A Phase 3 Randomized Study Comparing Teclistamab in Combination with Daratumumab SC
and Lenalidomide (Tec-DR) and Talquetamab in Combination with Daratumumab SC and
Lenalidomide (Tal-DR) versus Daratumumab SC, Lenalidomide, and Dexamethasone (DRd) in
Participants with Newly Diagnosed Multiple Myeloma Who are Either Ineligible or not Intended
for Autologous Stem Cell Transplant as Initial Therapy

Primary Outcome Measure:

1. Progression Free Survival (PFS) from randomization to the date of disease

progression or death (Up to 9 years). PFS is defined as the duration from the

date of randomization to either progressive disease or death, whichever comes

first. Disease progression will be determined according to the International

Myeloma Working Group (IMWG) response criteria.

2. Complete Response (CR) or Better. From randomization up to 9 years. CR or

better is defined as the percentage of participants achieving CR or stringent

complete response (sCR) prior to subsequent antimyeloma therapy in accordance

with the IMWG criteria during or after the study treatment.

1. Very Good Partial Response (VGPR) or Better. Timeframe: From randomization

up to 9 years. VGPR or better is defined as the percentage of participants

achieving VGPR and CR (including stringent complete response [sCR]) prior to

subsequent antimyeloma therapy in accordance with the International Myeloma

Working Group (IMWG) criteria during or after the study treatment.

2. Sustained Minimal Residual disease (MRD)-negative Complete Response (CR).

From randomization up to 9 years. Sustained MRD-negative CR is defined as

participants with CR or better who sustain MRD-negative status, as determined

by next-generation sequencing (NGS) with sensitivity of 10^-5, for at least 12

months

without any examination showing MRD positive status or progressive disease in

between.

3. MRD-negative CR. Timeframe: From randomization up to 9 years. MRD-negative

CR is defined as the percentage of participants who achieve MRD-negative

status, as determined by NGS with sensitivity of 10^-5, at any time after

randomization and prior to progressive disease or subsequent antimyeloma

therapy and who achieve CR or better.

4. Progression Free Survival on Next-line Therapy (PFS2). Timeframe: From

randomization up to 9 years. PFS2 is defined as the time interval between the

date of randomization and date of event, which is defined as progressive

disease as assessed by investigator that starts after the next line of

subsequent therapy, or death from any cause, whichever occurs first.

5. Overall Survival (OS). Timeframe: From randomization to the date of death

(up to 9 years). OS is defined as the time from the date of randomization to

the date of death due to any cause.

6. Number of Participants with Adverse Events (AEs) by Severity. Timeframe:

From randomization up to 9 years. An adverse event is any untoward medical

occurrence in a clinical study participant administered a pharmaceutical

(investigational or non-investigational) product. An adverse event does not

necessarily have a causal relationship with the treatment. Severity 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, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening, and Grade

5: death related to adverse event.

7. Number of Participants with Abnormalities in Laboratory Parameters.

Timeframe: From randomization up to 9 years. Number of participants with

abnormalities in laboratory parameters (serum chemistry and hematology) will be

reported.

8. Number of Participants with Abnormalities in Vital Signs. Timeframe: From

randomization up to 9 years. Number of participants with abnormalities in vital

signs (temperature, pulse/heart rate, respiratory rate, blood pressure) will be

reported.

9. Number of Participants with Abnormalities in Physical Examination.

Timeframe: From randomization up to 9 years. Number of participants with

abnormalities in physical examination will be reported.

10.. Number of Participants with Abnormalities in Electrocardiogram (ECG).

Timeframe: From randomization up to 9 years. Number of participants with

abnormalities in ECG will be reported.

11. Serum Concentrations of Teclistamab and Talquetamab. Timeframe: From

randomization up to 9 years. Serum samples will be analyzed to determine

concentrations of teclistamab using validated, specific, and sensitive methods.

12. Number of Participants with Anti-drug Antibodies (ADAs) to Teclistamab and

Talquetamab: Timeframe: From randomization up to 9 years. Number of

participants with ADAs to teclistamab will be reported.

13. Change from Baseline in Symptoms, Functioning, and Health-related Quality

of Life (HRQoL) as Assessed by European Organization for Research and Treatment

of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30). Timeframe:

From baseline up to 9 years. The EORTC-QLQ-C30 Version 3 includes 30 items that

make up 5 functional scales (physical, role, emotional, cognitive, and social),

1 global health status scale, 3 symptom scales (pain, fatigue, and

nausea/vomiting), and 5 single symptom items (dyspnea, insomnia, appetite loss,

constipation, and diarrhea) and a single impact item (financial difficulties).

The recall period is 7 days (*past week*), and responses are reported using a

verbal and numeric rating scales. The item and scale scores are transformed to

a 0 to 100 scale. A high scale score represents a higher response level. Thus,

a high score for a functional scale represents a high/healthy level of

functioning and a high score for the global health status represents high

HRQoL, but a high score for a symptom scale/item represents a high level of

symptomatology/problems.

14. Change from Baseline in Treatment-related Symptoms as Assessed by

Patient-Reported Outcomes Version of the Common Terminology Criteria for

Adverse Events (PRO-CTCAE). Timeframe: Baseline through Cycle 6 (each cycle

of28 days) (up to 196 days). The National Cancer Institute's (NCI's) PRO-CTCAE

is an item library of common AEs experienced by people with cancer that are

appropriate for self-reporting of treatment tolerability. Each symptom selected

for inclusion can be rated by up to 3 attributes characterizing the

presence/frequency, severity, and/or interference of the AEs. It ranges from 0

to 4 with higher scores indicating higher frequency or greater severity/impact.

15. Change from Baseline in Symptoms, Functioning, and Overall HRQoL as

Assessed by EuroQol Five Dimension Questionnaire 5-Level (EQ-5D-5L). Timeframe:

From baseline up to 9 years. The EQ-5D-5L is a 5-item questionnaire that

assesses 5 domains including mobility, self-care, usual activities,

pain/discomfort, and anxiety/depression plus a visual analog scale rating

*health today* with anchors ranging from 0 (worst imaginable health state) to

100 (best imaginable health state).

16. Time to Sustained Worsening in Symptoms, Functioning, and HRQoL: Timeframe:

From randomization up to 9 years. Time to sustained worsening in symptoms,

functioning and HRQoL is defined as the interval from the date of randomization

to the start date of meaningful change.