The purpose of this study is to evaluate the rate of response (how effectively treatment
is working) with signs of potential cure at 5 years after the start of induction
treatment. This is defined as a composite of sustained (at least 2 years) minimal
residual disease (MRD) negativity with complete response/stringent complete response
(CR/sCR) and a positron emission tomography/computed tomography (PET/CT) scan that does
not show any signs of cancer at 5 years. MRD negativity and CR/sCR is defined as no
detectable signs of remaining cancer cells after the treatment. This study will also
characterize how well the treatments administered work in the study through
progression-free survival (PFS). PFS is defined as the length of time during and after
the treatment of a disease, that a participant lives with the disease, but it does not
get worse.

A Study of Different Sequences of Cilta-cel, Talquetamab in Combination With Daratumumab and Teclistamab in Combination With Daratumumab Following Induction With Daratumumab, Bortezomib, Lenalidomide and Dexamethasone in Participants With Standard-risk Newly Diagnosed Multiple Myeloma

Multiple Myeloma

Kahler's Disease

Blood Cancer

Hematologic Neoplasms

Hematologic Malignancies

Hematology

Hematological Malignancies

Daratumumab

Bortezomib

Lenalidomide

Dexamethasone

Teclistamab

Cyclophosphamide

Talquetamab

Cilta-cel

Fludarabine

A Phase 2, Open-label Study to Evaluate the Efficacy and Safety of Different Sequences of Ciltacabtagene Autoleucel (Cilta-cel), Talquetamab SC in Combination With Daratumumab SC (Tal-D) and Teclistamab SC in Combination With Daratumumab SC (Tec-D) Following Induction With Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) in Participants With Standard-risk Newly Diagnosed Multiple Myeloma

Rate of Response with curative potential is defined as the percentage of participants
with a composite of durable (at least 2 years) minimal residual disease (MRD) (10^-5)
negativity with complete response/stringent complete response (CR/sCR) by serology and
negative positron emission tomography/computed tomography (PET/CT) imaging at 5-years
after start of induction therapy. This includes: negative imaging at 5-year landmark
time; MRD-negative status (at 10^-5) in 2 bone marrow examinations that are a minimum of
2 years apart; response of CR or better per the International Myeloma Working Group
(IMWG) criteria; no examination showing MRD-positive status or relapse from CR in between
assessments.

PFS is defined as the time from the date of randomization to either progressive disease
(PD), according to the IMWG response criteria, or death, whichever occurs first.

PFS is defined as the time from the date of randomization to either PD, according to the
IMWG response criteria, or death, whichever occurs first.

ORR (PR or better) is defined as the percentage of participants with best overall
response of PR or better according to IMWG response criteria.

Rate of CR or better is defined as the percentage of participants with best overall
response of CR or better according to IMWG response criteria.

Rate of VGPR or better is defined as the percentage of participants with best overall
response of VGPR or better rate according to IMWG response criteria.

DOR is calculated among responders (with a PR or better response) from the date of
initial documented response (PR or better) to the date of first documented evidence of PD
as defined according to IMWG criteria or death due to any cause, whichever occurs first.

Time to response (that is, time to first response) is defined as the time between the
date of randomization and the first efficacy evaluation that the participant has met all
criteria for PR or better based on the computerized algorithm per IMWG criteria for those
who had PR or better as their best response.

Duration of CR or better response is calculated among responders (with a CR or better
response) from the date of initial documented response CR or better to the date of first
documented evidence of PD as defined according to IMWG criteria or death due to any
cause, whichever occurs first.

Time to first CR or better response is defined as the time between the date of
randomization and the first efficacy evaluation that the participant has met all criteria
for CR or better based on the computerized algorithm per IMWG criteria.

PFS2 is defined as time from randomization to progression on the next line of therapy or
death, whichever comes first.

OS is measured from the date of randomization to the date of death due to any cause.

MRD-negative CR is defined as the percentage of participants who achieved both CR or
better and MRD negativity at a threshold of 10^-5 and 10^-6. MRD-negative CR rate will be
evaluated at the first occurrence from induction treatment initiation for participants
per IMWG criteria.

An Adverse event (AE) is any untoward medical occurrence in a participant participating
in a clinical study that does not necessarily have a causal relationship with the
pharmaceutical/ biological agent under study. TEAEs are defined as AEs with onset or
worsening on or after date of first dose of study treatment. Severity of TEAEs 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 events.

Change from baseline in participants' HRQoL (symptoms and functioning) as assessed by
EORTC-QLQ-C30 will be reported. The EORTC-QLQ-C30 includes 30 items in 5 functional
scales (physical, role, emotional, cognitive, social), 1 global health status scale, 3
symptom scales (pain, fatigue, nausea/vomiting), and 6 single symptom items (dyspnea,
insomnia, appetite loss, constipation, diarrhea, financial difficulties). The recall
period is 1 week ("past week") and responses are reported using a verbal rating scale.
The item and scale scores are transformed to a 0-to-100 scale. A higher score represents
greater HRQoL, better functioning, and more (worse) symptoms.

Participants will undergo apheresis followed by 4 cycles of DVRd induction (each cycle is
of 28 days) and cilta-cel will be generated from the participants' T-cells selected from
the apheresis product. Upon completion of cilta-cel production, product release, and
completion of induction, participants will begin consolidation with 4 cycles of Tal-D
(each cycle is of 28 days), followed by a conditioning regimen (cyclophosphamide and
fludarabine daily for 3 days); cilta-cel will be administered 5 to 7 days after the start
of the conditioning regimen.

Participants will undergo apheresis followed by 4 cycles of DVRd induction and Cilta-cel
will be generated from the participants' T-cells selected from the apheresis product.
Upon completion of cilta-cel production, product release and completion of induction,
participants will begin consolidation with a conditioning regimen (cyclophosphamide and
fludarabine daily for 3 days) with infusion of cilta-cel 5 to 7 days after the start of
the conditioning regimen. Following cilta-cel infusion, alternating cycles of Tal-D
(Cycle 1, 3, 5, and 7) and Tec-D (Cycle 2, 4, 6, and 8) will be started, no earlier than
Day 84 and no later than Day 168 post cilta-cel infusion. Each cycle of Tal-D or Tec-D is
84 days which includes an extended treatment-free interval.

A Study of Different Sequences of Cilta-cel, Talquetamab in Combination With Daratumumab and Teclistamab in Combination With Daratumumab Following Induction With Daratumumab, Bortezomib, Lenalidomide and Dexamethasone in Participants With Standard-risk Newly Diagnosed Multiple Myeloma

Trials at a glance

Trials at a glance