Wednesday, November 27, 2019 IND 229 Publication: A Phase Ib Trial of Durvalumab in Combination with Trastuzumab in HER2 - Positive Metastatic Breast Cancer Chia S, Bedard PL, Hilton J, Amir E, Gelmon K, Goodwin R, Villa D, Cabanero M, Tu D, Tsao M, Seymour L. A Phase Ib Trial of Durvalumab in Combination with Trastuzumab in HER2 - Positive Metastatic Breast Cancer (CCTG IND.229) (ONLINE). The Oncologist 24: 2019. http://theoncologist.alphamedpress.org/content/early/2019/08/16/theoncologist.2019-0321.abstract The purpose of this study was to find the highest dose of durvalumab that can be tolerated without causing very severe side effects when receiving standard treatment and to see what effects the study drug has on this type of cancer. The researchers doing this study are also interested in looking for markers that will help predict which patients are most likely to be helped by durvalumab when receiving standard treatment and what effects durvalumab has on this type of cancer. Results: Fifteen patients were accrued from April to December 2016, of which 14 were evaluable for response. Median age was 54 years (range 40–86); the majority had visceral disease (87%) and at least three prior (adjuvant and/or metastatic) lines of chemotherapy (73%), including trastuzumab (93%), pertuzumab (60%), and trastuzumab‐emtansine (93%) for MBC. No dose‐limiting toxicities were observed at dose level 1 (n = 6) or dose expansion (n = 9) during cycle 1. One patient developed a grade ≥3 immune‐related adverse event (grade 4 diabetes mellitus). No responses by RECIST were seen, with 4 of 14 patients (29%) demonstrating stable disease as best response at week 6 (median duration, 2.7 months). All patients had <1% PD‐L1 expression on either archival tissue (7/15) or prestudy biopsy (8/15). In the dose expansion cohort, evaluable pretreatment and on‐treatment tumor biopsies (n = 5) showed minimal CD8 cell infiltration. Conclusion: The RP2D of durvalumab and trastuzumab is standard full doses of both agents. No significant clinical activity was observed in patients with heavily pretreated HER2‐positive PD‐L1‐negative MBC. IND 222 Publication: A phase I study of vistusertib (dual mTORC1/2 inhibitor) in patients with previously treated glioblastoma multiforme Lapointe S, Mason W, MacNeil M, Harlos C, Tsang R, Sederias J, Luchman HA, Weiss S, Rossiter JP, Tu D, Seymour L, Smoragiewicz M. A phase I study of vistusertib (dual mTORC1/2 inhibitor) in patients with previously treated glioblastoma multiforme: a CCTG study (ONLINE). Invest New Drugs 2019. https://link.springer.com/article/10.1007/s10637-019-00875-4?wt_mc=Internal.Event.1.SEM.ArticleAuthorOnlineFirst&utm_source=ArticleAuthorOnlineFirst&utm_medium=email&utm_content=AA_en_06082018&ArticleAuthorOnlineFirst_20191111 The standard or usual treatment for this disease is standard chemotherapy alone. AZD2014 is a new type of drug for glioblastoma multiforme. In the laboratory it has been shown to slow the growth of glioblastoma multiforme. In some animal studies AZD2014 seemed to work better when given with a drug called temozolomide. Conclusion: This phase I study of the dual mTORC1/2 inhibitor vistusertib in combination with TMZ in patients with GBM at first recurrence demonstrated a favorable safety profile at the tested dose levels. Although only one partial response was noted, prolonged disease stability was seen in 38% of patients. Despite the decision to abandon the development of vistusertib, further strategies utilizing dual mTORC1/2 inhibitors in selected patients with GBM may merit additional evaluation.
