Study of Intravenously (IV) Infused Etentamig in Combination With an Oral Cereblon E3 Ligase Modulatory Drug (CELMoD) Agent Assessing Adverse Events and Change in Disease Activity in Adult Participants With Relapsed or Refractory Multiple Myeloma

Phase 1

Not yet recruiting

• Conditions: Multiple Myeloma
• Interventions: Drug: Etentamig; Drug: Iberdomide

• Registration Number: NCT06896916
• Lead Sponsor: TeneoOne Inc.

Brief Summary

Multiple myeloma (MM) is a plasma cell disease characterized by the growth of clonal plasma cells in the bone marrow. The purpose of this study is to assess the adverse events and change in disease activity of etentamig in combination with a cereblon E3 ligase modulatory drug (CELMoD) agent in adult participants with relapsed/refractory (R/R) multiple myeloma (MM). Adverse events and change in disease state will be assessed.

Etentamig is an investigational drug being developed for the treatment of R/R MM. Study doctors put the participants in groups called treatment arms. Multiple doses of etentamig in combination with iberdomide will be explored. Each treatment arm receives a different dose of etentamig and iberdomide to determine a tolerable dose. Approximately 135 adult participants with R/R MM will be enrolled in the study in approximately 50 sites worldwide.

In phase 1 participants will receive escalating intravenous (IV) etentamig in combination with oral iberdomide. In phase 2 participants will receive IV etentamig at one of two doses in combination with oral iberdomide, as part of the approximately 129 month study duration.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and and monitoring of side effects.

Detailed Description

B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) or BCMA antibody-drug conjugate (ADC) are allowed.

Study Timeline

• Status Verified: 2025-03
• Study First Submitted: 2025-03-19
• Study First Submitted QC: 2025-03-19
• Last Update Submitted: 2025-03-19
• Study First Posted: 2025-03-26
• Last Update Posted: 2025-03-26
• Study Start: 2025-06-30
• Primary Completion: 2036-03
• Study Completion: 2036-03

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 135

Inclusion Criteria

• Eastern Cooperative Oncology Group (ECOG) performance of 0 to 1.
• Must have confirmed diagnosis of Relapsed/Refractory Multiple Myeloma (RRMM) after the participant's last treatment, as outlined in the protocol.
• All participants must have measurable diseases per central laboratory as outlined in protocol

Exclusion Criteria

• Has received prior etentamig treatment.
• Prior exposure to BCMA-targeted therapy as noted in the protocol.
• Has received prior cereblon E3 ligase modulatory drug (CELMoD) (iberdomide or mezigdomide).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 1: ABBV-383 Dose Escalation	Etentamig	In phase 1 participants will receive escalating Etentamig in combination with iberdomide, as part of the approximately 129 month study duration.
Phase 1: ABBV-383 Dose Escalation	Iberdomide	In phase 1 participants will receive escalating Etentamig in combination with iberdomide, as part of the approximately 129 month study duration.
Phase 2: ABBV-383 Dose Expansion Dose A	Etentamig	In phase 2 participants will receive Etentamig at dose A in combination with iberdomide, as part of the approximately 129 month study duration.
Phase 2: ABBV-383 Dose Expansion Dose A	Iberdomide	In phase 2 participants will receive Etentamig at dose A in combination with iberdomide, as part of the approximately 129 month study duration.
Phase 2: ABBV-383 Dose Expansion Dose B	Etentamig	In phase 2 participants will receive Etentamig at dose B in combination with iberdomide, as part of the approximately 129 month study duration.
Phase 2: ABBV-383 Dose Expansion Dose B	Iberdomide	In phase 2 participants will receive Etentamig at dose B in combination with iberdomide, as part of the approximately 129 month study duration.

Primary Outcome Measures

Name	Time	Method
Phase 1: Dose-Limiting Toxicities (DLT)s of Etentamig when given in Combination with Iberdomide in Participants with Relapsed/Refractory Multiple Myeloma (RRMM)	Up to Approximately 56 Days	DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications.
Number of Participants with Adverse Events (AE)s	Up to Approximately 129 Months	An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.

Secondary Outcome Measures

Name	Time	Method
Partial Response (PR) Response Rate (RR)	Up to 3 Years	PR is defined \>= 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by \>= 90% or to \< 200 mg per 24 hours, if the serum and urine M-protein are unmeasurable, a \>= 50% decrease in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria, if the serum and urine M-protein are unmeasurable, and serum free light assay is also unmeasurable, a \>= 50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma cell percentage was \>= 30%, \>= 50% reduction in the size of soft tissue plasmacytomas is also required, if present at baseline.
Very Good Partial Response (VGPR) RR	Up to 3 Years	VGPR is defined as serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>= 90% reduction in serum M-protein plus urine M-protein \< 100 mg per 24 hours, for participants in whom the only measurable disease is by serum free light chains (FLC) levels, VGPR is defined as \>= 90% decrease in the difference between involved and uninvolved FLC levels.
Complete Response (CR) RR	Up to 3 Years	CR is defined negative immunofixation on the serum and urine (regardless of whether disease at baseline was measurable on serum, urine, both, or neither), disappearance of any soft tissue plasmacytomas, \< 5% plasma cells in bone marrow, and for participants in whom the only measurable disease is by serum FLC levels, a normal FLC ratio is also required.
Stringent Complete Response (sCR) RR	Up to 3 Years	sCR is defined negative immunofixation on the serum and urine (regardless of whether disease at baseline was measurable on serum, urine, both, or neither), disappearance of any soft tissue plasmacytomas, \< 5% plasma cells in bone marrow, normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry (kappa/lambda ratio \<= 4:1 or \>= 1:2 for kappa and lambda participants, respectively, after counting \>= 100 plasma cells).
Overall Response Rate (ORR)	Up to 3 Years	ORR (PR + VGPR + CR + sCR) will be defined as the proportion of participants who achieved a PR or better.
Progression-Free Survival (PFS)	Up to 3 Years	PFS is defined as the number of days from the date of first dose to the date of earliest disease progression or death.
Duration of Response (DOR)	Up to 3 Years	DOR is defined as the number of days from the date of first response (sCR, CR, VGPR, or PR) to the earliest recurrence, progressive disease, or death, whatever occurs first.
Time-to-Progression (TTP)	Up to 3 Years	TTP will be defined as the number of days from the date of first dose to the date of earliest disease progression.
Minimal Residual Disease (MRD) negativity	Up to 3 Years	The MRD negativity rate is defined as the proportion of participants who achieve MRD negative status.