Clinical trial · Interventional
First in Human Dose Escalation of M3258 as a Single Agent and Expansion Study of M3258 in Combination With Dexamethasone
A Phase I Open Label First in Human Dose Escalation of the Immunoproteasome Inhibitor M3258 as a Single Agent and Expansion Study of M3258 in Combination With Dexamethasone in Participants With Relapsed Refractory Multiple Myeloma
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Why stopped (as posted): The study was early discontinued due to lack of participant enrollment.
Summary
Brief summary (as posted)
The purpose of this study was to determine the safety, tolerability, pharmacokinetics, pharmacodynamics and early efficacy signs of M3258 as a single agent and co-administered with dexamethasone in participants with Relapsed Refractory Multiple Myeloma (RRMM).
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Multiple Myeloma | Multiple Myeloma | CURATED_EXACT | 0.92 |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| M3258 | Drug | — | UNRESOLVED |
| M3258 20 mg | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (3)
- type
- EXPERIMENTAL
- label
- M3258 10 mg QD
- interventionNames
- Drug: M3258
- type
- EXPERIMENTAL
- label
- M3258 10 mg Twice per Week
- interventionNames
- Drug: M3258
- type
- EXPERIMENTAL
- label
- M3258 20 mg Twice per Week
- interventionNames
- Drug: M3258 20 mg
Primary outcomes (6)
- measure
- Part A: Number of Participants With Dose-Limiting Toxicities (DLTs) as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * Participants having Eastern Co-operative Oncology Group (ECOG) Performance Status less than or equals to (\<=) 1 * Adequate hematological, hepatic and renal function as defined in the protocol * Participant must have measurable disease of Multiple Myeloma (MM) and received greater than (\>) 3 prior lines of therapy for MM including a Proteasome Inhibitors (PI), an Immunomodulatory Imide Drug (IMiD) and an anti-CD38 mAb or who are refractory to at least PI agent (carfilzomib or bortezomib) and IMiD according to the International Myeloma Working Group (IMWG) criteria * Participant must have documented evidence progressive disease as defined by the IMWG criteria either on or after their last regimen * Other protocol defined inclusion criteria could apply Exclusion Criteria: * Any condition, including any uncontrolled disease state that in the Investigator's opinion constitutes an inappropriate risk or a contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation. * An active second malignancy or evidence of disease of cancer (other than MM) before the date of enrollment (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the Investigator, with concurrence with the Sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years). * Cerebrovascular accident/stroke (\< 6 months prior enrollment) or neurologic instability per clinical evaluation due to tumor involvement of the Central Nervous System * Diagnosis of fever within 1 week prior to study intervention administration * Part B: Participants planning to undergo a stem cell transplant should not be enrolled to reduce disease burden prior to transplant. * Other protocol defined exclusion criteria could apply
References
Publications (2)
- RESULTSanderson MP, Friese-Hamim M, Walter-Bausch G, Busch M, Gaus S, Musil D, Rohdich F, Zanelli U, Downey-Kopyscinski SL, Mitsiades CS, Schadt O, Klein M, Esdar C. M3258 Is a Selective Inhibitor of the Immunoproteasome Subunit LMP7 (beta5i) Delivering Efficacy in Multiple Myeloma Models. Mol Cancer Ther. 2021 Aug;20(8):1378-1387. doi: 10.1158/1535-7163.MCT-21-0005. Epub 2021 May 27. PMID 34045234
- DERIVEDLignet F, Esdar C, Walter-Bausch G, Friese-Hamim M, Stinchi S, Drouin E, El Bawab S, Becker AD, Gimmi C, Sanderson MP, Rohdich F. Translational PK/PD Modeling of Tumor Growth Inhibition and Target Inhibition to Support Dose Range Selection of the LMP7 Inhibitor M3258 in Relapsed/Refractory Multiple Myeloma. J Pharmacol Exp Ther. 2023 Jan;384(1):163-172. doi: 10.1124/jpet.122.001355. Epub 2022 Oct 23. PMID 36273822