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A Phase 1, First-in-Human, Open Label Study Evaluating Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of ABBV-438 in Adult Subjects With Relapsed or Refractory Multiple Myeloma

Basic Information

Recruitment status	Recruiting
Health condition(s) or Problem(s) studied	Multiple myeloma
Date of first enrollment	09/06/2026
Target sample size	127
Countries of recruitment	America,Japan,Israel,Japan
Study type	Interventional
Intervention(s)	Study M25-025 is a Phase 1 FIH, open-label, dose escalation and dose expansion study of ABBV-438 evaluating the safety, tolerability, PK, and preliminary efficacy in subjects with R/R MM. Study M25-025 will be conducted in 2 parts. Part 1 is monotherapy dose escalation and is the FIH evaluation of ABBV-438 administered as a single agent guided by a Bayesian Optimal Interval (BOIN) design. Part 1 aims to identify the maximum tolerated dose (MTD)/maximum administered dose (MAD) and establish recommended Phase 1 expansion doses (RP1EDs) for Part 2. Part 2 will be monotherapy dose expansion. Both parts of the study require subjects to be considered relapsed or refractory to at least 3 or more previous systemic therapies known to provide a clinical benefit for MM, including exposure to a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 therapy. Eligible subjects will receive intravenous ABBV-438 in 28-day cycles until unacceptable toxicity, disease progression, or other protocol-specified reasons for discontinuation are met.

Outcome(s)

Primary Outcome

The safety will be evaluated based upon the assessment of all grade adverse events (AEs), serious AEs (SAEs) reported during the treatment-emergent AE (TEAE) period; clinical laboratory parameters (e.g., hematology, chemistry), vital sign measurements, and electrocardiogram (ECG) results.

Secondary Outcome

The key efficacy endpoint is achievement of partial response (PR), very good partial response (VGPR), complete response (CR) or stringent complete response (sCR) as assessed by investigators per International Myeloma Working Group (IMWG) 2016 criteria Additional efficacy endpoints: - Achievement of VGPR or better - Duration of response (DOR) in subjects who achieved PR, VGPR, CR or sCR - Progression-free survival (PFS) Overall Survival (OS) - Minimal residual disease (MRD) negativity - Pharmacokinetic (PK) parameters, including the area under the serum/plasma concentration-time curve (AUC), maximum observed serum (or plasma, for payload) concentration (Cmax), the time to Cmax (Tmax), and half-life (t1/2), for ABBV-438, will be determined using noncompartmental methods for ABBV-438 conjugate (ADC), total antibody, and unconjugated GRM payload (A-1647462) as applicable. Anti-drug antibodies (ADAs) will be determined, and neutralizing antibodies (nAbs) may be determined, as appropriate. Additional parameters may be calculated and/or analyses may be conducted if appropriate and useful in data interpretation.

Key inclusion & exclusion criteria

Age minimum	>= 18age old
Age maximum	Not applicable
Gender	Both
Include criteria	-Has relapsed or refractory Multiple Myeloma (MM) with documented evidence of progression during or after the participant's last treatment regimen based on the investigator's determination of the standard InternationalMyeloma Working Group (IMWG) (2016) response criteria: - Relapsed defined as previously treated myeloma that progresses and requires initiation of salvage therapy; - Refractory defined as disease that is nonresponsive (failure to achieve minimal response) while on last therapy, or progresses within 60 days of last therapy. - Has measurable disease at screening, defined by at least 1 of the following within 28 days prior to enrollment: - Serum M-protein >= 0.5 g/dL (>=5 g/L); OR; - Urine M-protein >= 200 mg/24 hours; OR; - Involved serum free light chain (sFLC) >= 10 mg/dL (100mg/L), provided serum FLC ratio is abnormal; - Must have had 3 or more prior lines of therapy with exposure to a proteasome inhibitor (PI), an immunomodulatory imide drugs (IMiD), and an anti-CD38 therapy and are intolerant to, or unable to access, available therapies that are known to confer clinical benefit to participants with relapsed or refractory (R/R) MM. Note: A line of therapy consists of relapsed or refractory 1 complete cycle of a single agent, a regimen consisting of a combination of several drugs, or a planned sequential therapy of various regimens.
Exclude criteria	- Known history of Central Nervous System involvement by MM. - History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis.