Phase 3 Study of Teclistamab in Combination With Lenalidomide and Teclistamab Alone Versus Lenalidomide Alone in Participants With Newly Diagnosed Multiple Myeloma as Maintenance Therapy Following Autologous Stem Cell Transplantation

Study Overview
=================
Brief Summary
-----------------
This is a multicenter, randomized, open-label, Phase 3 study in participants with newly diagnosed multiple myeloma to evaluate the benefits of teclistamab in combination with lenalidomide and teclistamab alone versus lenalidomide alone as maintenance therapy after autologous stem cell transplant.

Official Title
-----------------
Phase 3 Study of Teclistamab in Combination With Lenalidomide and Teclistamab Alone Versus Lenalidomide Alone in Participants With Newly Diagnosed Multiple Myeloma as Maintenance Therapy Following Autologous Stem Cell Transplantation - MajesTEC-4

Conditions
-----------------
Multiple Myeloma

Intervention / Treatment
-----------------
* Drug: Teclistamab
* Drug: Lenalidomide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Must have a new diagnosis of multiple myeloma according to IMWG criteria and have received induction +/- consolidation. Must have received only one line of therapy and achieved at least a partial response (≥PR) as per IMWG 2016 response criteria (Kumar 2016) without evidence of progression at the time of first treatment dose. Must not be intolerant to the starting dose of lenalidomide. Must not have received any maintenance therapy. Have an ECOG performance status score of 0, 1, or 2 at screening and immediately prior to the start of administration of study treatment Have clinical laboratory values within prespecified range. Exclusion Criteria: Received any prior BCMA-directed therapy. Any previous therapy with an immune cell redirecting agent or gene modified adoptive cell therapy (eg, chimeric antigen receptor modified T cells, NK cells). Discontinued treatment due to any AE related to lenalidomide as determined by the investigator. Progressed on multiple myeloma therapy at any time prior to screening. Received a cumulative dose of corticosteroids equivalent to ≥140 mg of prednisone within the 14 days prior to first treatment dose. Received a live, attenuated vaccine within 4 weeks before first treatment dose. Non-live vaccines or non-replicating authorized for emergency use (eg. COVID-19) are allowed.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Teclistamab-Lenalidomide (Tec-Len)<br>Teclistamab will be administered via a subcutaneous injection (SC) | Drug: Teclistamab<br>* Teclistamab will be administered via a subcutaneous injection (SC)<br>* Other names: JNJ-64007957;Drug: Lenalidomide<br>* Lenalidomide will be administered orally<br>|
| Active Comparator: Arm B Lenalidomide Alone (Len)<br>Lenalidomide orally. | Drug: Lenalidomide<br>* Lenalidomide will be administered orally<br>|
| Experimental: Arm C Teclistamab-Alone (Tec)<br>Teclistamab will be administered via a subcutaneous injection (SC) | Drug: Teclistamab<br>* Teclistamab will be administered via a subcutaneous injection (SC)<br>* Other names: JNJ-64007957;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS is defined as the time from the date of randomization to the date of disease progression (as assessed by IMWG criteria) or death due to any cause, whichever occurs first. | from randomization to the date of disease progression or death (approximately up to 8 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of efficacy | Efficacy, assessed by rate of CR or better, MRD negative CR, sustained MRD negativity, CR and MRD negative conversion PFS after next line of therapy (PFS2), time to next treatment (TTNT), OS and also safety, PK and immunogenicity | from randomization to the date of disease progression or death (approximately up to 8 years) | 
| Overall Survival (OS) | Overall Survival (OS), measured from the date of from randomization to the date the subject's death | from the date of from randomization to the date the subject's death, assessed up to 8 years] | 
| Change in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core module (EORTC QLQ-C30) score and the difference between-treatment arms | The EORTC QLQ-C30 is a 30-item questionnaire containing both single and multi-item measures. These include five functional scales (Physical, Role, Cognitive, Emotional, and Social Functioning), three symptom scales (Fatigue, Pain, and Nausea/Vomiting), a Global Health Status/ Quality-of-Life (QoL) scale, and six single items (Constipation, Diarrhea, Insomnia, Dyspnea, Appetite Loss, and Financial Difficulties). The scores ranges from 0-100, a high score for functional scales and for Global Health Status/QoL represent better functioning ability or Health-Related Quality-of-Life (HRQoL), whereas a high score for symptom scales and single items represents significant symptomatology. | baseline up to 8 years | 
| EQ-5D-5L health utility values and the difference between-treatment arms | 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 | baseline up to 8 years | 
| MySIm-Q Symptom and Impacts in Patients With Multiple Myeloma and the difference between treatment arms | The MySIm-Q is a disease-specific PRO assessment complementary to the EORTC-QLQ-C30. It includes 17 items resulting in a symptom subscale and an impact subscale. The recall period is the past 7 days, and responses are reported on a 5-point verbal rating scale. | baseline up to 8 years | 
| PRO-CTCAE to evaluate symptomatic toxicities by self-report and the difference between treatment arms | The PRO-CTCAE Measurement System characterizes the frequency, severity, interference, and presence/absence of symptomatic toxicities. The PRO-CTCAE Item Library includes 124 items representing 78 symptomatic toxicities drawn from the CTCAE | baseline up to week 24 | 
| PGIS to evaluate the patient global impression of severity of the Multiple Myeloma and the difference between treatment arms | PGIS is a 1 item questionnaire that evaluates patients' health and assesses if there has been an improvement or decline in clinical status | baseline up to 8 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Maintenance, Teclistamab