A Phase 1 Study of SY-1365 in Adult Patients With Advanced Solid Tumors

Description

This study will consist 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. Approximately 35 patients with advanced solid tumors will be enrolled into Part 1 of the study. Following the identification of a recommended dose and regimen from Part 1, the study will enter Part 2 to further evaluate safety and the antitumor activity of SY-1365 in patients with select solid tumors, and to confirm target engagement and downstream pathway impact in patients with any solid tumor histology. Part 2 will consist of two cohorts: - Cohort 1: approximately 25 patients with small cell lung cancer (SCLC), triple negative breast cancer (TNBC), or ovarian cancer (OC) - Cohort 2: approximately 10 patients with biopsy-accessible, advanced solid tumors of any histology

Study Start Date

May, 12 2017

Estimated Completion Date

November 2019

Interventions

  • Drug: SY-1365

Study ID

Syros Pharmaceuticals -- SY-1365-101

Status

Recruiting

Trial ID

NCT03134638

Study Type

Interventional

Trial Phase

Phase 1

Enrollment Quota

70

Sponsor

Syros Pharmaceuticals

Inclusion Criteria

  • 18 years of age or older
  • Disease status
  • Part 1: any histologically-confirmed metastatic or unresectable solid tumor for which standard curative or palliative measures do not exist or are no longer effective
  • Part 2, Cohort 1: histologically-confirmed diagnosis of SCLC, TNBC, or ovarian cancer (high-grade serous type) for which standard curative or palliative measures do not exist or are no longer effective
  • Part 2, Cohort 2: any histologically-confirmed metastatic or unresectable solid tumor for which standard curative or palliative measures do not exist or are no longer effective
  • At least 1 measurable lesion by RECIST 1.1
  • Prior treatment (Part 2, Cohort 1 only)
  • SCLC: must have received prior platinum doublet therapy
  • TNBC: must have received prior taxane therapy
  • Ovarian Cancer (high-grade serous type): must have received prior platinum doublet therapy, and in the opinion of the Investigator is unlikely to benefit from additional lines of platinum-based therapy
  • Part 2 Cohort 2 only
  • Must have accessible tumor tissue and be willing to undergo tumor tissue sampling (biopsies/aspirates) pre
  • and post-treatment
  • All toxicities (except alopecia) from prior cancer treatments must have resolved to ? Grade 1 or returned to baseline levels prior to enrollment
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Life expectancy > 3 months
  • absolute neutrophil count: ? 1.5 x 109/L
  • platelets: ? 100 x 109/L
  • hemoglobin: ? 9 g/dL
  • total bilirubin ? 1.5 institutional upper limit of normal [ULN])
  • AST (SGOT)/ ALT (SGPT): ? 3.0 x institutional ULN
  • Creatinine ? 1.5 x institutional ULN OR creatinine clearance ? 60 mL/min by Crockoft-Gault for participants with creatinine levels above institutional normal
  • Negative pregnancy test for women of child bearing potential

Exclusion Criteria

  • Chemotherapy or limited field radiotherapy within 2 weeks, wide field radiotherapy within 4 weeks, or nitrosoureas or mitomycin C within 6 weeks prior to entering the study
  • Major surgery within 2 weeks of starting the study treatment, or not recovered to baseline status from the effects of surgery received > 2 weeks prior
  • Received any other investigational agents within 4 weeks prior to enrollment, or < 5 half-lives since completion of previous investigational therapy, whichever is shorter
  • Received previous non-cytotoxic, FDA-approved anticancer agent within previous 2 weeks, or < 5 half-lives since completion of previous therapy, whichever is shorter
  • Prior exposure to transcriptional kinase family CDK inhibitors, such as the CDK7 and CDK9 inhibitors alvocidib (Flavopiridol), dinaciclib, and seliciclib. Exception: previous exposure to cell cycle CDK inhibitors such as CDK4 and CDK6 (eg, palbociclib) is allowed
  • Known brain metastases or carcinomatous meningitis. Exception: previously treated brain metastatic disease that remains stable on MRI ? 4 weeks prior to enrollment, without steroids or anti-epileptic medications
  • History of allergic reactions attributed to compounds of similar chemical composition to SY-1365
  • Immunocompromised patients with increased risk of opportunistic infections, including known HIV-positive patients
  • Patients with known active Hepatitis B or Hepatitis C infection
  • Prior treatment (< 2 weeks before start of SY-1365) with moderate or strong CYP3A4 inducers or strong CYP3A4 inhibitors. See list in Appendix 3
  • Baseline QT interval corrected with Fridericia's method (QTcF) > 480 ms

Gender

All

Ages

18 Years and older

Accepts Healthy Volunteers

No

Study Locations and Contact Information (2)

Study Location Distance Name Phone Email
Dana Farber Cancer Institute - Boston, Massachusetts 2.4 miles None None None
South Texas Accelerated Research Therapeutics - San Antonio, Texas 1,768.2 miles None None None

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