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PMID
Authors M.L. Telli, S. Lord, E. Dean, V. Abramson, H-T. Arkenau, C. Becerra, S.M. Tolaney, R. Tang, M.S. Penney, J. Pollard, G. Conboy, S.Z. Fields, G. Shapiro
Title Initial results of a phase 1 dose expansion cohort of M6620 (formerly VX-970), an ATR inhibitor, in combination with cisplatin in patients with advanced triple-negative breast cancer (NCT02157792)
URL https://www.annalsofoncology.org/article/S0923-7534(20)37666-3/fulltext
Abstract Text Background: ATR is a regulator of the cellular response to replication stress and signals DNA damage repair through homologous recombination. Many cancers depend on ATR to survive DNA damage. VX-970 is a potent, selective inhibitor of ATR with preclinical anticancer activity in combination with DNA-damaging chemotherapy in TNBC models. Given the prevalence of DNA damage repair defects in TNBC, this study evaluated the safety and efficacy of VX-970 in combination with Cis in an expansion cohort of pts with BRCA1/2 wild-type mTNBC. Methods: Eligible pts had advanced ER-, PR-, and HER2- BC with 0-2 prior non–platinum-based therapies. First line pts were eligible if relapse occurred ≥ 3 months after prior (neo)adjuvant chemotherapy. Measurable disease per RECIST 1.1 was required. Of a maximum 50 pts planned for enrollment, ≥30 were required to be BRCA1/2 germline wild-type and to have basaloid molecular subtype tumors on central testing. Pts received intravenous Cis 75 mg/m2 on day 1 with VX-970 140 mg/m2 on days 2 and 9 of each 21-day cycle. In pts intolerant to Cis or at investigator’s discretion, treatment could be switched to carboplatin AUC 5 with VX-970 90 mg/m2. Results: At the time of this analysis, 35 female pts with mTNBC who received ≥1 cycle of study drug were included in the safety set (median age, 48 y [range 35-74 y]). Grade ≥3 related TEAEs occurred in 16/35 pts: neutropenia (n = 8), anemia (n = 5), vomiting (n = 4), nausea (n = 3), and 1 pt each with thrombocytopenia, neutrophil count decreased, platelet count decreased, hypokalemia, generalized weakness, rigors, and acute kidney injury. Of these 35 pts, 18 were BRCA1/2 wild-type and had basaloid TNBC with at least 1 baseline scan and 1 on-treatment scan at the time of the data cut. Preliminary objective response rate was 38.9% (n = 7 [all partial response]), and disease control rate (CR+PR+SD) was 72.2% (n = 13). Conclusions: Combination VX-970 and Cis shows encouraging antitumor activity and tolerability in mTNBC. The study is ongoing; updated safety and efficacy results will be presented. Clinical trial identification: NCT02157792

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References