Syros Pharmaceuticals, Inc. announced that the first patient has been dosed in the Phase 1 clinical trial of SY-5609, its highly selective and potent oral cyclin-dependent kinase 7 (CDK7) inhibitor. The trial is enrolling patients with advanced breast, colorectal, lung or ovarian cancer, or with solid tumors of any histology that harbor Rb pathway alterations. SY-5609 has shown substantial anti-tumor activity, including complete regressions, in multiple preclinical models of solid tumors, including breast, colorectal, lung and ovarian cancers, at doses below the maximum tolerated dose (MTD). In preclinical studies of breast, lung and ovarian cancers, deeper and more sustained responses were associated with the presence of Rb pathway alterations. SY-5609 has also shown anti-tumor activity in combination with fulvestrant in treatment-resistant models of estrogen receptor-positive breast cancer, including those resistant to both fulvestrant and a CDK4/6 inhibitor. The Phase 1 trial is a multi-center, open-label, dose-escalation trial that is expected to enroll approximately 60 patients with advanced breast, colorectal, lung or ovarian cancer, or with solid tumors of any histology that harbor Rb pathway alterations. The primary objectives of the dose escalation are to assess the safety and tolerability of escalating doses of SY-5609, with the goal of establishing an MTD. Additional objectives include assessments of anti-tumor activity, pharmacokinetics (PK), pharmacodynamics (PD) and potential predictive biomarkers, including Rb pathway alterations. In a future expansion portion of the Phase 1 trial, multiple cohorts are planned to further evaluate the safety and anti-tumor activity of SY-5609 as both a single agent and in combination with other therapies. Syros expects to report initial safety, tolerability and PK/PD data in the fourth quarter of 2020 and additional dose-escalation data, including clinical activity, in mid-2021.