years
measure: Part 2: Clinical Benefit Rate (CBR)
timeFrame: Approximately 2.10 years
measure: Part 2: Duration of Response (DOR)
timeFrame: From the date of initial documentation of a response to the date of first documented evidence of progressive disease (PD) (approximately 2.10 years)
measure: Part 2: Time to Response (TTR)
timeFrame: From the date of first dose of study drug to the date of initial documentation of a response (approximately 2.10 years)
measure: Part 2: Progression-Free Survival (PFS)
timeFrame: Every 16 weeks until end of study, participant dies, withdrawn consent, or lost to follow up (up to 18 months)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Birmingham
state: Alabama
city: Duarte
country: United States
facility: City of Hope
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Liege
country: Belgium
facility: Centre Hospitalier Universitaire de Liege Domaine Universitaire du Sart Tilman
city: Amsterdam
country: Netherlands
facility: VU Medisch Centrum
city: Utrecht
country: Netherlands
facility: UMCU
city: Badalona
country: Spain
facility: Hosp. Univ. Germans Trias I Pujol
city: Madrid
country: Spain
facility: Hosp Univ Fund Jimenez Diaz
city: Pamplona
country: Spain
facility: Clinica Univ. de Navarra
city: Pozuelo de Alarcon
country: Spain
facility: Hosp. Quiron Madrid Pozuelo
city: Salamanca
country: Spain
facility: Hosp Clinico Univ de Salamanca
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Pillarisetti K, Edavettal S, Mendonca M, Li Y, Tornetta M, Babich A, Majewski N, Husovsky M, Reeves D, Walsh E, Chin D, Luistro L, Joseph J, Chu G, Packman K, Shetty S, Elsayed Y, Attar R, Gaudet F. A T-cell-redirecting bispecific G-protein-coupled receptor class 5 member D x CD3 antibody to treat multiple myeloma. Blood. 2020 Apr 9;135(15):1232-1243. doi: 10.1182/blood.2019003342.