A Study of the Combination of Talquetamab and Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma

NCT04586426 | Active Not Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: CR10890164007957MMY10032019-004124-382023-503439-16-00
• Study Type: interventional
• Target: 228
• Locations: 7 countries
• Sites: 40

Brief Summary

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).

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (5)

• 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 10 months

• 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 10 months

• 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 10 months

• 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 10 months

• 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 10 months

Secondary Outcomes (16)

• Parts 1, 2 and 3: Serum Concentration of Talquetamab

  Approximately 5 years 10 months

• Parts 1, 2 and 3: Serum Concentration of Teclistamab

  Approximately 5 years 10 months

• Part 1 and Part 2: Serum Concentration of Daratumumab

  Approximately 5 years 10 months

• Parts 1, 2 and 3: Number of Participants with Anti-Drug Antibodies to Talquetamab

  Approximately 5 years 10 months

• Parts 1, 2 and 3: Number of Participants with Anti-Drug Antibodies to Teclistamab

  Approximately 5 years 10 months

Study Arms (3)

Part 1: Dose Escalation

EXPERIMENTAL

Participants will receive tec+tal in 28-day cycles following initial step-up doses. Upon sponsor notification, participants will enter the long-term extension (LTE) Phase or Drug-access Long-term Extension (DA-LTE) Phase and will continue to receive study treatment until disease progression, unacceptable toxicity, withdrawal of consent, discontinuation deemed necessary by the investigator or the sponsor, or access becomes available through another source such as but not limited to commercial availability, or a patient access program.

Drug: Talquetamab; Drug: Teclistamab

Part 2: Dose Expansion

EXPERIMENTAL

Participants will receive treatment doses (combination of tal+tec regimen) which will be determined by the recommended Phase 2 regimen (s) (RP2R\[s\]) of the study treatment identified in Part 1. Upon sponsor notification, participants will enter the LTE Phase or DA-LTE Phase and will continue to receive study treatment until disease progression, unacceptable toxicity, withdrawal of consent, discontinuation deemed necessary by the investigator or the sponsor, or access becomes available through another source such as but not limited to commercial availability, or a patient access program.

Drug: Talquetamab; Drug: Teclistamab

Part 3: Phase 2

EXPERIMENTAL

Participants will receive teclistamab + talquetamab combination therapy, at the RP2R selected from Part 1 and Part 2. Upon sponsor notification, participants will enter the LTE Phase or DA-LTE Phase and will continue to receive study treatment until disease progression, unacceptable toxicity, withdrawal of consent, discontinuation deemed necessary by the investigator or the sponsor, or access becomes available through another source such as but not limited to commercial availability, or a patient access program.

Drug: Talquetamab; Drug: Teclistamab

Interventions

Talquetamab DRUG

Talquetamab will be administered by subcutaneous (SC) injection.

Also known as: JNJ-64407564

Part 1: Dose Escalation; Part 2: Dose Expansion; Part 3: Phase 2

Teclistamab DRUG

Teclistamab will be administered by SC injection.

Also known as: JNJ-64007957

Part 1: Dose Escalation; Part 2: Dose Expansion; Part 3: Phase 2

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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (40)

University of Alabama at Birmingham, Comprehensive Cancer Center

Birmingham, Alabama, 35233, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University St. Louis School Medicine Siteman Cancer Center

St Louis, Missouri, 63108, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Atrium Health

Charlotte, North Carolina, 28204, United States

Location

Wake Forest University Baptist Medical Center (WFUBMC) - Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Oregon Health And Science University

Portland, Oregon, 97239, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

St Vincents Hospital Melbourne

Fitzroy, 3065, Australia

Location

Royal Perth Hospital

Perth, 6000, Australia

Location

Arthur J E Child Comprehensive Cancer Centre

Calgary, Alberta, T2N 5G2, Canada

Location

Alberta Health Services

Edmonton, Alberta, T6G 1Z2, Canada

Location

Princess Margaret Cancer Centre University Health Network

Toronto, Ontario, M5G 1X6, Canada

Location

McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

Location

Hadassah Medical Center

Jerusalem, 91120, Israel

Location

Sheba Medical Center

Ramat Gan, 52621, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

Kanazawa University Hospital

Kanazawa, 920-8641, Japan

Location

Nagoya City University Hospital

Nagoya, 467 8602, Japan

Location

Osaka University Hospital

Osaka, 565-0871, Japan

Location

Tohoku University Hospital

Sendai, 980 8574, Japan

Location

Japanese Red Cross Medical Center

Shibuya City, 150-8935, Japan

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

The Catholic University of Korea Seoul St Marys Hospital

Seoul, 06591, South Korea

Location

Hosp. Univ. Germans Trias I Pujol

Badalona, 08916, Spain

Location

Hosp Clinic de Barcelona

Barcelona, 08036, Spain

Location

Inst. Cat. Doncologia-H Duran I Reynals

L'Hospitalet de Llobregat, 08908, Spain

Location

Hosp Univ Fund Jimenez Diaz

Madrid, 28040, Spain

Location

UNIV. HOSP. October 12

Madrid, 28041, Spain

Location

Clinica Univ. de Navarra

Pamplona, 31008, Spain

Location

Hosp Clinico Univ de Salamanca

Salamanca, 37007, Spain

Location

Hosp. Univ. Marques de Valdecilla

Santander, 39008, Spain

Location

Related Publications (3)

• Kumar S, Mateos MV, Ye JC, Atrash S, Magen H, Quach H, Chu MP, Trudel S, Richter J, Rodriguez-Otero P, Chuah H, Gatt M, Medvedova E, Raza S, Yoon DH, Ishida T, Matous JV, Rosinol L, Onodera K, Scott E, Heuck C, Zhang J, Henninger T, O'Rourke L, Thakkar P, Festa M, Huang L, Zhou J, Takamoto M, Pei L, Lu J, Au N, Krevvata M, Usmani SZ, Cohen YC; RedirecTT-1 Investigators Study Group. Dual Targeting of Extramedullary Myeloma with Talquetamab and Teclistamab. N Engl J Med. 2026 Jan 1;394(1):51-61. doi: 10.1056/NEJMoa2514752. Epub 2025 Dec 7.

  PMID: 41358582 DERIVED

• Cohen YC, Magen H, Gatt M, Sebag M, Kim K, Min CK, Ocio EM, Yoon SS, Chu MP, Rodriguez-Otero P, Avivi I, Quijano Carde NA, Kumar A, Krevvata M, Peterson MR, Di Scala L, Scott E, Hilder B, Vanak J, Banerjee A, Oriol A, Morillo D, Mateos MV; RedirecTT-1 Investigators and Study Group. Talquetamab plus Teclistamab in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2025 Jan 9;392(2):138-149. doi: 10.1056/NEJMoa2406536.

  PMID: 39778168 DERIVED

• St Martin Y, Franz JK, Agha ME, Lazarus HM. Failure of CAR-T cell therapy in relapsed and refractory large cell lymphoma and multiple myeloma: An urgent unmet need. Blood Rev. 2023 Jul;60:101095. doi: 10.1016/j.blre.2023.101095. Epub 2023 Apr 29.

  PMID: 37173224 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

talquetamab

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: October 12, 2020
• First Posted: October 14, 2020
• Study Start: December 15, 2020
• Primary Completion: March 18, 2025
• Study Completion (Estimated): October 27, 2026
• Last Updated: January 16, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

US (13); AU (2); IL (3); JP (5); ES (8); CA (4); KR (5)