A Study of the Combination of Talquetamab and Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma (RedirecTT-1)

A Phase 1b/2 Dose Escalation and Expansion Study of the Combination of the Bispecific T Cell Redirection Antibodies Talquetamab and Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma

The purpose of this study is to identify the recommended Phase 2 regimen(s) (RP2R[s]) and schedule for the study treatment (Part 1), to characterize the safety of the RP2R(s) for the study treatment (Part 2) and to evaluate the anticancer activity of talquetamab + teclistamab in participants with relapsed or refractory multiple myeloma and extramedullary disease (EMD) (Part 3).

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Talquetamab; Drug: Teclistamab; Drug: Daratumumab

Detailed Description

Multiple myeloma is a malignant plasma cell disorder characterized by production of monoclonal proteins (M proteins), which are comprised of pathologic immunoglobulins (Ig) or fragments of such, which have subsequently lost their normal function. Rationale for combining talquetamab and teclistamab is the targeting of multiple proteins on the surface of multiple myeloma cells resulting in cell lysis. This study consists of 3 periods: screening phase (up to 28 days), treatment phase (start of study drug administration and continues until the completion of the end of treatment [EOT] visit); and a post-treatment follow-up phase (after end of treatment and up to 16 weeks after last dose of study drug(s) for each participant). End of study is defined as 2 years after the last participant has received his or her initial dose of the treatment combination. Total duration of study is Approximately 5 years. Efficacy, safety, pharmacokinetics (PK), immunogenicity, and biomarkers will be assessed at specified time points during this study. Participants safety and study conduct will be monitored throughout the study.

• Study Type: Interventional
• Enrollment (Estimated): 208
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Study Contact; Phone Number: 844-434-4210; Email: Participate-In-This-Study@its.jnj.com

Study Locations

• Australia
  • Fitzroy, Australia, 3065
    • Recruiting
    • St. Vincent's Hospital Melbourne
  • Perth, Australia, 6000
    • Recruiting
    • Royal Perth Hospital
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Recruiting
      • Tom Baker Cancer Centre
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Recruiting
      • Alberta Health Services
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X6
      • Recruiting
      • Princess Margaret Cancer Centre University Health Network
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Recruiting
      • McGill University Health Centre
• Israel
  • Jerusalem, Israel, 91120
    • Recruiting
    • Hadassah Medical Center
  • Ramat Gan, Israel, 52621
    • Recruiting
    • Sheba Medical Center
  • Tel-Aviv, Israel, 64239
    • Recruiting
    • Tel-Aviv Sourasky Medical Center
• Japan
  • Kanazawa, Japan, 920-8641
    • Recruiting
    • Kanazawa University Hospital
  • Nagoya, Japan, 467 8602
    • Recruiting
    • Nagoya City University Hospital
  • Osaka, Japan, 565-0871
    • Recruiting
    • Osaka University Hospital
  • Sendai shi, Japan, 980 8574
    • Recruiting
    • Tohoku University Hospital
  • Shibuya, Japan, 150-8935
    • Recruiting
    • Japanese Red Cross Medical Center
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Recruiting
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Recruiting
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 06591
    • Recruiting
    • The Catholic University of Korea Seoul St. Mary'S Hospital
  • Seoul, Korea, Republic of, 03722
    • Recruiting
    • Severance Hospital Yonsei University Health System
• Spain
  • Badalona, Spain, 08916
    • Recruiting
    • Hosp. Univ. Germans Trias I Pujol
  • Barcelona, Spain, 08036
    • Recruiting
    • Hosp. Clinic de Barcelona
  • L Hospitalet De Llobregat, Spain, 08908
    • Recruiting
    • Inst. Cat. Doncologia-H Duran I Reynals
  • Madrid, Spain, 28040
    • Recruiting
    • Hosp. Univ. Fund. Jimenez Diaz
  • Madrid, Spain, 28041
    • Recruiting
    • UNIV. HOSP. October 12
  • Pamplona, Spain, 31008
    • Recruiting
    • Clinica Univ. de Navarra
  • Salamanca, Spain, 37007
    • Recruiting
    • Hosp. Clinico Univ. de Salamanca
  • Santander, Spain, 39008
    • Recruiting
    • Hosp. Univ. Marques de Valdecilla
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • University of Alabama at Birmingham, Comprehensive Cancer Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Recruiting
      • University of Arkansas for Medical Sciences
  • Colorado
    • Denver, Colorado, United States, 80218
      • Recruiting
      • Colorado Blood Cancer Institute
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63130
      • Recruiting
      • Washington University in St. Louis
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10029
      • Recruiting
      • Mount Sinai Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Atrium Health
    • Winston-Salem, North Carolina, United States, 27157
      • Recruiting
      • Wake Forest University Baptist Medical Center (WFUBMC) - Comprehensive Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Science University
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Documented initial diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria
• Part 1 and 2: Participant could not tolerate or has disease that is relapsed or refractory to established therapies, including the last line of therapy. Part 3: (a) Relapsed or refractory disease, and exposed to a PI, IMiD, and an anti-CD38 mAb; (b) Documented evidence of progressive disease based on investigator's determination of response by IMWG criteria on or after their last regimen
• Part 1 and Part 2: Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1 at screening and immediately before the start of study drug administration. Part 3: ECOG performance status grade of 0, 1, or 2 at screening and immediately before the start of study drug administration

Exclusion Criteria:

