A Study to Assess Adverse Events and Change in Disease Activity of Oral Surzetoclax Alone or in Combination With Subcutaneous and/or Oral Antimyeloma Agents in Adult Participants With Multiple Myeloma (MM)

Official title

A Phase 1/2, Open-Label, Platform Study to Evaluate Safety and Efficacy of the BCL-2 Inhibitor Surzetoclax (ABBV-453) Given as Monotherapy or in Combination With Antimyeloma Regimens in Subjects With Multiple Myeloma

Overview

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 safety and change in disease activity of surzetoclax in adult participants with relapsed/refractory (R/R) MM. Adverse events and change in disease activity will be assessed. Surzetoclax is an investigational drug being developed for the treatment of R/R MM. In Substudy 1 there will be a dose escalation phase where participants will receive various doses of surzetoclax in combination with daratumumab + dexamethasone, to determine the best dose of surzetoclax. This will be followed by a dose expansion and selection phase where participants will receive 1 of 2 doses of surzetoclax in combination with daratumumab + dexamethasone, or daratumumab + dexamethasone + pomalidomide (only during the expansion phase). In Substudy 2, there will be a dose escalation phase where participants will receive various doses of surzetoclax alone. Approximately 130 adult participants with R/R MM will be enrolled in the study in approximately 40 sites worldwide. In Substudy 1 escalation phase, participants will receive oral surzetoclax tablets in combination with subcutaneous (SC) daratumumab injections + oral dexamethasone tablets and in the expansion phase, will receive oral surzetoclax tablets in combination with SC daratumumab injections + oral dexamethasone tablets or daratumumab injections + oral pomalidomide + oral dexamethasone tablets. In Substudy 2, Japanese participants will receive oral surzetoclax tablets. The total study duration is approximately 4.5 years. 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. The effect of the treatment will be frequently checked by medical assessments, blood tests, and side effects.

Interventions

• Drug ABBV-453
  Oral Tablet
• Drug Daratumumab
  Subcutaneous (SC) Injection
• Drug Dexamethasone
  Oral Tablet
• Drug Pomalidomide
  Oral Capsule

Primary outcome measures

• Dose-Limiting Toxicities (DLT)s of ABBV-453 [Time frame: Up to Approximately 45 Months]
• Number of Participants with Adverse Events (AE)s [Time frame: Up to Approximately 4.5 Years]

Secondary outcome measures (7)

• Overall Response Rate (ORR) [Time frame: Up to Approximately 4.5 Years]
• Progression-Free Survival (PFS) [Time frame: Up to Approximately 4.5 Years]
• Duration of Response (DOR) [Time frame: Up to Approximately 4.5 Years]
• Time-to-Progression (TTP) [Time frame: Up to Approximately 4.5 Years]
• Time to Next Treatment [Time frame: Up to Approximately 4.5 Years]
• Minimal Residual Disease (MRD) Negativity [Time frame: Up to Approximately 4.5 Years]
• Overall Survival (OS) [Time frame: Up to Approximately 4.5 Years]

Eligibility criteria

Inclusion criteria

• Documented diagnosis of multiple myeloma (MM) based on standard international myeloma working group (IMWG) diagnostic criteria.
• All participants must have measurable disease per central laboratory with at least 1 of the following assessed within 28 days prior to enrollment:

• Serum M-protein >= 0.5 g/dL (>= 5g/L); OR
• Urine M-protein >= 200 mg/24 hours; OR
• For participants without measurable serum and urine M-protein: Serum free light chain (sFLC) ≥ 10 mg/dL (100 mg/L), provided sFLC ratio is abnormal.
• B-cell lymphoma (BCL)-2 inhibitor treatment naïve.
• t(11;14) positive status and/or BCL2 high status.
• Substudy 1 Dose Escalation Cohorts and Substudy 2:

\-- Must be triple class exposed (PI, IMiD and anti-CD38) and have received 3 to 5 lines of prior antimyeloma therapy, and who have no other appropriate treatment options as deemed by the investigator.

• Substudy 1 Dose Expansion Cohorts:

• Must be double class exposed (PI, IMiD) and have received 1 to 3 lines of prior antimyeloma therapy.

