A Phase 1/2, Open-Label, Platform Study to Evaluate Safety and Efficacy of Etentamig Monotherapy or Etentamig Combinations in Subjects with Multiple Myeloma

The primary objectives of this study are to characterize the safety, toxicity, and tolerability of etentamig administered as monotherapy or in combination with other agents in participants with multiple myeloma, and to determine the recommended doses of etentamig monotherapy or in combination with other agents in this patient population. These objectives are clinically relevant for establishing the therapeutic window and optimal dosing regimens of etentamig, a bispecific antibody targeting BCMA and CD3, in multiple myeloma treatment.

The secondary objectives include:

• To evaluate the preliminary anti-multiple myeloma activity of etentamig monotherapy or in combination with other agents.

• To characterize the pharmacokinetics of etentamig when administered alone or in combination with other agents.

• To evaluate the immunogenicity of etentamig.

This clinical trial enrolled a total of **430 participants** diagnosed with **multiple myeloma**. The study population included both **male** and **female** adults aged 18 years and older. Participants were selected based on a confirmed diagnosis of multiple myeloma according to the International Myeloma Working Group diagnostic criteria, with enrollment encompassing individuals with newly diagnosed, relapsed, or refractory disease depending on the specific substudy. Eligible participants were required to have an **Eastern Cooperative Oncology Group performance status** of 1 or less, indicating relatively preserved functional capacity. Additionally, participants needed to meet specific laboratory value thresholds as defined in the protocol for each substudy during the screening period prior to receiving the first dose of study treatment. The trial population consisted of patients with varying disease stages and treatment histories, reflecting the heterogeneous nature of multiple myeloma presentation and progression.

This is a Phase 1/2, open-label, platform study designed to evaluate the safety and efficacy of **etentamig** administered as monotherapy or in combination with other agents in participants with **multiple myeloma**. The trial employs a platform design that allows for the evaluation of multiple treatment regimens across different substudies. The investigational medicinal product etentamig (ABBV-383) is administered as a **solution for infusion** via the **intravenous** route. Combination therapies include **lenalidomide** (administered orally as capsules), **daratumumab** (administered as solution for injection), **dexamethasone** (administered orally as tablets or via subcutaneous injection), and **carfilzomib** (administered intravenously as solution for infusion).

The primary objectives of the study are to characterize the safety, toxicity, and tolerability of etentamig monotherapy or in combination with other agents in participants with multiple myeloma, and to determine the recommended doses of these treatment regimens. The study includes multiple substudies targeting different patient populations, including transplant-ineligible newly diagnosed multiple myeloma, transplant-eligible newly diagnosed multiple myeloma, and relapsed or refractory multiple myeloma. Each substudy evaluates **dose-limiting toxicity** as a primary endpoint, along with the number of participants experiencing **adverse events**.

Secondary endpoints across all substudies include **complete response rate**, **overall response rate**, **progression-free survival**, **duration of response**, **time-to-progression**, and **minimal residual disease** negativity. These endpoints are assessed according to International Myeloma Working Group criteria. The trial design incorporates both dose-escalation and expansion phases to establish optimal dosing regimens and preliminary efficacy signals.

Principal inclusion criteria require participants to have an **Eastern Cooperative Oncology Group** performance status of 1 or less, confirmed diagnosis of multiple myeloma according to International Myeloma Working Group diagnostic criteria, and laboratory values meeting protocol-specified criteria within the screening period. Participants may have newly diagnosed or relapsed or refractory multiple myeloma depending on the specific substudy requirements.

The estimated recruitment start date is April 30, 2026, with an estimated study completion date of February 28, 2036. The total duration of the study reflects the long-term follow-up required to assess durability of response and survival outcomes in participants with multiple myeloma. Individual participant involvement duration will vary depending on treatment response, disease progression, and tolerability of the study regimen.

Study visits will include a screening visit to assess eligibility criteria and baseline disease characteristics, followed by regular treatment visits for administration of study medications and safety assessments. Follow-up visits will be conducted to monitor disease response through laboratory assessments, imaging studies, and bone marrow evaluations as specified in the protocol. An end-of-study visit will be performed to capture final safety and efficacy data. Participants may be withdrawn from the study early due to disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-specified criteria.

The experimental investigational medicinal product utilized in this clinical trial is Etentamig, also known by the sponsor product code ABBV-383. Etentamig is a human IgG4 monoclonal antibody targeting BCMA and CD3, of biological/biotechnological origin. The active substance is etentamig. The medicinal product is supplied as a solution for infusion and is administered via the intravenous route. Etentamig is evaluated both as monotherapy and in combination with other agents in participants with multiple myeloma. The product will be locally sourced by investigational sites or provided by AbbVie.

Lenalidomide is employed as a non-experimental treatment in this study. Lenalidomide is of chemical origin and is supplied in various pharmaceutical forms including capsule and capsules. The medicinal product is administered via oral use. Lenalidomide serves as part of the combination therapy regimens evaluated in conjunction with etentamig. The product will be locally sourced by investigational sites or provided by AbbVie.

Dexamethasone is utilized as a non-experimental treatment agent in the study. Dexamethasone is of chemical origin and is available in two pharmaceutical forms: tablet for oral use and solution for injection for subcutaneous injection. Dexamethasone is administered via oral use when supplied as tablets and via subcutaneous injection when supplied as solution for injection. This agent is incorporated into combination treatment regimens with etentamig. The product will be locally sourced by investigational sites or provided by AbbVie.

Daratumumab is employed as a non-experimental treatment in this clinical trial. Daratumumab is a medicinal product of biological/biotechnological origin containing the active substance daratumumab, which is a protein. The pharmaceutical form is solution for injection. The route of administration is indicated as solution for injection. Daratumumab is used in combination regimens with etentamig in participants with multiple myeloma. The product will be locally sourced by investigational sites or provided by AbbVie.

Carfilzomib is utilized as a non-experimental treatment agent in the study. Carfilzomib is of chemical origin and is supplied as a solution for infusion. The medicinal product is administered via intravenous use. Carfilzomib is incorporated into combination treatment regimens evaluated with etentamig in participants with multiple myeloma. The product will be locally sourced by investigational sites or provided by AbbVie.

Efficacy will be assessed through multiple endpoints across the substudies of this clinical trial in participants with multiple myeloma. The primary efficacy endpoints include the evaluation of dose-limiting toxicity of etentamig administered as monotherapy or in combination with other agents, including daratumumab and lenalidomide, carfilzomib and dexamethasone, or lenalidomide alone when given as maintenance therapy. Additionally, the number of participants with adverse events will be monitored as a primary endpoint.

Secondary efficacy endpoints will be assessed across all substudies and include complete response rate, overall response rate, progression-free survival, duration of response, time-to-progression, and minimal residual disease negativity. These parameters will be evaluated to characterize the efficacy of etentamig monotherapy or in combination with other agents in participants with newly diagnosed or relapsed or refractory multiple myeloma.