Exploring the Safety and Efficacy of Sonrotoclax (BGB-11417) in Combination with Dexamethasone for Relapsed/Refractory Multiple Myeloma with t(11;14) — Insights into Recommended Phase II Dose 

Dr. Quach reports on the preliminary data from the sonrotoclax plus dexamethasone dose-escalation (DE) cohorts. 

Abstract Title:  

Sonrotoclax (BGB-11417) in Combination with Dexamethasone for the Treatment of Relapsed/Refractory Multiple Myeloma with t(11;14): Safety, Efficacy, and Determination of Recommended Phase 2 Dose Presented at ASH 2023 

What is the purpose of this trial?  

The purpose of the BGB-11417-105 trial (NCT04973605) is to study a new potential treatment, sonrotoclax (BGB-11417), for multiple myeloma. In patients with relapsed or refractory multiple myeloma who have a particular genetic abnormality known as t(11;14) and have not responded well to previous treatments, researchers are investigating the safety and effectiveness of Sonrotoclax. 

The trial aims to understand how sonrotoclax, a drug that targets a protein called BCL2, works in treating multiple myeloma. BCL2 is crucial for the survival of cancer cells, and inhibiting it may be an effective way to combat multiple myeloma. Previous treatments, such as venetoclax, have shown promise, but sonrotoclax is designed to be even more potent in inhibiting BCL2. 

Researchers are exploring different ways to use sonrotoclax in the trial – as a standalone treatment (monotherapy), in combination with dexamethasone (a standard myeloma medication), or combined with dexamethasone and carfilzomib. The goal is to find the right dosage and understand how well Sonrotoclax works in patients with relapsed or refractory multiple myeloma who have the t(11;14) genetic abnormality. 

The trial is currently in phases 1b/2, and the researchers are reporting early data from the dose-escalation cohorts involving sonrotoclax and dexamethasone. The information gathered from this study will provide valuable insights into the potential of sonrotoclax as a treatment option for patients with RRMM. 

In this video: 

Hang Quach, MD, FRACP, FRCPA, MBBS1, (University of Melbourne —Melbourne, Australia) reports on the preliminary data from the sonrotoclax plus dexamethasone dose-escalation (DE) cohorts. 

Conclusion: 

From the abstract: “Sonrotoclax plus dexamethasone was generally well tolerated in patients with relapsed/refractory multiple myeloma harboring t(11;14) at doses up to 640 mg, and initial safety and efficacy results are promising. The Safety Monitoring Committee has recommended 640 mg in combination with dexamethasone as the recommended phase II dose. Recruitment is ongoing for the sonrotoclax in combination with dexamethasone and carfilzomib dose-finding arms and the sonrotoclax plus dexamethasone indication expansion cohort.” 

Trial Information: Abstract #1011  (https://ash.confex.com/ash/2023/webprogram/Paper178735.html)

Doctor Bio: 

Hang Quach, MD, FRACP, FRCPA, MBBS1, is a distinguished hematologist with a focus on clinical and research aspects of hematological malignancies, specializing in multiple myeloma, lymphoma, and myeloid disorders. As a consultant clinical and laboratory hematologist at St. Vincent's Hospital, she also holds the position of Professor of Hematology at the University of Melbourne. Prof Quach is at the forefront of Clinical Hematology and Clinical Hematology Research at St. Vincent's Hospital Melbourne, where her expertise lies in the intricate field of hematological malignancies. 

Her career is marked by a robust commitment to clinical and translational research, with a specific emphasis on advancing novel therapeutics for blood cancers. Prof Quach's objective is not only to broaden treatment options for patients but also to ensure that Australians have access to the most effective treatments. Her translational research is dedicated to understanding myeloma immunology and the cancer-microenvironment. Having secured over $14 million in research funding through competitive grants, industry collaborations, and philanthropy, she has become a prominent figure in myeloma research with numerous publications in the field. 

Prof Quach holds pivotal roles, serving as the co-chair of the myeloma working group at the Australasian Leukaemia Lymphoma Group (ALLG) and deputy-chair of the Myeloma Scientific Advisory Group (MSAG) for Myeloma Australia. In the latter role, she leads the development and biennial update of the Australian National Treatment Guideline for Multiple Myeloma. Passionate about elevating the standard of care for blood cancer patients in Australia, she actively participates in steering committees for various national and international healthcare bodies, demonstrating her commitment to advancing healthcare practices on a broader scale.