Clinical trial NCT04108195: A Study of Subcutaneous Daratumumab Regimens in Combination With Bispecific T Cell Redirection Antibodies for the Treatment of Participants With Multiple Myeloma
Official title: A Phase 1b Study of Subcutaneous Daratumumab Regimens in Combination With Bispecific T Cell Redirection Antibodies for the Treatment of Subjects With Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Multiple Myeloma
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2019-09-30
Enrollment: 290
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 identify recommended Phase 2 doses (RP2Ds) for each treatment combination (between daratumumab plus talquetamab and teclistamab plus daratumumab with or without pomalidomide) and to characterize the safety of each RP2D for selected treatment combinations.

Detailed description: Multiple myeloma is a malignant plasma cell disorder characterized by osteolytic lesions, increased susceptibility to infections, hypercalcemia, and renal failure. Overall rationale of study is that daratumumab in combination with talquetamab or teclistamab with or without pomalidomide may lead to enhanced clinical responses in treatment of relapsed or refractory multiple myeloma through multiple mechanisms of action. Daratumumab is human immunoglobulin G1 kappa monoclonal antibody (IgG1k) that binds with high affinity to a unique epitope on cluster of differentiation 38 (CD38) in a variety of hematological malignancies including multiple myeloma. Talquetamab and teclistamab are bispecific T cell redirection antibodies. Talquetamab binds to cluster of differentiation 3 (CD3) receptor complex on T cells and to G protein-coupled receptor family C group 5-member D (GPRC5D), a 7-transmembrane receptor protein on plasma cells and teclistamab binds to human and cynomolgus-CD3 and B cell maturation antigen (BCMA). Purpose of study is to evaluate safety of daratumumab in combination with talquetamab and teclistamab with or without pomalidomide, and to evaluate preliminary antitumor activity of each combination. Study consists of a screening period, treatment period (Part 1: dose escalation and Part 2: dose expansion), a Post-treatment Follow-up Period (after the last dose of study drug and will continue for up to 16 weeks for each subject), and a Long-term Extension Period. The study will end when one of the following occurs: 1) the study drug has received marketing authorization and, if regionally applicable, government reimbursement is available; 2) a long-term extension rollover study has commenced for participants who are still benefiting from study treatment as determined by their investigator; or 3) all participants have discontinued study treatment. Total duration of study is approximately 5 years and 6 months. Efficacy, safety, pharmacokinetics (PK), immunogenicity, and biomarkers will be assessed at specified time points. Participants safety will be monitored throughout study by Study Evaluation Team (SET). SET consists of members of sponsor's study team and participating investigators.

Eligibility criteria: Inclusion Criteria:

* Documented initial diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria
* Must have either of the following: a) received at least 3 prior lines of therapy including a proteasome inhibitor (PI) (greater than or equal to \[\>=\] 2 cycles or 2 months of treatment) and an immunomodulatory drug (IMiD) (\>=2 cycles or 2 months of treatment) in any order during the treatment or b) disease that is double refractory to a PI and an IMiD
* Measurable disease at screening as defined by any of the following: Serum monoclonal protein (M-protein) level \>=1.0 grams per deciliter (g/dL) (in non- immunoglobulin G (IgG) myeloma, an M-protein level \>=0.5 g/dL); or Urine M-protein level \>=200 milligrams (mg)/24 hours; or Light chain multiple myeloma: Serum immunoglobulin (Ig) free light chain (FLC) \>=10 milligrams per deciliter (mg/dL) and abnormal serum Ig kappa lambda FLC ratio
* Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1 at screening and at Cycle 1, Day 1 predose
* Female participants of childbearing potential must have a negative highly-sensitive serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test (less than \[\<\] 5 international units per milliliter \[IU/mL\]) at screening and a negative urine or serum pregnancy test within 1 day before the first dose of study drug

Exclusion Criteria:

