A Study of the Combination of Talquetamab and Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma (RedirecTT-1)

Janssen (J&J Innovative Medicine)

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Multiple Myeloma

Treatments: Drug: Teclistamab; Drug: Talquetamab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04586426

CR108901

64007957MMY1003 (Other Identifier)

2019-004124-38 (EudraCT Number)

2023-503439-16-00 (Registry Identifier)

Details and patient eligibility

About

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).

Enrollment: 228 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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228 participants in 3 patient groups

Part 1: Dose Escalation

Experimental group

Description:

Participants will receive tec+tal in 28-day cycles following initial step-up doses. Upon sponsor notification, participants will enter the long-term extension (LTE) Phase or Drug-access Long-term Extension (DA-LTE) Phase and will continue to receive study treatment until disease progression, unacceptable toxicity, withdrawal of consent, discontinuation deemed necessary by the investigator or the sponsor, or access becomes available through another source such as but not limited to commercial availability, or a patient access program.

Treatment:

Drug: Teclistamab

Drug: Talquetamab

Part 2: Dose Expansion

Experimental group

Description:

Participants will receive treatment doses (combination of tal+tec regimen) which will be determined by the recommended Phase 2 regimen (s) (RP2R\[s\]) of the study treatment identified in Part 1. Upon sponsor notification, participants will enter the LTE Phase or DA-LTE Phase and will continue to receive study treatment until disease progression, unacceptable toxicity, withdrawal of consent, discontinuation deemed necessary by the investigator or the sponsor, or access becomes available through another source such as but not limited to commercial availability, or a patient access program.

Treatment:

Drug: Teclistamab

Drug: Talquetamab

Part 3: Phase 2

Experimental group

Description:

Participants will receive teclistamab + talquetamab combination therapy, at the RP2R selected from Part 1 and Part 2. Upon sponsor notification, participants will enter the LTE Phase or DA-LTE Phase and will continue to receive study treatment until disease progression, unacceptable toxicity, withdrawal of consent, discontinuation deemed necessary by the investigator or the sponsor, or access becomes available through another source such as but not limited to commercial availability, or a patient access program.

Treatment:

Drug: Teclistamab

Drug: Talquetamab