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

Multiple Myeloma Clinical Trial

— RedirecTT-1  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04586426
• Other study ID #: CR108901
• Secondary ID: 2019-004124-3864
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 15, 2020
• Est. completion date: August 29, 2025

Study information

• Verified date: June 2024
• Source: Janssen Research & Development, LLC
• Contact: Study Contact
• Phone: 844-434-4210
• Email: Participate-In-This-Study[@]its.jnj.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Recruiting
• Enrollment: 208
• Est. completion date: August 29, 2025
• Est. primary completion date: June 27, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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), Waldenstro¨m's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M- protein, and skin changes), or primary amyloid light chain amyloidosis

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Talquetamab
Talquetamab will be administered by subcutaneous (SC) injection.
• Teclistamab
Teclistamab will be administered by SC injection.
• Daratumumab
Daratumumab will be administered by SC injection.

Locations

Country	Name	City	State
Australia	St Vincents Hospital Melbourne	Fitzroy
Australia	Royal Perth Hospital	Perth
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Alberta Health Services	Edmonton	Alberta
Canada	McGill University Health Centre	Montreal	Quebec
Canada	Princess Margaret Cancer Centre University Health Network	Toronto	Ontario
Israel	Hadassah Medical Center	Jerusalem
Israel	Sheba Medical Center	Ramat Gan
Israel	Tel-Aviv Sourasky Medical Center	Tel-Aviv
Japan	Kanazawa University Hospital	Kanazawa
Japan	Nagoya City University Hospital	Nagoya
Japan	Osaka University Hospital	Osaka
Japan	Tohoku University Hospital	Sendai shi
Japan	Japanese Red Cross Medical Center	Shibuya
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul
Korea, Republic of	The Catholic University of Korea Seoul St. Mary's Hospital	Seoul
Spain	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
United States	Emory University	Atlanta	Georgia
United States	University of Alabama at Birmingham, Comprehensive Cancer Center	Birmingham	Alabama
United States	Atrium Health	Charlotte	North Carolina
United States	Cleveland Clinic	Cleveland	Ohio
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mount Sinai Medical Center	New York	New York
United States	Oregon Health And Science University	Portland	Oregon
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University in St. Louis	Saint Louis	Missouri
United States	Wake Forest University Baptist Medical Center (WFUBMC) - Comprehensive Cancer Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Israel,  Japan,  Korea, Republic of,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Secondary	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.	Approximately 5 years
Secondary	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.	Approximately 5 years
Secondary	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.	Approximately 5 years
Secondary	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.	Approximately 5 years
Secondary	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.	Approximately 5 years
Secondary	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.	Approximately 5 years
Secondary	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.	Approximately 5 years
Secondary	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.	Approximately 5 years
Secondary	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.	Approximately 5 years
Secondary	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.	Approximately 5 years
Secondary	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.	Approximately 5 years
Secondary	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.	Approximately 5 years
Secondary	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.	Approximately 5 years
Secondary	Part 3: Overall Survival (OS)	OS is measured from the date of first dose to the date of the participant's death.	Approximately 5 years
Secondary	Part 3: Number of Participants with Adverse Events	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.	Approximately 5 years
Secondary	Part 3: Number of Participants with Adverse Events 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