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

Registration Number
NCT06550895
Lead Sponsor
Janssen Research & Development, LLC
Brief Summary

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).

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
30
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
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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
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Cohort 2: Cilta-cel + Talquetamab Consolidation Post CAR-T TherapyCilta-celParticipants 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.
Cohort 1: Cilta-cel + Talquetamab Consolidation Post Chimeric Antigen Receptor T cell (CAR-T)TherapyCilta-celParticipants 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.
Cohort 1: Cilta-cel + Talquetamab Consolidation Post Chimeric Antigen Receptor T cell (CAR-T)TherapyTalquetamabParticipants 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.
Cohort 3: Tal Bridging Therapy Pre-CAR-T Therapy + Cilta-celCilta-celParticipants 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.
Cohort 2: Cilta-cel + Talquetamab Consolidation Post CAR-T TherapyDaratumumabParticipants 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.
Cohort 2: Cilta-cel + Talquetamab Consolidation Post CAR-T TherapyTalquetamabParticipants 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.
Cohort 2: Cilta-cel + Talquetamab Consolidation Post CAR-T TherapyLenalidomideParticipants 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.
Cohort 2: Cilta-cel + Talquetamab Consolidation Post CAR-T TherapyDexamethasoneParticipants 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.
Cohort 3: Tal Bridging Therapy Pre-CAR-T Therapy + Cilta-celTalquetamabParticipants 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.
Primary Outcome Measures
NameTimeMethod
Number of Participants With Adverse Events (AE) by Severity According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0Up to 3 years and 5 months

An AE is any untoward medical occurrence in a participant administered a pharmaceutical (investigational or non-investigational) product. It does not necessarily have a causal relationship with the investigational product. The severity of AEs has 5 grades based on NCI-CTCAE version 5.0 criteria: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Lif...

Secondary Outcome Measures
NameTimeMethod
Overall SurvivalUp to 3 years and 5 months

Overall Survival is measured from the date of the first study treatment to the date of the participant's death.

Percentage of Participants with Minimal Residual Disease (MRD) NegativityUp to 3 years and 5 months

The percentage of participants who achieve MRD-negativity at a threshold of 10\^-5 at any timepoint after the date of the first study treatment and before disease progression or start of any subsequent antimyeloma therapy will be reported.

Percentage of Participants with Sustained MRD-NegativityUp to 3 years and 5 months

The percentage of participants who sustained MRD-negative status, as determined by next generation sequencing (NGS) with sensitivity of 10\^-5, for at least 6 months without examination showing MRD-positive or PD in between will be reported.

Percentage of Participants With Overall Response (OR)Up to 3 years and 5 months

The percentage of participants who have a partial response (PR) or better response according to the International Myeloma Working Group (IMWG) response criteria will be reported.

Percentage of Participants with Very Good Partial Response (VGPR) or BetterUp to 3 years and 5 months

The percentage of participants who achieve a VGPR or better response according to the IMWG response criteria will be reported.

Percentage of Participants with Complete Response (CR) or Stringent Complete Response (sCR)Up to 3 years and 5 months

The percentage of participants with best overall response of CR or sCR will be reported according to IMWG criteria.

Duration of Response (DOR)Up to 3 years and 5 months

DOR is defined as the time from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease (PD) (defined in the IMWG response criteria) or death due to any cause, whichever occur first.

Time to Response (TTR)Upto 3 years and 5 months

TTR is defined as the time between date of the first study treatment and the first efficacy evaluation that the participant met all criteria for PR or better.

Progression Free Survival (PFS)Up to 3 years and 5 months

PFS is defined as the time from the date of the first study treatment to the date of first documented disease progression (defined in the IMWG response criteria), or death due to any cause, whichever occurs first.

Trial Locations

Locations (12)

University of Pennsylvania

🇺🇸

Philadelphia, Pennsylvania, United States

University of Iowa Hospital and Clinics

🇺🇸

Iowa City, Iowa, United States

Norton Cancer Institute

🇺🇸

Louisville, Kentucky, United States

Barbara Ann Karmanos Cancer Institute

🇺🇸

Detroit, Michigan, United States

Icahn School of Medicine at Mount Sinai

🇺🇸

New York, New York, United States

Memorial Sloan Kettering Cancer Center

🇺🇸

New York, New York, United States

Thomas Jefferson University

🇺🇸

Philadelphia, Pennsylvania, United States

Medical College Of Wisconsin

🇺🇸

Milwaukee, Wisconsin, United States

Royal Prince Alfred Hospital

🇦🇺

Camperdown, Australia

Austin Hospital

🇦🇺

Heidelberg, Australia

Peter MacCallum Cancer Centre

🇦🇺

Melbourne, Australia

The Alfred Hospital

🇦🇺

Melbourne, Australia

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