Clinical Trial 23756

• Overview

  Study Title:

  A Phase Ib/II Multicenter, Open-Label, Randomized Study Evaluating the Safety, Pharmacokinetics, and Activity of GDC-4198 Alone and in Combination with Giredestrant in Comparison with Abemaciclib and Giredestrant in Participants with Locally Advanced or Metastatic Estrogen Receptor-Positive, HER2-Negative Breast Cancer Who Have Previously Progressed During or After a CDK4/6 Inhibitor

  Summary:

  The purpose of this study is to assess the safety of GDC-4198 alone and in combination with giredestrant and also the efficacy of GDC-4198 + giredestrant versus abemaciclib + giredestrant in participants with locally advanced or metastatic ER+, HER2- breast cancer. The study consists of 2 phases: Phase Ib and Phase II. Phase Ib will evaluate the safety and pharmacokinetics (PK) of GDC-4198 alone and in combination with giredestrant. Phase II stage will compare the activity and safety of GDC-4198 and giredestrant with abemaciclib and giredestrant.

  Objective:

  Primary Objectives Phase Ib Stage -To evaluate the safety of GDC-4198 alone and in combination with giredestrant. Phase II Stage -To compare the efficacy of two dose levels of GDC-4198 in combination with giredestrant to the efficacy of abemaciclib in combination with giredestrant. Secondary Objectives Phase Ib Stage -To make a preliminary assessment of the activity of GDC-4198 alone or in combination with giredestrant. -To evaluate food-effect on the pharmacokinetics of GDC-4198 and its metabolites. Phase II Stage -To compare the efficacy of two dose levels of GDC-4198 in combination with giredestrant to the efficacy of abemaciclib in combination with giredestrant. -To compare the safety of two doses of GDC-4198 in combination with giredestrant to the safety of abemaciclib in combination with giredestrant. -To characterize the pharmacokinetics of GDC-4198 and its metabolites in combination with giredestrant -To identify a recommended dose of GDC-4198 for subsequent studies

• Treatments

  Therapies:

  CDK2 Inhibitor; CDK4/6 Inhibitor; Selective estrogen receptor degrader, SERD

  Medications:

  Abemaciclib (); GDC-4198 (); Giredestrant (); LY2835219 (Abemaciclib)

• Inclusion Criteria

  Key Inclusion Criteria:
  • Histologically and/or cytologically confirmed adenocarcinoma of the breast that is locally advanced or metastatic.
  • Previously documented ER+ and HER2- tumor according to American Society of Clinical Oncology (ASCO)/ College of American Pathologists (CAP) or European Society of Medical Oncology (ESMO) guidelines or any national guidelines with criteria conforming to ASCO/CAP or ESMO guidelines.
  • Disease progression during or after treatment with an approved cyclin-dependent kinase 4/6 (CDK4/6) inhibitor and endocrine therapy (ET) in the locally advanced or metastatic setting.
  • Measurable or non-measurable evaluable, disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Life expectancy ≥ 6 months

• Exclusion Criteria

  Key Exclusion Criteria:
  • Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term appropriate for treatment with cytotoxic chemotherapy at time of entry into the study, as per national or local treatment guidelines.
  • Have received more than one-line of therapy for locally advanced or metastatic disease.
  • Have received prior chemotherapy for metastatic breast cancer
  • Treatment with anti-cancer therapies, including investigational therapies, within 28 days or 5 drug elimination half -lives, whichever is shorter, prior to initiation of study drug. Treatment with an approved oral endocrine therapy (ET) within 7 days prior to initiation of study drug; treatment with fulvestrant or an approved CDK4/6 inhibitor within 21 days prior to initiation of study drug.
  • Poor peripheral venous access
  • Malabsorption condition or other gastrointestinal (GI) conditions/surgeries that the investigator assesses may significantly interfere with enteral absorption
  • History of malignancy within 3 years prior to screening, except for cancer under investigation in this study and malignancies with a negligible risk of metastasis or death.

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