• All Parts: Targeted therapy, epigenetic therapy, or treatment with an investigational treatment or an invasive investigational medical device within 21 days or at least 5 half-lives, whichever is less. Part 3: prior BCMA targeted bispecific antibody therapy; prior GPRC5D targeted therapy
• All Parts: Allogeneic stem cell transplant within 6 months before the first dose of study treatment.
• All Parts: Central nervous system involvement or clinical signs of meningeal involvement of multiple myeloma.
• All Parts: Active plasma cell leukemia (greater than [>]2.0*10^9/L plasma cells by standard differential), Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M- protein, and skin changes), or primary amyloid light chain amyloidosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Dose Escalation; Participants will receive tec+tal with or without daratumumab in 28-day cycles following initial step-up doses.	Drug: Talquetamab; Talquetamab will be administered by subcutaneous (SC) injection.; Other Names: JNJ-64407564; Drug: Teclistamab; Teclistamab will be administered by SC injection.; Other Names: JNJ-64007957; Drug: Daratumumab; Daratumumab will be administered by SC injection.
Experimental: Part 2: Dose Expansion; Participants will receive treatment doses (combination of tal+tec and dara+tal+tec regimens) which will be determined by the recommended Phase 2 regimen (s) (RP2R[s]) of the study treatment identified in Part 1.	Drug: Talquetamab; Talquetamab will be administered by subcutaneous (SC) injection.; Other Names: JNJ-64407564; Drug: Teclistamab; Teclistamab will be administered by SC injection.; Other Names: JNJ-64007957; Drug: Daratumumab; Daratumumab will be administered by SC injection.
Experimental: Part 3: Phase 2; Participants will receive teclistamab + talquetamab combination therapy, at the RP2R selected from Part 1 and Part 2.	Drug: Talquetamab; Talquetamab will be administered by subcutaneous (SC) injection.; Other Names: JNJ-64407564; Drug: Teclistamab; Teclistamab will be administered by SC injection.; Other Names: JNJ-64007957

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Approximately 5 years
Part 1: Severity of DLT as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)	Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening, and Grade 5= Death related to adverse event.	Approximately 5 years
Part 2: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability	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, is medically important.	Approximately 5 years
Part 2: Number of Participants with Adverse Events and SAEs by Severity	Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening, and Grade 5= Death related to adverse event.	Approximately 5 years
Part 3: Overall Response Rate (ORR)	ORR is defined as the percentage of participants who have a partial response (PR) or better according Independent Review Committees (IRC).	Approximately 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parts 1, 2 and 3: Serum Concentration of Talquetamab	Serum samples will be analyzed to determine concentrations of talquetamab using a validated, specific, and sensitive immunoassay method.	Approximately 5 years
Parts 1, 2 and 3: Serum Concentration of Teclistamab	Serum samples will be analyzed to determine concentrations of teclistamab using a validated, specific, and sensitive immunoassay method.	Approximately 5 years
Part 1 and Part 2: Serum Concentration of Daratumumab	Serum samples will be analyzed to determine concentrations of daratumumab using a validated, specific, and sensitive immunoassay method.	Approximately 5 years
Parts 1, 2 and 3: Number of Participants with Anti-Drug Antibodies to Talquetamab	Number of participants with anti-drug antibodies to talquetamab will be assessed.	Approximately 5 years
Parts 1, 2 and 3: Number of Participants with Anti-Drug Antibodies to Teclistamab	Number of participants with anti-drug antibodies to teclistamab will be assessed.	Approximately 5 years
Part 1 and Part 2: Number of Participants with Anti-Drug Antibodies to Daratumumab	Number of participants with anti-drug antibodies to daratumumab will be assessed.	Approximately 5 years
Part 1 and Part 2: 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.	Approximately 5 years
Parts 1, 2 and 3: Very Good Partial Response (VGPR) or Better Response Rate	VGPR or better response rate (sCR+CR+VGPR) is defined as the percentage of participants who achieve a VGPR or better response according to the IMWG criteria.	Approximately 5 years
Parts 1, 2 and 3: Complete Response (CR) or Better Response Rate	CR or better response rate (sCR+CR) is defined as the percentage of participants who achieve a CR or better response according to the IMWG criteria.	Approximately 5 years
Parts 1, 2 and 3: Duration of Response (DOR)	DOR will be calculated among responders (with PR or better) 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.	Approximately 5 years
Parts 1, 2 and 3: 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.	Approximately 5 years
Part 3: Progression free Survival (PFS)	PFS is defined as the time from the date of first dose to the date of first documented disease progression, as defined in the IMWG criteria, or death due to any cause, whichever occurs first.	Approximately 5 years
Part 3: Overall Survival (OS)	OS is measured from the date of first dose to the date of the participant's death.	Approximately 5 years
Part 3: Number of Participants with Adverse Events	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.	Approximately 5 years
Part 3: Number of Participants with Adverse Events by Severity	Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening, and Grade 5= Death related to adverse event.	Approximately 5 years
Part 1, 2 and 3: Stringent Complete Response (sCR) Rate	sCR rate is defined as the percentage of participants who achieve a sCR according to the IMWG criteria.	Approximately 5 years

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2020
• Primary Completion (Estimated): June 27, 2025
• Study Completion (Estimated): August 29, 2025

Study Registration Dates

• First Submitted: October 12, 2020
• First Submitted That Met QC Criteria: October 12, 2020
• First Posted (Actual): October 14, 2020

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Antineoplastic Agents; Daratumumab
• Other Study ID Numbers: CR108901; 2019-004124-38 (EudraCT Number); 64007957MMY1003 (Other Identifier: Janssen Research & Development, LLC); 2023-503439-16-00 (Registry Identifier: EUCT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes