Abstract P1-18-10: A clinical study of samuraciclib (CT7001), a first-in-class, oral, selective inhibitor of CDK7, in patients with advanced triple negative breast cancer (TNBC)

Abstract

Abstract Background: CDK7 inhibition is a promising therapeutic strategy in cancer. CDK7 is a key kinase, regulating cell division, transcription and nuclear receptor function [1]. Although recent advances have been made in the treatment of TNBC this disease is still one of significant unmet need. Materials and Methods: Tolerability and efficacy of Samuraciclib were assessed in a TNBC expansion cohort of the first in human study of Samuraciclib. These patients had metastatic or locally advanced TNBC and had received prior taxane and anthracycline therapy including at least one line of chemotherapy for metastatic or locally advanced disease. Results: From 29th January 2019 to 12th April 2021, 23 women with advanced TNBC were recruited and dosed with Samuraciclib 360mg OD. Treatment has generally been well tolerated with all patients remaining on treatment until disease progression. The most common adverse drug reactions (AE) were: G1-2 Nausea (96%), Vomiting (52%) and Diarrhea (91%). There were 4 dose reductions to manage upper GI adverse events of nausea and/or vomiting. G3 events were as follows: 2 Grade 3 Diarrhea, 1 Grade 3 Vomiting, 1 Grade 3 Fatigue, 1 Grade 3 Stomatitis, 1 Grade 3 Anaemia and 1 Grade 4 Thrombocytopenia21 patients have had follow-up evaluations for assessment of efficacy. Stable disease was achieved in 14 patients, 1 with partial response (being on treatment for 72 weeks) and 7 patients with progressive disease; two additional patients remain on compassionate use treatment, following disease progression by RECIST. 5 patients have been on treatment for at least 24 weeks of whom 3 have exceeded 1 year. Conclusions: Samuraciclib demonstrated an acceptable safety and tolerability profile with evidence of antitumour activity in advanced TNBC.