A Study of SY-1365 in Adult Patients With Advanced Solid Tumours

Official Title

A Phase 1 Study of SY-1365, a Selective CDK7 Inhibitor, in Adult Patients With Advanced Solid Tumours

Summary:

This study consists of two parts. Part 1 is a dose-escalation/safety evaluation to provisionally identify a dose and regimen of SY-1365 for further evaluation in Part 2. Following the identification of a recommended dose and regimen from Part 1, the study entered Part 2 to further evaluate safety and the antitumour activity of SY-1365 in patients with select solid tumours, and to confirm target engagement and downstream pathway impact in patients with any solid tumour histology.

Trial Description

Primary Outcome:

  • (Part 1) First-cycle dose-limiting toxicities (DLTs)
  • (Part 1) ECG QTc Interval
  • (Part 1 and 2) Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Secondary Outcome:
  • Peak Plasma Concentration (Cmax) of SY-1365 as a single agent (Part 1 and 2) and in combination with carboplatin (Part 2 only)
  • Area under the plasma concentration-time curve from time zero to the last quantifiable time point (AUC0-last) of SY-1365 as a single agent (Part 1 and 2) and in combination with carboplatin (Part 2 only)
  • Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC0-INF) of SY-1365 as a single agent (Part 1 and 2) and in combination with carboplatin (Part 2 only)
  • (Part 1 and 2) Terminal elimination half life (t1/2)
  • (Part 1 and 2) Evaluate the PD effects of SY-1365 as a single agent (Part 1 and 2) and in combination with carboplatin or fulvestrant (Part 2 only)
  • (Part 2) Evaluation of Objective Response Rate (ORR) in patients with ovarian cancer, breast cancer, and advanced solid tumours as measured by RECIST v1.1
  • (Part 2) Evaluation of Duration of Response (DoR) in patients with ovarian cancer, breast cancer, and advanced solid tumours as measured by RECIST v1.1
  • (Part 2) Evaluation of Disease Control Rate (DCR) in patients with ovarian cancer, breast cancer, and advanced solid tumours as measured by RECIST v1.1
This study consists of two parts. Part 1 is a dose-escalation/safety evaluation to identify a dose and regimen for further evaluation in Part 2. SY-1365 will be administered intravenously weekly & twice weekly for 3 weeks of each 4 week cycle. Dose escalation will proceed until the determination of the maximum tolerated dose (MTD) or a recommended dose and regimen for evaluation in Part 2 of the study. Part 1 was concluded in September 2018 with a total of 32 evaluable patients. Following the identification of a recommended dose and regimen from Part 1, the study entered Part 2 to further evaluate safety and the antitumour activity of SY-1365 in patients with select solid tumours, and to confirm target engagement and downstream pathway impact in patients with any solid tumour histology. Preliminary anti-tumour activity will be evaluated in up to approximately 102 evaluable patients in Part 2, with SY-1365 administered alone, in combination with carboplatin, or in combination with fulvestrant. Part 2 will consist of five cohorts:
  • Cohort 1: approximately 24 patients with advanced ovarian cancer with 3+ previous lines of treatment. Monotherapy
  • Cohort 2: approximately 24 patients with relapsed ovarian cancer with previous platinum therapy. SY-1365 + Carboplatin
  • Cohort 3: approximately 12 patients with clear cell ovarian cancer. Monotherapy
  • Cohort 4: approximately 20-30 patients with biopsy-accessible, advanced solid tumours of any histology. Monotherapy.
  • Cohort 5: approximately 12 patients with HR+ metastatic breast cancer post CDK4/6 + hormonal therapy treatment. SY-1365 + fulvestrant. Overall, the study may enroll up to approximately 137 evaluable patients across dose escalation (Part 1) and expansion cohorts (Part 2, Cohorts 1, 2, 3, 4, and 5).

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

These resources are provided in partnership with the Canadian Cancer Society