Clinical trial NCT04586426: A Study of the Combination of Talquetamab and Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2020-10-14
Enrollment: 228
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Part 1: Number of Participants with Dose Limiting Toxicity (DLT)
timeFrame: Approximately 5 years
measure: Part 1: Severity of DLT as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)
timeFrame: Approximately 5 years
measure: Part 2: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability
timeFrame: Approximately 5 years
measure: Part 2: Number of Participants with Adverse Events and SAEs by Severity
timeFrame: Approximately 5 years
measure: Part 3: Overall Response Rate (ORR)
timeFrame: Approximately 5 years
Secondary outcomes:
measure: Parts 1, 2 and 3: Serum Concentration of Talquetamab
timeFrame: Approximately 5 years
measure: Parts 1, 2 and 3: Serum Concentration of Teclistamab
timeFrame: Approximately 5 years
measure: Part 1 and Part 2: Serum Concentration of Daratumumab
timeFrame: Approximately 5 years
measure: Parts 1, 2 and 3: Number of Participants with Anti-Drug Antibodies to Talquetamab
timeFrame: Approximately 5 years
measure: Parts 1, 2 and 3: Number of Participants with Anti-Drug Antibodies to Teclistamab
timeFrame: Approximately 5 years
measure: Part 1 and Part 2: Number of Participants with Anti-Drug Antibodies to Daratumumab
timeFrame: Approximately 5 years
measure: Part 1 and Part 2: Overall Response Rate (ORR)
timeFrame: Approximately 5 years
measure: Parts 1, 2 and 3: Very Good Partial Response (VGPR) or Better Response Rate
timeFrame: Approximately 5 years
measure: Parts 1, 2 and 3: Complete Response (CR) or Better Response Rate
timeFrame: Approximately 5 years
measure: Part 1, 2 and 3: Stringent Complete Response (sCR) Rate
timeFrame: Approximately 5 years
measure: Parts 1, 2 and 3: Duration of Response (DOR)
timeFrame: Approximately 5 years
measure: Parts 1, 2 and 3: Time to Response
timeFrame: Approximately 5 years
measure: Part 3: Progression free Survival (PFS)
timeFrame: Approximately 5 years
measure: Part 3: Overall Survival (OS)
timeFrame: Approximately 5 years
measure: Part 3: Number of Participants with Adverse Events
timeFrame: Approximately 5 years
measure: Part 3: Number of Participants with Adverse Events by Severity
timeFrame: Approximately 5 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham, Comprehensive Cancer Center
state: Alabama
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University St. Louis School Medicine Siteman Cancer Center
state: Missouri
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Charlotte
country: United States
facility: Atrium Health
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Medical Center (WFUBMC) - Comprehensive Cancer Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Oregon Health And Science University
state: Oregon
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Fitzroy
country: Australia
facility: St Vincents Hospital Melbourne
city: Perth
country: Australia
facility: Royal Perth Hospital
city: Calgary
country: Canada
facility: Arthur J E Child Comprehensive Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Alberta Health Services
state: Alberta
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre University Health Network
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Tel-Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Kanazawa
country: Japan
facility: Kanazawa University Hospital
city: Nagoya
country: Japan
facility: Nagoya City University Hospital
city: Osaka
country: Japan
facility: Osaka University Hospital
city: Sendai shi
country: Japan
facility: Tohoku University Hospital
city: Shibuya
country: Japan
facility: Japanese Red Cross Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Seoul St Marys Hospital
city: Badalona
country: Spain
facility: Hosp. Univ. Germans Trias I Pujol
city: Barcelona
country: Spain
facility: Hosp Clinic de Barcelona
city: L Hospitalet De Llobregat
country: Spain
facility: Inst. Cat. Doncologia-H Duran I Reynals
city: Madrid
country: Spain
facility: Hosp Univ Fund Jimenez Diaz
city: Madrid
country: Spain
facility: UNIV. HOSP. October 12
city: Pamplona
country: Spain
facility: Clinica Univ. de Navarra
city: Salamanca
country: Spain
facility: Hosp Clinico Univ de Salamanca
city: Santander
country: Spain
facility: Hosp. Univ. Marques de Valdecilla
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: