A Study of Subcutaneous Daratumumab Regimens in Combination With Bispecific T Cell Redirection Antibodies for the Treatment of Participants With Multiple Myeloma

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04108195
• Other study ID #: CR108620
• Secondary ID: 2019-000330-1964
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: February 21, 2020
• Est. completion date: August 22, 2025

Study information

• Verified date: June 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 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, with or without pomalidomide, in combination with talquetamab and teclistamab, 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) and a post treatment follow-up period (after end of treatment and up to 16 weeks after last dose. End of study is defined as last study assessment for last participant in study. Total duration of study is approximately 2.4 years. 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 290
• Est. completion date: August 22, 2025
• Est. primary completion date: September 9, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Daratumumab
Participants will receive daratumumab.
• Talquetamab
Participants will receive talquetamab.
• Teclistamab
Participants will receive teclistamab.
• Pomalidomide
Participants will receive pomalidomide.

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	University Health Network UHN Princess Margaret Cancer Centre	Toronto	Ontario
Germany	Universitatsklinikum Freiburg	Freiburg
Germany	Universitaetsklinikum Hamburg Eppendorf	Hamburg
Germany	Universitaetsklinikum Heidelberg	Heidelberg
Germany	Universitatsklinikum Wurzburg	Wuerzburg
Netherlands	VU Medisch Centrum	Amsterdam
Netherlands	LUMC	Leiden
Spain	Germans Trias I Pujol	Barcelona
Spain	Hosp Clinic de Barcelona	Barcelona
Spain	Inst. Cat. Doncologia-H Duran I Reynals	Barcelona
Spain	Hosp Univ Fund Jimenez Diaz	Madrid
Spain	Clinica Univ. de Navarra	Pamplona
Spain	Hosp Clinico Univ de Salamanca	Salamanca
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	City of Hope National Medical Center	Duarte	California
United States	Medical College Of Wisconsin	Milwaukee	Wisconsin
United States	Vanderbilt - Ingram Cancer Center	Nashville	Tennessee
United States	Mount Sinai Medical Center	New York	New York
United States	The Blavatnik Family Chelsea Medical Center at Mount Sinai	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of California San Francisco	San Francisco	California
United States	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Canada,  Germany,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Number of Participants With Dose Limiting Toxicity (DLT)	The dose limiting toxicities are based on drug related adverse events and defined as any of the following events: hematological or non-hematological toxicity of grade 3 or higher.	Up to 52 Weeks
Primary	Part 1: Number of Participants With Dose Limiting Toxicity by Severity	The dose limiting toxicities are based on drug related adverse events and defined as any of the following events: hematological or non-hematological toxicity of grade 3 or higher.	Up to 52 Weeks
Primary	Part 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect, and suspects transmission of any infectious agent via a medicinal product.	Up to 48 Weeks
Primary	Part 2: Number of Participants With Adverse Events and SAEs by Severity	An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect, and suspects transmission of any infectious agent via a medicinal product.	Up to 48 Weeks
Secondary	Serum Concentration of Daratumumab	Serum concentration of daratumumab will be assessed.	Up to 52 Weeks
Secondary	Serum Concentration of Talquetamab	Serum concentration of talquetamab will be assessed.	Up to 52 Weeks
Secondary	Serum Concentration of Teclistamab	Serum concentration of teclistamab will be assessed.	Up to 52 Weeks
Secondary	Biomarker Assessment of Daratumumab	Serum cytokine concentrations will be measured at the time of drug infusion of daratumumab for biomarker assessment.	Up to Cycle 7 Day 1 (each cycle of 28-days)
Secondary	Biomarker Assessment of Talquetamab	Serum cytokine concentrations will be measured at the time of drug infusion of talquetamab for biomarker assessment.	Up to Cycle 7 Day 1 (each cycle of 28-days)
Secondary	Biomarker Assessment of Teclistamab	Serum cytokine concentrations will be measured at the time of drug infusion of teclistamab for biomarker assessment.	Up to Cycle 7 Day 1 (each cycle of 28-days)
Secondary	Number of Participants With Anti-Drug Antibodies to Daratumumab	Number of participants with anti-drug antibodies to daratumumab will be assessed.	Up to 52 Weeks
Secondary	Number of Participants With Anti-Drug Antibodies to Talquetamab	Number of participants with anti-drug antibodies to talquetamab will be assessed.	Up to 52 Weeks
Secondary	Number of Participants With Anti-Drug Antibodies to Teclistamab	Number of Participants with anti-drug antibodies to teclistamab will be assessed.	Up to 52 Weeks
Secondary	Overall Response Rate (ORR)	ORR is defined as the percentage of participants who have a partial response (PR) or better according to the International Myeloma Working Group (IMWG) criteria.	Up to 48 Weeks
Secondary	Clinical Benefit Rate	Clinical benefit rate (ORR + minimal response [MR]) is defined as the of participants who have a MR or better according to the IMWG criteria.	Up to 48 Weeks
Secondary	Duration of Response (DOR)	DOR is defined as the time from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the IMWG criteria.	Up to 48 Weeks
Secondary	Time to Response	Time to response is defined as the time between date of first dose of study drug and the first efficacy evaluation that the participant has met all criteria for PR or better.	Up to 48 Weeks