A phase II study to assess the safety and efficacy of the dual mTORC1/2 inhibitor vistusertib in relapsed, refractory DLBCL

Hematological Oncology
Toby A EyreGraham P Collins

Abstract

Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are unfit for or relapsed postautologous stem-cell transplantation have poor outcomes. Historically, mTORC1 inhibitors have produced responses in approximately 30% of patients in this setting. mTORC1 inhibitor efficacy may be limited by resistance mechanisms including AKT activation by mTORC2. To date, dual mTORC1/2 inhibitors targeting both the TORC1 and TORC2 complexes have not been investigated in DLBCL. This phase II trial investigated the oral dual mTORC1/2 inhibitor vistusertib in an intermittent dosing schedule of 125 mg b.d. for 2 days per week. Thirty patients received vistusertib and six received vistusertib-rituximab for up to six cycles (28-day cycles). Two partial responses were achieved on monotherapy. Durations of response were 57 and 62 days, respectively, for these patients. 19% had stable disease within six cycles. In the monotherapy arm, the median progression-free survival was1.69 (95% confidence interval [CI] 1.61-2.14) months and median overall survival was 6.58 (95% CI 3.81-not reached) months, respectively. The median duration of response or stable disease across the trial duration was 153 days (95% CI 112-not reached). Tumour...Continue Reading

References

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Citations

Jan 11, 2020·Frontiers in Oncology·Karen Griselda de la Cruz LópezAlejandro García Carrancá
Aug 28, 2020·Expert Opinion on Therapeutic Targets·Pavel Klener
Jan 4, 2021·Journal of Cancer Research and Clinical Oncology·Ting WeiQingshan Li
May 22, 2021·Leukemia·Michael Y He, Robert Kridel
Nov 6, 2021·Scientific Reports·Thanh-Trang VoDavid A Fruman

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