A Study Comparing Anitocabtagene Autoleucel to Standard of Care Therapy in Participants With Relapsed/ Refractory Multiple Myeloma

After completing the treatment period, all participants who will receive anitocabtagene autoleucel, will be followed in the post-treatment follow-up period. Thereafter, participants will transition to a separate long-term follow-up study (KT-US-982-5968) to continue follow-up out to 15 years.

Primary Outcome Measures

1. Progression-Free Survival (PFS)
   PFS is defined as the time from randomization to disease progression per International Myeloma Working Group (IMWG) criteria as determined by independent review committee (IRC), or death due to any cause, whichever occurs first.
2. Minimal Residual Disease (MRD) Complete Response (CR) Rate at 9 Months
   Minimal MRD is defined as the proportion of participants achieving CR/stringent CR (sCR) and MRD-negative status at 9 months. MRD negativity at 9 months is defined as negative MRD value at 9 months (± 3 months) in bone marrow assessment (\< 1 in 105 nucleated cells per IMWG criteria using NGS) (Kumar 2016). CR/sCR per IMWG criteria is determined by IRC.

Secondary Outcome Measures

1. CR Rate (CR/ Stringent Complete Response (sCR))
   CR rate is defined as the proportion of participants who achieved a best overall response of CR or sCR per IMWG criteria as determined by IRC.
2. Overall MRD Negativity
   Overall MRD negativity, defined as the proportion of any MRD negativity in participants with bone marrow aspirate (\< 1 in 10\^5 nucleated cells per IMWG criteria using next-generation sequencing (NGS)) at any time after randomization until disease progression, subsequent anti-multiple myeloma (MM) therapy, or death.
3. Overall survival (OS)
   OS is defined as the time from randomization to death due to any cause.
4. Overall Response Rate (ORR)
   ORR is defined as the proportion of participants who achieve a best overall response of at least partial response (PR) or better (sCR, CR, very good partial response (VGPR), or PR) per IMWG criteria.
5. MRD-negative CR/sCR
   MRD-negative CR/sCR is defined as the proportion of participants achieving MRD-negative CR/sCR until disease progression, subsequent anti-MM therapy, or death.
6. MRD-negative VGPR+
   MRD-negative VGPR+ is defined as the proportion of participants achieving MRD negativity and sCR/CR/VGPR until disease progression, subsequent anti-MM therapy, or death.
7. Sustained MRD Negativity
   Sustained MRD negativity is defined as the proportion of participants remaining MRD-negative at the 10\^-5 sensitivity threshold for the specified number of months starting from the first MRD-negative assessment date to the last MRD-negative assessment date prior to disease progression, subsequent anti-MM therapy, or death. Duration may include ≥ 12 months. Sustained MRD negativity will be evaluated for overall MRD negativity, MRD-negative CR/sCR, and MRD-negative VGPR+.
8. Duration of Response (DOR)
   DOR is derived only among participants who experience an overall response (sCR, CR, VGPR, or PR) per IMWG criteria and is defined as the time from first overall response to disease progression per IMWG criteria, or death from any cause, whichever occurs first.
9. Time to Progression
   Time to progression is defined as the time from randomization to the first documented disease progression per IMWG criteria, or death due to disease progression, whichever occurs first.
10. Time to Next Treatment
    Time to next treatment is defined as the time from randomization to the start of subsequent anti-MM therapy or death from any cause, whichever occurs first.
11. Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
12. Percentage of Participants With Anti-Anitocabtagene Autoleucel CAR Antibodies (Anitocabtagene Autoleucel Arm)
13. Percentage of Participants With Presence of Replication-Competent Lentivirus (Anitocabtagene Autoleucel Arm)
14. Change From Baseline in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score
    The EORTC-QLQ-C30 is a multi-item questionnaire measuring the following content: five (5) multi-item functional scales, three (3) multi-item symptom scales, six (6) single item symptoms scales, one (1) global health status scale, and one (1) global health-related quality of life (HRQoL). Each scale is measured from 0 to 100 after a linear transformation. Higher scores for functioning scales and for the Global Health Status or Global HRQoL scales indicate a higher level of functioning and a better HRQoL respectively, whereas higher scores in symptom scales represent a high level of symptoms.
15. Change From Baseline in the EORTC - Multiple Myeloma Module (EORTC QLQ-MY20) Score
    The EORTC QLQ-MY20 has 20 items across 4 independent subscales; 2 functional subscales (body image, future perspective), and 2 symptoms scales (disease symptoms, and side effects of treatment) with a recall period of one week. Scores from each subscale are transformed from 0 to 100. For the functional scales, high scores represent improvement. For the symptom scales, higher scores represent worsening.
16. Change From Baseline in the European Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L) Score
    The EQ-5D-5L questionnaire is a generic measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L comprises 2 components: a questionnaire covering 5 dimensions and a tariff of values based upon direct valuations of health states using a visual analog scale (VAS). The total score for EQ-5D-5L index is presented on a range where higher scores indicate better outcome. A positive change from Baseline indicates improvement.
17. Percentage of Participants Using Healthcare Resources
    Healthcare resource utilization will be assessed based on the numbers of hospitalizations, intensive care unit (ICU) inpatient days, and non-ICU inpatient days.