A Study to Compare Linvoseltamab Monotherapy and Linvoseltamab + Carfilzomib Combination Therapy With Standard-of-Care Combination Regimens in Adult Participants With Relapsed/Refractory Multiple Myeloma (RRMM)

Keywords

• BCMA X CD3 Bispecific Monoclonal Antibody
• Bispecific combination therapy
• Linvoseltamab
• Carfilzomib
• Proteasome inhibitor

Eligibility criteria

Study arms

• Experimental
  Part 1: Arm A

  Drug: Linvoseltamab

• Experimental
  Part 1: Arm B

  Drug: Linvoseltamab · Drug: Carfilzomib

• Experimental
  Part 2: Arm A

  Drug: Linvoseltamab

• Experimental
  Part 2: Arm B

  Drug: Linvoseltamab · Drug: Carfilzomib

• Experimental
  Part 2: Arm C

  Drug: Carfilzomib · Drug: Daratumumab · Drug: Dexamethasone · Drug: Pomalidomide · Drug: Bortezomib

Interventions

• DrugLinvoseltamab

  Administered per the protocol

  Also known as: REGN5458, Lynozyfic™

• DrugCarfilzomib

  Administered per the protocol

  Also known as: Kyprolis®

• DrugDaratumumab

  Administered per the protocol

  Also known as: Darzalex Faspro®, Darzalex®

• DrugDexamethasone

  Administered per the protocol

  Also known as: Dexahexal®

• DrugPomalidomide

  Administered per the protocol

  Also known as: Imnovid®, Pomalyst®

• DrugBortezomib

  Administered per the protocol

  Also known as: Velcade®

Primary outcomes

1. Occurrence of Treatment Emergent Adverse Events (TEAEs)

   Part 1

   Time frame: Up to 5 years

2. Severity of TEAEs

   Part 1

   Time frame: Up to 5 years

3. Occurrence of Adverse Events of Special Interest (AESI)

   Part 1

   Time frame: Up to 5 years

4. Severity of AESIs

   Part 1

   Time frame: Up to 5 years

5. Occurrence of Serious Adverse Events (SAEs)

   Part 1

   Time frame: Up to 5 years

6. Severity of SAEs

   Part 1

   Time frame: Up to 5 years

7. Minimal Residual Disease (MRD)-negative Complete Response (CR)

   Part 2

   Time frame: At 12 months

8. Progression-Free Survival (PFS) per IMWG response criteria as determined by BIRC

   Part 2

   Time frame: Up to 5 years

Secondary outcomes

1. Occurrence of grade ≥2 Cytokine Release Syndrome (CRS)

   Part 1

   Time frame: Up to 28 days

2. Timing of grade ≥2 CRS

   Part 1

   Time frame: Up to 28 days

3. Overall Survival (OS)

   Part 2

   Time frame: Up to 7 years

4. Achievement of Partial Response (PR) or better per IMWG response criteria as determined by BIRC

   Part 2

   Time frame: Up to 5 years

5. Achievement of Very Good Partial Response (VGPR) or better per IMWG response criteria as determined by BIRC

   Part 2

   Time frame: Up to 5 years

6. Achievement of CR or better per IMWG response criteria as determined by BIRC

   Part 2

   Time frame: Up to 5 years

7. Duration Of Response (DOR) as per IMWG response criteria

   Part 2

   Time frame: Up to 5 years

8. Time To Progression (TTP) as per IMWG response criteria

   Part 2

   Time frame: Up to 5 years

9. Time To Next Treatment (TTNT)

   Part 2

   Time frame: Up to 5 years

10. Second PFS

    Part 2

    Time frame: Up to 5 years

11. MRD-negative CR criteria at any time

    Part 2

    Time frame: Up to 5 years

12. Time to PR IMWG response category

    Part 2

    Time frame: Up to 5 years

13. Time to VGPR IMWG response category

    Part 2

    Time frame: Up to 5 years

14. Time to CR IMWG response category

    Part 2

    Time frame: Up to 5 years

15. Time to stringent Complete Response (sCR) IMWG response category

    Part 2

    Time frame: Up to 5 years

16. Sustained MRD-negative CR

    Part 2

    Time frame: Up to 5 years

17. Duration of MRD-negative CR

