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

NCT04108195 | Active Not Recruiting Phase 1 FDA Drug

• 4 other identifiers: CR10862064407564MMY10022019-000330-192023-503468-17-00
• Study Type: interventional
• Target: 290
• Locations: 5 countries
• Sites: 24

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.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• 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

• 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 Outcomes (13)

• Serum Concentration of Daratumumab

  Up to 52 Weeks

• Serum Concentration of Talquetamab

  Up to 52 Weeks

• Serum Concentration of Teclistamab

  Up to 52 Weeks

• Biomarker Assessment of Daratumumab

  Up to Cycle 7 Day 1 (each cycle of 28-days)

• Biomarker Assessment of Talquetamab

  Up to Cycle 7 Day 1 (each cycle of 28-days)

Study Arms (2)

Part 1: Dose Escalation

EXPERIMENTAL

Participants will be assigned to either a combination of 1) daratumumab plus teclistamab or 2) daratumumab plus talquetamab or 3) daratumumab plus talquetamab plus pomalidomide or 4) daratumumab plus teclistamab plus pomalidomide.

Drug: Daratumumab; Drug: Talquetamab; Drug: Teclistamab; Drug: Pomalidomide

Part 2: Dose Expansion

EXPERIMENTAL

Participants will be treated with the RP2D(s) for selected treatment combinations determined in Part 1.

Drug: Daratumumab; Drug: Talquetamab; Drug: Teclistamab; Drug: Pomalidomide

Interventions

Daratumumab DRUG

Participants will receive daratumumab.

Also known as: JNJ-54767414, Darzalex

Part 1: Dose Escalation; Part 2: Dose Expansion

Talquetamab DRUG

Participants will receive talquetamab.

Also known as: JNJ-64407564

Part 1: Dose Escalation; Part 2: Dose Expansion

Teclistamab DRUG

Participants will receive teclistamab.

Also known as: JNJ-64007957

Part 1: Dose Escalation; Part 2: Dose Expansion

Pomalidomide DRUG

Participants will receive pomalidomide.

Part 1: Dose Escalation; Part 2: Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (24)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

City of Hope Orange County Lennar Foundation Cancer Center

Irvine, California, 92618, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

The Blavatnik Family Chelsea Medical Center at Mount Sinai

New York, New York, 10011, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Medical College Of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Arthur J E Child Comprehensive Cancer Centre

Calgary, Alberta, T2N 5G2, Canada

Location

University Health Network UHN Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Universitatsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Universitaetsklinikum Hamburg Eppendorf

Hamburg, 20246, Germany

Location

Universitaetsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Universitatsklinikum Wurzburg

Würzburg, 97080, Germany

Location

VU Medisch Centrum

Amsterdam, 1081 HV, Netherlands

Location

LUMC

Leiden, 2333ZA, Netherlands

Location

Hosp Clinic de Barcelona

Barcelona, 08036, Spain

Location

Inst. Cat. Doncologia-H Duran I Reynals

Barcelona, 08908, Spain

Location

Germans Trias I Pujol

Barcelona, 08916, Spain

Location

Hosp Univ Fund Jimenez Diaz

Madrid, 28040, Spain

Location

Clinica Univ. de Navarra

Pamplona, 31008, Spain

Location

Hosp Clinico Univ de Salamanca

Salamanca, 37007, Spain

Location

Related Publications (2)

• Chari A, van de Donk NWCJ, Dholaria B, Weisel K, Mateos MV, Goldschmidt H, Martin TG, Morillo D, Reece D, Rodriguez-Otero P, Bhutani M, D'Souza A, Oriol A, Rosinol L, Bahlis NJ, Vishwamitra D, Skerget S, Verona RI, Bakshi K, Kang L, Prior TJ, Vandenberk L, Tolbert J, Lee S, Smit MD, Wasch R. Talquetamab plus daratumumab for the treatment of relapsed or refractory multiple myeloma in the TRIMM-2 study. Blood. 2025 Dec 11;146(24):2902-2913. doi: 10.1182/blood.2025029360.

  PMID: 40983036 DERIVED

• 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.

  PMID: 32956453 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumab; talquetamab; pomalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2019
• First Posted: September 30, 2019
• Study Start: February 21, 2020
• Primary Completion (Estimated): April 7, 2027
• Study Completion (Estimated): April 7, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (10); CA (2); DE (4); NL (2); ES (6)