The following article features coverage from the American Society of Clinical Oncology 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

A single-arm, open-label, multi-center phase 2 clinical trial is under way to evaluate temozolomide and olaparib as a treatment combination for patients with advanced uterine leiomyosarcoma (uLMS; Identifier: NCT03880019). The trial details were reported at the ASCO20 Virtual Scientific Program.

“Advanced uLMS is initially treated with chemotherapy,” the trial investigators wrote.  They pointed out that the median progression-free survival (PFS) for doxorubicin or gemcitabine plus docetaxel in this patient population is 4 to 6 months and the median overall survival is 12 to 16 months.

The trial opened to accrual in October 2019 and aims to enroll 22 patients with adavance uLMS. Patients must have an Eastern Cooperative Oncology Group performance status of 2 or lower and have experienced disease progression on 1 or more prior lines of therapy.

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If 5 patients respond, the trial will meet its primary endpoint. An overall response rate (ORR) of 10% will indicate that temozolomide and olaparib is “inactive,” while an ORR of 35% will suggest that the combination may have “superior” activity over temozolomide alone.  Secondary endpoints include PFS and safety.

In addition, tumor biopsies will be collected before treatment to investigate features of “BRCAness.”

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“Emerging evidence suggests that uLMS harbors characteristic HR [homologous recombination] deficiency and features of BRCAness, similar to ovarian, breast, and prostate cancers,” the trial investigators explained.

More specifically, tumors from patients who initially benefit from treatment but later see their disease progress will be used to assess changes in RAD51 foci formation; protein expression of Schlafen family member number 11 (SLFN11), which is a potential biomarker for poly(ADP)-ribose polymerase (PARP) inhibitors; and protein expression of O6-methylguanine-DNA methyl-transferase (MGMT) protein, which can determine whether a person responds to temozolomide.

Also, whether HR deficiency is associated with clinical outcomes will be evaluated.

Read more of Cancer Therapy Advisor‘s coverage of the ASCO 2021 meeting by visiting the conference page.


Ingham M, Allred JB, Gano K, et al. NCI protocol 10250: A phase II study of temozolomide and olaparib for the treatment of advanced uterine leiomyosarcoma. Presented at: ASCO20 Virtual Scientific Program. J Clin Oncol. 2020;38(suppl):abstr TPS11570.