A Study of the Combination of Talquetamab and Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT04586426
- Lead Sponsor
- Janssen Research & Development, LLC
- 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).
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 228
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 2: Dose Expansion Talquetamab 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. Part 1: Dose Escalation Teclistamab Participants will receive tec+tal with or without daratumumab in 28-day cycles following initial step-up doses. Part 1: Dose Escalation Daratumumab Participants will receive tec+tal with or without daratumumab in 28-day cycles following initial step-up doses. Part 3: Phase 2 Teclistamab Participants will receive teclistamab + talquetamab combination therapy, at the RP2R selected from Part 1 and Part 2. Part 1: Dose Escalation Talquetamab Participants will receive tec+tal with or without daratumumab in 28-day cycles following initial step-up doses. Part 2: Dose Expansion Teclistamab 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. Part 2: Dose Expansion Daratumumab 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. Part 3: Phase 2 Talquetamab Participants will receive teclistamab + talquetamab combination therapy, at the RP2R selected from Part 1 and Part 2.
- Primary Outcome Measures
Name Time Method Part 1: Severity of DLT as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Approximately 5 years 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.
Part 1: Number of Participants with Dose Limiting Toxicity (DLT) Approximately 5 years 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.
Part 2: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability Approximately 5 years 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.
Part 2: Number of Participants with Adverse Events and SAEs by Severity Approximately 5 years 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.
Part 3: Overall Response Rate (ORR) Approximately 5 years ORR is defined as the percentage of participants who have a partial response (PR) or better according Independent Review Committees (IRC).
- Secondary Outcome Measures
Name Time Method Part 1 and Part 2: Overall Response Rate (ORR) Approximately 5 years 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.
Parts 1, 2 and 3: Time to Response Approximately 5 years 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.
Part 1 and Part 2: Serum Concentration of Daratumumab Approximately 5 years Serum samples will be analyzed to determine concentrations of daratumumab using a validated, specific, and sensitive immunoassay method.
Part 1 and Part 2: Number of Participants with Anti-Drug Antibodies to Daratumumab Approximately 5 years Number of participants with anti-drug antibodies to daratumumab will be assessed.
Parts 1, 2 and 3: Very Good Partial Response (VGPR) or Better Response Rate Approximately 5 years 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.
Part 3: Number of Participants with Adverse Events by Severity Approximately 5 years 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.
Parts 1, 2 and 3: Complete Response (CR) or Better Response Rate Approximately 5 years 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.
Part 1, 2 and 3: Stringent Complete Response (sCR) Rate Approximately 5 years sCR rate is defined as the percentage of participants who achieve a sCR according to the IMWG criteria.
Part 3: Progression free Survival (PFS) Approximately 5 years 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.
Part 3: Overall Survival (OS) Approximately 5 years OS is measured from the date of first dose to the date of the participant's death.
Part 3: Number of Participants with Adverse Events Approximately 5 years 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.
Parts 1, 2 and 3: Serum Concentration of Talquetamab Approximately 5 years Serum samples will be analyzed to determine concentrations of talquetamab using a validated, specific, and sensitive immunoassay method.
Parts 1, 2 and 3: Serum Concentration of Teclistamab Approximately 5 years Serum samples will be analyzed to determine concentrations of teclistamab using a validated, specific, and sensitive immunoassay method.
Parts 1, 2 and 3: Number of Participants with Anti-Drug Antibodies to Talquetamab Approximately 5 years Number of participants with anti-drug antibodies to talquetamab will be assessed.
Parts 1, 2 and 3: Number of Participants with Anti-Drug Antibodies to Teclistamab Approximately 5 years Number of participants with anti-drug antibodies to teclistamab will be assessed.
Parts 1, 2 and 3: Duration of Response (DOR) Approximately 5 years 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.
Trial Locations
- Locations (40)
Arthur J E Child Comprehensive Cancer Centre
🇨🇦Calgary, Alberta, Canada
University of Alabama at Birmingham, Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Colorado Blood Cancer Institute
🇺🇸Denver, Colorado, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Washington University St. Louis School Medicine Siteman Cancer Center
🇺🇸Saint Louis, Missouri, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Atrium Health
🇺🇸Charlotte, North Carolina, United States
Wake Forest University Baptist Medical Center (WFUBMC) - Comprehensive Cancer Center
🇺🇸Winston-Salem, North Carolina, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Oregon Health And Science University
🇺🇸Portland, Oregon, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
St Vincents Hospital Melbourne
🇦🇺Fitzroy, Australia
Royal Perth Hospital
🇦🇺Perth, Australia
Alberta Health Services
🇨🇦Edmonton, Alberta, Canada
Princess Margaret Cancer Centre University Health Network
🇨🇦Toronto, Ontario, Canada
McGill University Health Centre
🇨🇦Montreal, Quebec, Canada
Hadassah Medical Center
🇮🇱Jerusalem, Israel
Sheba Medical Center
🇮🇱Ramat Gan, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel-Aviv, Israel
Nagoya City University Hospital
🇯🇵Nagoya, Japan
Kanazawa University Hospital
🇯🇵Kanazawa, Japan
Osaka University Hospital
🇯🇵Osaka, Japan
Tohoku University Hospital
🇯🇵Sendai shi, Japan
Japanese Red Cross Medical Center
🇯🇵Shibuya, Japan
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea Seoul St Marys Hospital
🇰🇷Seoul, Korea, Republic of
Hosp. Univ. Germans Trias I Pujol
🇪🇸Badalona, Spain
Hosp Clinic de Barcelona
🇪🇸Barcelona, Spain
Inst. Cat. Doncologia-H Duran I Reynals
🇪🇸L Hospitalet De Llobregat, Spain
Hosp Univ Fund Jimenez Diaz
🇪🇸Madrid, Spain
UNIV. HOSP. October 12
🇪🇸Madrid, Spain
Clinica Univ. de Navarra
🇪🇸Pamplona, Spain
Hosp Clinico Univ de Salamanca
🇪🇸Salamanca, Spain
Hosp. Univ. Marques de Valdecilla
🇪🇸Santander, Spain