M21-406
Research type
Research Study
Full title
First-in-Human Study of the BCL-2 Inhibitor ABBV-453 in Biomarker-Selected Subjects with\nRelapsed or Refractory Multiple Myeloma
IRAS ID
1007223
Contact name
Aleksandra Jankielewicz
Contact email
Sponsor organisation
AbbVie Deutschland GmbH & Co. KG
Eudract number
2022-501685-22
Clinicaltrials.gov Identifier
Research summary
This is a two-part, first-in-human (FIH), proof of concept, open-label (it means that both participant and investigator will know what medication is administered) study to evaluate the safety, pharmacokinetics (PK), and initial efficacy of ABBV-453 in biomarker-selected participants with Relapsed or Refractory Multiple Myeloma (R/R MM).ABBV-453 is a novel and highly potent and selective small molecule inhibitor of b-cell lymphoma-2 (BCL-2), a member of the BCL-2 family of anti-apoptotic proteins. ABBV-453 disrupts the endogenous interactions between BCL-2 and pro-apoptotic BCL-2 family members to drive rapid and potent caspase-dependent apoptosis (the death of cells) of human tumour cells that depend upon BCL-2 for survival. This may translate to clinical efficacy in patients with certain hematologic malignancies. Part 1 (dose escalation part) will investigate ABBV-453 as a single agent, beginning at 160 mg, and following a 2-step dose escalation strategy up to 240 mg and 320 mg to identify the maximum tolerated dose (MTD) / maximum administered dose (MAD) and inform on the doses for comparison in combination with dexamethasone. Dexamethasone provides relief for inflamed areas of the body. Dexamethasone is a corticosteroid (cortisone-like medicine or steroid). It works on the immune system to help relieve swelling, redness, itching, and allergic reactions.\nDose escalation will be guided by a Bayesian optimal interval (BOIN) design based on the cumulative number of participants who experience a dose limiting toxicity (DLT) at a given ABBV-453 dose level.\nPart 2 of this study (dose expansion part) will investigate multiple doses of ABBV-453 in combination with fixed doses of dexamethasone.\n\nPart 1 of the study plans to enrol approximately 15-21 participants, and Part 2 of the study plans to enrol approximately 53 participants. All participants are required to be refractory to or intolerant of all established therapies known to provide clinical benefit in MM.
REC name
London - Brent Research Ethics Committee
REC reference
23/LO/0308
Date of REC Opinion
27 Jul 2023
REC opinion
Further Information Favourable Opinion