A Study of Ciltacabtagene Autoleucel and Talquetamab for the Treatment of Participants With High-Risk Multiple Myeloma (MonumenTAL-8)

Janssen (J&J Innovative Medicine)

Status and phase: Enrolling; Phase 2

Conditions: Multiple Myeloma

Treatments: Drug: Lenalidomide; Drug: Cilta-cel; Drug: Daratumumab; Drug: Talquetamab; Drug: Dexamethasone

Study type: Interventional

Funder types: Industry

Identifiers

NCT06550895

2023-507989-76 (EudraCT Number)

64407564MMY2008

2023-507989-76-00 (Registry Identifier)

Details and patient eligibility

About

The purpose of this study is to define the safety of Ciltacabtagene Autoleucel (Cilta-cel) and Talquetamab in participants with high-risk multiple myeloma (MM).

Enrollment: 30 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Documented diagnosis of MM according to the IMWG diagnostic criteria and is defined as a measurable disease at screening
• Cohorts 1 and 3: Received at least 3 prior lines of antimyeloma therapy and have undergone greater than or equal to (>=) 1 complete cycle of the therapy. Cohort 2: Be newly diagnosed MM and considered ineligible for high-dose chemotherapy with autologous stem cell transplant (ASCT)
• Cohorts 1 and 3: Documented evidence of progression of disease (PD) or failure to achieve a response to the last line of therapy
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• Participant of childbearing potential (POCBP) must have a negative pregnancy test using a highly sensitive β-human chorionic gonadotropin (hCG) serum pregnancy test at screening

Exclusion criteria

• Cohorts 1 and 3: Prior treatment with chimeric antigen receptor T cell (CAR-T) therapy directed at any target or any prior B cell maturation antigen (BCMA)-directed therapy/prior G protein-coupled receptor family C Group 5 member D (GPRC5D)-directed therapy. Cohort 2: Received any prior therapy for MM or smoldering myeloma other than a short course of corticosteroids
• Cohorts 1 and 3: Received either of the following: An allogenic stem cell transplant within 6 months before apheresis/first dose of study drug and no immunosuppressive medications administered before the start of study treatment. And secondly, received an autologous stem cell transplant less than (<)12 weeks before apheresis/first dose of study treatment
• Cohort 2: Received a strong cytochrome P450 (CYP450) inducer within 5 half-lives prior to daratumumab, lenalidomide and dexamethasone (DRd) induction therapy
• Receive live, attenuated vaccine within 4 weeks of enrollment
• Toxicity from previous anticancer therapy not resolved to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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30 participants in 3 patient groups

Cohort 1: Cilta-cel + Talquetamab Consolidation Post Chimeric Antigen Receptor T cell (CAR-T)Therapy

Experimental group

Description:

Participants with relapsed and/or refractory multiple myeloma (RRMM) will be administered Cilta-cel followed by multiple cycles of talquetamab consolidation treatment and will be followed up until death, lost to follow-up, consent withdrawal, or study end, whichever occurs first.

Treatment:

Drug: Talquetamab

Drug: Cilta-cel

Cohort 2: Cilta-cel + Talquetamab Consolidation Post CAR-T Therapy

Experimental group

Description:

Participants with newly diagnosed multiple myeloma (NDMM) will undergo daratummab, lenalidomide and dexamthasone (DRd) induction therapy followed by cilta-cel therapy and multiple cycles of talquetamab consolidation treatment and will be followed up until death, lost to follow-up, consent withdrawal, or study end, whichever occurs first.

Treatment:

Drug: Dexamethasone

Drug: Talquetamab

Drug: Daratumumab

Drug: Cilta-cel

Drug: Lenalidomide

Cohort 3: Tal Bridging Therapy Pre-CAR-T Therapy + Cilta-cel

Experimental group

Description:

Participants with RRMM will receive multiple cycles of talquetamab bridging therapy followed by cilta-cel therapy and will be followed up until death, lost to follow-up, consent withdrawal, or study end, whichever occurs first.

Treatment:

Drug: Talquetamab

Drug: Cilta-cel