* Treatment in the prior 3 months with an anti- cluster of differentiation 38 (CD38) therapy (example, daratumumab), or discontinuation of a prior anti-CD38 therapy at any time due to an adverse event related to the anti-CD38 therapy
* Live, attenuated vaccine within 4 weeks prior to the first dose of study drug unless approved by sponsor
* Active Central nervous system involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. If either is suspected, brain magnetic resonance imaging (MRI) and lumbar cytology are required
* Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). Participants with resolved infection must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded
* Active hepatitis C infection as measured by positive hepatitis C virus- ribonucleotide (HCV)-RNA testing. Participants with a history of Hepatitis C virus antibody positivity must undergo HCV-RNA testing

Primary outcomes:
measure: Part 1: Number of Participants With Dose Limiting Toxicity (DLT)
timeFrame: Up to 52 Weeks
measure: Part 1: Number of Participants With Dose Limiting Toxicity by Severity
timeFrame: Up to 52 Weeks
measure: Part 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to 48 Weeks
measure: Part 2: Number of Participants With Adverse Events and SAEs by Severity
timeFrame: Up to 48 Weeks
Secondary outcomes:
measure: Serum Concentration of Daratumumab
timeFrame: Up to 52 Weeks
measure: Serum Concentration of Talquetamab
timeFrame: Up to 52 Weeks
measure: Serum Concentration of Teclistamab
timeFrame: Up to 52 Weeks
measure: Biomarker Assessment of Daratumumab
timeFrame: Up to Cycle 7 Day 1 (each cycle of 28-days)
measure: Biomarker Assessment of Talquetamab
timeFrame: Up to Cycle 7 Day 1 (each cycle of 28-days)
measure: Biomarker Assessment of Teclistamab
timeFrame: Up to Cycle 7 Day 1 (each cycle of 28-days)
measure: Number of Participants With Anti-Drug Antibodies to Daratumumab
timeFrame: Up to 52 Weeks
measure: Number of Participants With Anti-Drug Antibodies to Talquetamab
timeFrame: Up to 52 Weeks
measure: Number of Participants With Anti-Drug Antibodies to Teclistamab
timeFrame: Up to 52 Weeks
measure: Overall Response Rate (ORR)
timeFrame: Up to 48 Weeks
measure: Clinical Benefit Rate
timeFrame: Up to 48 Weeks
measure: Duration of Response (DOR)
timeFrame: Up to 48 Weeks
measure: Time to Response
timeFrame: Up to 48 Weeks
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Irvine
country: United States
facility: City of Hope Orange County Lennar Foundation Cancer Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: New York
country: United States
facility: The Blavatnik Family Chelsea Medical Center at Mount Sinai
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Ingram Cancer Center
state: Tennessee
city: Milwaukee
country: United States
facility: Medical College Of Wisconsin
state: Wisconsin
city: Calgary
country: Canada
facility: Arthur J E Child Comprehensive Cancer Centre
state: Alberta
city: Toronto
country: Canada
facility: University Health Network UHN Princess Margaret Cancer Centre
state: Ontario
city: Freiburg
country: Germany
facility: Universitatsklinikum Freiburg
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg Eppendorf
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg
city: Wuerzburg
country: Germany
facility: Universitatsklinikum Wurzburg
city: Amsterdam
country: Netherlands
facility: VU Medisch Centrum
city: Leiden
country: Netherlands
facility: LUMC
city: Barcelona
country: Spain
facility: Hosp Clinic de Barcelona
city: Barcelona
country: Spain
facility: Inst. Cat. Doncologia-H Duran I Reynals
city: Barcelona
country: Spain
facility: Germans Trias I Pujol
city: Madrid
country: Spain
facility: Hosp Univ Fund Jimenez Diaz
city: Pamplona
country: Spain
facility: Clinica Univ. de Navarra
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, Powers G, Luistro L, Babich A, Baldwin E, Li Y, Zhang X, Mendonca M, Majewski N, Nanjunda R, Chin D, Packman K, Elsayed Y, Attar R, Gaudet F. Teclistamab is an active T cell-redirecting bispecific antibody against B-cell maturation antigen for multiple myeloma. Blood Adv. 2020 Sep 22;4(18):4538-4549. doi: 10.1182/bloodadvances.2020002393.