Mazyar Shadman, MD, MPH, on Chronic Lymphocytic Leukemia: Recruiting for the CELESTIAL-TNCLL Study
2024 ASCO Annual Meeting
Mazyar Shadman, MD, MPH, of Fred Hutchinson Cancer Center, discusses an ongoing phase III study of the BCL2 inhibitor sonrotoclax plus zanubrutinib vs venetoclax and obinutuzumab for patients with treatment-naive chronic lymphocytic leukemia. The investigators are recruiting internationally (see NCT06073821; Abstract TPS7087).
Transcript
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
This year at the ASCO meeting, I had the opportunity of presenting a trial in progress. This is CELESTRIAL-CLLTN trial, which is a global head-to-head Phase III trial comparing the investigational combination using zanubrutinib, a second generation BTK inhibitor, in combination with sonrotoclax, which is a novel BCL2 inhibitor, and we are comparing that to a standard arm of venetoclax plus obinutuzumab for treatment of first line CLL patients who require treatment.
As a background, we currently have two options for first line treatment of CLL. We either go with continuous BTK inhibitor therapy until progression or intolerance, or we use a time-limited approach using venetoclax in combination with obinutuzumab. If the study is positive, we'll introduce another time-limited option, which is all oral and chemoimmunotherapy free. Zanubrutinib is already approved for CLL in all lines of therapy, and in clinical trial has been shown to be superior to ibrutinib both from the efficacy and safety standpoint.
Sonrotoclax is a novel BCL2 inhibitor, has shown very promising activity both from the safety and efficacy standpoints. In fact, in a study that was presented at ASH in 2023, we saw an extremely effective combination and also very well-tolerated treatment option for CLL patients.
What this study is trying to do is comparing sonrotoclax and zanubrutinib to venetoclax and obinutuzumab. This is a global study with more than 640 patients planned to be enrolled, and patients will be randomized to receive one of the two options. The primary endpoint is progression-free survival, and we are going for superiority of the investigational arm over the standard of care arm.
This study is currently ongoing, and we encourage our colleagues to contact the participating sites and PIs if they have any patients who requires treatment for first line CLL.
The ASCO Post Staff
Alicia Morgans, MD, MPH, of Dana-Farber Cancer Institute, and Susan Halabi, PhD, of the Duke Cancer Institute and Duke University School of Medicine, discuss a clinical-genetic model that identified novel circulating tumor DNA alterations that are prognostic of overall survival and may help to classify patients with metastatic castration-resistant prostate cancer into risk groups useful for selecting trial participants (Abstract 5007).
The ASCO Post Staff
Brian I. Rini, MD, of Vanderbilt Ingram Cancer Center, discusses phase III findings of the KEYNOTE-426 study of pembrolizumab plus axitinib vs sunitinib for patients with advanced renal cell carcinoma. He details the exploratory biomarker results, including RNA sequencing, whole-exome sequencing, and PD-L1 (Abstract 4505).
The ASCO Post Staff
Anthony M. Joshua, MBBS, PhD, of Princess Margaret Cancer Centre, discusses results from the MAST study, which explored the question of whether metformin could reduce disease progression in men with low-risk prostate cancer who are undergoing active surveillance (LBA5002).
The ASCO Post Staff
Peter Riedell, MD, of The University of Chicago, discusses phase III findings on the regimen of brentuximab vedotin in combination with lenalidomide and rituximab for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). This therapy demonstrated a survival advantage in the third-line setting, but as this is an interim analysis, questions remain regarding long-term safety and duration of response, according to Dr. Riedell (Abstract LBA7005).
The ASCO Post Staff
Katherine C. Fuh, MD, PhD, of the University of California, San Francisco, discusses phase III findings of the AXLerate-OC trial, showing that batiraxcept with paclitaxel compared to paclitaxel alone improved progression-free and overall survival in patients with platinum-resistant recurrent ovarian cancer whose tumors were AXL-high in an exploratory analysis (LBA5515).