    Part 2

    Time frame: Up to 5 years

18. Occurrence of TEAEs

    Part 2

    Time frame: Up to 5 years

19. Severity of TEAEs

    Part 2

    Time frame: Up to 5 years

20. Occurrence of AESIs

    Part 2

    Time frame: Up to 5 years

21. Severity of AESIs

    Part 2

    Time frame: Up to 5 years

22. Occurrence of SAEs

    Part 2

    Time frame: Up to 5 years

23. Severity of SAEs

    Part 2

    Time frame: Up to 5 years

24. Concentrations of linvoseltamab in serum over time

    Part 2

    Time frame: Up to 5 years

25. Incidence of Antidrug Antibodies (ADAs) to linvoseltamab

    Part 2

    Time frame: Up to 5 years

26. Magnitude of ADAs to linvoseltamab

    Part 2

    Time frame: Up to 5 years

27. Concentrations total soluble B-cell Maturation Antigen (sBCMA) in serum over time

    Part 2

    Time frame: Up to 5 years

28. Change from baseline in Global Health Status (GHS)/Quality of Life (QoL), per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)

    Part 2 The EORTC QLQ-C30 is a 30-item validated questionnaire developed to measure patient-reported QoL using 1 GHS/QoL scale, 5 functioning scales (physical, role, emotional, cognitive and social) and 9 symptom scales / items (fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) among patients with cancer. Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much."

    Time frame: Up to 5 years

29. Change from baseline in Physical Functioning (PF), per EORTC QLQ-C30

    Part 2

    Time frame: Up to 5 years

30. Change from baseline in Role Functioning (RF), per EORTC QLQ-C30

    Part 2

    Time frame: Up to 5 years

31. Change from baseline in pain, per EORTC QLQ-C30

    Part 2

    Time frame: Up to 5 years

32. Change from baseline in fatigue, per EORTC QLQ-C30

    Part 2

    Time frame: Up to 5 years

33. Change in patient reported Disease Symptoms (DS) per EORTC Quality of Life Questionnaire-Multiple Myeloma (MM) module 20 [QLQ-MY20])

    Part 2 EORTC QLQ-MY20 is an accompanying 20-item validated questionnaire that measure quality of life among patients living with MM across 4 scales (disease symptoms, side effect of treatment, body image and future perspective). A high score represents a high level of symptoms or problems.

    Time frame: Up to 5 years

34. Change in patient reported Treatment Side Effects (TSE) per EORTC QLQ-MY20

    Part 2

    Time frame: Up to 5 years

35. Change in patient-reported health state per EuroQoL-5 Dimension-5 Level Scale [EQ-5D-5L]) Visual Analogue Scale (VAS)

    Part 2 The EQ-5D-5L is a generic questionnaire that measures HRQoL across 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) across 5 levels (no problems, slight problems, some problems, severe problems and extreme problems) and a VAS of pain (where 0: no pain and 10: worst pain), higher scores indicate higher pain.

    Time frame: Up to 5 years

36. Change in patient-reported overall impact of treatment per Functional Assessment of Chronic Illness Therapy (FACIT) item GP5

    Part 2 FACIT Item GP5 is a recommended item by the Federal Drug Administration (FDA) in its recent draft guidance for cancer trials to assess patient-reported overall impact of treatment toxicity. It uses a single item "I am bothered by side effects of treatment" on a 5-point scale (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much)

    Time frame: Up to 5 years

Individual participant data

Plan to share: Yes — All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.

Supporting information: Study protocol, Sap, Icf, Csr, Analytic code