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

Phase 2Active Not RecruitingNCT04586426

Janssen Research & Development, LLC228 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

228

Conditions

Multiple Myeloma

Interventions

TalquetamabDRUG

Talquetamab will be administered by subcutaneous (SC) injection.

TeclistamabDRUG

Teclistamab will be administered by SC injection.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (40)

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: Approximately 5 years 10 months

Part 2: Number of Participants with Adverse Events and SAEs by Severity

Time frame: Approximately 5 years 10 months

Part 3: Overall Response Rate (ORR)

Data from ClinicalTrials.gov

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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

St 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

...and 30 more locations

Secondary Outcomes

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.

Time frame: Approximately 5 years 10 months

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.

Time frame: Approximately 5 years 10 months

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.

Time frame: Approximately 5 years 10 months

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.

Time frame: Approximately 5 years 10 months

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.

Time frame: Approximately 5 years 10 months

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.

Time frame: Approximately 5 years 10 months

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.

Time frame: Approximately 5 years 10 months

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.

Time frame: Approximately 5 years 10 months

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.

Time frame: Approximately 5 years 10 months

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.

Time frame: Approximately 5 years 10 months

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.

Time frame: Approximately 5 years 10 months

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.

Time frame: Approximately 5 years 10 months

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.

Time frame: Approximately 5 years 10 months

Part 3: Overall Survival (OS)

OS is measured from the date of first dose to the date of the participant's death.

Time frame: Approximately 5 years 10 months

Part 3: Number of Participants with Adverse Events

Time frame: Approximately 5 years 10 months

Part 3: Number of Participants with Adverse Events by Severity

Time frame: Approximately 5 years 10 months