Exclusion criteria

• Major surgery within 4 weeks of study treatment or planned during study participation.
• Active infections: no recent infection requiring systemic treatment that was completed <= 7 days before first dose of study treatment and/or uncontrolled systemic infection.
• Recent infection requiring systemic treatment that was completed <= 7 days before first dose of study treatment and/or uncontrolled active systemic infection.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 11 centers

• University of Southern California /ID# 272414 — Los Angeles
• Yale University School of Medicine /ID# 272447 — New Haven
• Dana-Farber Cancer Institute /ID# 271846 — Boston
• University of Michigan Health System - Ann Arbor /ID# 271536 — Ann Arbor
• Memorial Sloan Kettering Cancer Center - New York - York Avenue /ID# 271214 — New York
• University of North Carolina at Chapel Hill /ID# 272454 — Chapel Hill
• Atrium Health Levine Cancer Institute /ID# 271510 — Charlotte
• Wake Forest Baptist Health /ID# 271294 — Winston-Salem
• … and 3 more centers

France · 5 centers

• CHU de Montpellier - Hopital Saint Eloi /ID# 275570 — Montpellier
• Centre Hospitalier Universitaire de Poitiers /ID# 275563 — Poitiers
• IUCT Oncopole /ID# 275568 — Toulouse
• Centre Hospitalier Universitaire de Nantes, Hotel Dieu -HME /ID# 275562 — Nantes
• Hopital Universitaire Necker Enfants Malades /ID# 275571 — Paris

Israel · 5 centers

• Rabin Medical Center. /ID# 272073 — Petah Tikva
• The Chaim Sheba Medical Center /ID# 271251 — Ramat Gan
• Tel Aviv Sourasky Medical Center /ID# 271252 — Tel Aviv
• Rambam Health Care Campus- Haifa /ID# 271256 — Haifa
• Hadassah Medical Center-Hebrew University /ID# 271253 — Jerusalem

Japan · 5 centers

• Nagoya City University Hospital /ID# 271427 — Nagoya
• University Hospital Kyoto Prefectural University of Medicine /ID# 271911 — Kyoto
• The University of Osaka Hospital /ID# 271636 — Suita-shi
• Japanese Red Cross Medical Center /ID# 272018 — Shibuya-ku
• The Jikei University Hospital /ID# 272091 — Tokyo

Australia · 4 centers

• Liverpool Hospital /ID# 272002 — Liverpool
• Calvary Mater Newcastle /ID# 272498 — Waratah
• St Vincent's Hospital - Melbourne /ID# 271997 — Fitzroy
• Epworth Hospital - Richmond /ID# 272497 — Richmond

Germany · 4 centers

• Universitaetsklinikum Heidelberg /ID# 275598 — Heidelberg
• Klinikum der Universitaet Muenchen Grosshadern /ID# 276658 — Munich
• Universitaetsklinikum Wuerzburg /ID# 276657 — Würzburg
• Universitaetsklinikum Hamburg-Eppendorf /ID# 275803 — Hamburg

Belgium · 3 centers

• UZ Gent /ID# 271432 — Ghent
• Universitair Ziekenhuis Leuven /ID# 272382 — Leuven
• CHU de Liege /ID# 271430 — Liège

Poland · 3 centers

• Uniwersytecki Szpital Kliniczny Nr 1 W Lublinie /ID# 276052 — Lublin
• Uniwersytecki Szpital Kliniczny Nr 4 w Lublinie /ID# 276352 — Lublin
• Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Bada /ID# 2762 — Warsaw

Portugal · 3 centers

• Instituto Portugues de Oncologia de Lisboa Francisco Gentil /ID# 275873 — Lisbon
• Unidade Local de Saude de Braga, EPE /ID# 275853 — Braga
• Instituto Portugues de Oncologia do Porto Francisco Gentil /ID# 275851 — Porto

Sweden · 3 centers

• Karolinska University Hospital Solna /ID# 271674 — Solna
• Sodra Alvsborgs sjukhus /ID# 271822 — Borås
• Sahlgrenska Universitetssjukhuset /ID# 272448 — Gothenburg

Italy · 1 center

• Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico /ID# 276306 — Milan

United Kingdom · 1 center

• The Christie NHS Foundation Trust - Christie Hospital /ID# 276276 — Manchester

Identifiers

NCT: NCT06953960 · M25-275 · 2024-517140-65 · 2024-517140-65-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