Multiple Myeloma
Conditions
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).
Interventions
DRUGTalquetamab
Talquetamab will be administered by subcutaneous (SC) injection.
DRUGTeclistamab
Teclistamab will be administered by SC injection.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants with Dose Limiting Toxicity (DLT) | Approximately 5 years 10 months | 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 1: Severity of DLT as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) | Approximately 5 years 10 months | 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 2: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability | Approximately 5 years 10 months | 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 10 months | 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 10 months | ORR is defined as the percentage of participants who have a partial response (PR) or better according Independent Review Committees (IRC). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 and Part 2: Number of Participants with Anti-Drug Antibodies to Daratumumab | Approximately 5 years 10 months | Number of participants with anti-drug antibodies to daratumumab will be assessed. |
| Part 1 and Part 2: Overall Response Rate (ORR) | Approximately 5 years 10 months | 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: Very Good Partial Response (VGPR) or Better Response Rate | Approximately 5 years 10 months | 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. |
| Parts 1, 2 and 3: Complete Response (CR) or Better Response Rate | Approximately 5 years 10 months | 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 10 months | sCR rate is defined as the percentage of participants who achieve a sCR according to the IMWG criteria. |
| Parts 1, 2 and 3: Serum Concentration of Talquetamab | Approximately 5 years 10 months | Serum samples will be analyzed to determine concentrations of talquetamab using a validated, specific, and sensitive immunoassay method. |
| Parts 1, 2 and 3: Time to Response | Approximately 5 years 10 months | 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 3: Progression free Survival (PFS) | Approximately 5 years 10 months | 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 10 months | 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 10 months | 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. |
| Part 3: Number of Participants with Adverse Events by Severity | Approximately 5 years 10 months | 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: Duration of Response (DOR) | Approximately 5 years 10 months | 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. |
| Parts 1, 2 and 3: Serum Concentration of Teclistamab | Approximately 5 years 10 months | Serum samples will be analyzed to determine concentrations of teclistamab using a validated, specific, and sensitive immunoassay method. |
| Part 1 and Part 2: Serum Concentration of Daratumumab | Approximately 5 years 10 months | Serum samples will be analyzed to determine concentrations of daratumumab 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 10 months | 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 10 months | Number of participants with anti-drug antibodies to teclistamab will be assessed. |
Countries
Australia, Canada, Israel, Japan, South Korea, Spain, United States
Outcome results
None listed