Study of GVV858 as a Single Agent or in Combination With Endocrine Therapy in Patients With HR+/HER2- Breast Cancer and Other Advanced Solid Tumors

Purpose

Phase I: Characterize safety and tolerability of GVV858 as a single agent and in combination with fulvestrant or letrozole. Identify dose range for optimization/recommended dose for further clinical evaluation. Phase II: Further characterize the safety and tolerability of GVV858 in combination with fulvestrant in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer.

Conditions

  • Advanced HR+/HER2- Breast Cancer
  • Advanced CCNE1-amplified Solid Tumors
  • Metastatic Castration-resistant Prostate Cancer

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Age ≥ 18 years old. - Patients with one of the following histologically or cytologically confirmed advanced cancers: Phase I (patients with one of the following cancers, from whom no standard therapy is available or appropriate in the judgment of the investigator): - HR+/HER2- advanced breast cancer (aBC) with disease progression on or following at least one line of hormone-based therapy in combination with a CDK4/6i and at least one additional line of systemic therapy for metastatic disease. - Locally advanced or metastatic cancer with a CCNE1 amplification. For dose expansion only: no more than 3 prior lines of therapy for advanced or metastatic disease. - Metastatic castration-resistant prostate adenocarcinoma, with no documented neuroendocrine component, castrate level of testosterone, and no more than 3 prior lines of systemic therapy for metastatic disease. Phase II: - HR+/HER2- aBC with disease progression on or after an endocrine therapy in combination, with a CDK4/6 inhibitor for advanced disease with no more than 2 lines of endocrine therapy and no prior cytotoxic chemotherapy or antibody-drug-conjugate for advanced disease. - Measurable disease as determined by RECIST v1.1. - BC only: If no measurable disease is present, then at least one predominantly lytic bone lesion must be present that can be accurately assessed at baseline and is suitable for repeated assessment. - metastatic Castration-Resistant Prostate Cancer (mCRPC) only: If no measurable disease is present per PCWG3 modified RECIST, then at least 1 metastatic lesion must be present on bone scan imaging.

Exclusion Criteria

  • Patients with inadequate bone marrow and/or organ functions with out-of-range laboratory values. - Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality including myocardial infarction (MI), coronary artery bypass graft (CABG), long QT syndrome, or risk factors for Torsades de Pointes (TdP). - Presence of symptomatic central nervous system (CNS) metastases or CNS metastases that require local therapy or increasing doses of corticosteroids within 2 weeks prior to study entry. - Patients with symptomatic visceral disease, including visceral crisis. - For patients with BC: Patient is concurrently using hormone replacement therapy. - Women of childbearing potential who are unwilling to use highly effective contraception methods, pregnant or nursing women. Other protocol-defined inclusion/exclusion criteria may apply.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
GVV858 Single Agent (Arm A) 		Phase I
  • Drug: GVV858
    Experimental
Experimental
GVV858 in combination with fulvestrant (Arm B) 		Phase I
  • Drug: GVV858
    Experimental
  • Drug: Fulvestrant
    Approved medication
    Other names:
    • Faslodex
Experimental
GVV858 in combination with letrozole (Arm C) 		Phase I
  • Drug: GVV858
    Experimental
  • Drug: Letrozole
    Approved medication
    Other names:
    • Femara
Experimental
GVV858 in combination with fulvestrant (Arm D) 		Phase II, recommended dose regimen 1
  • Drug: GVV858
    Experimental
  • Drug: Fulvestrant
    Approved medication
    Other names:
    • Faslodex
Experimental
GVV858 in combination with fulvestrant (Arm E) 		Phase II, recommended dose regimen 2, optional dose optimization
  • Drug: GVV858
    Experimental
  • Drug: Fulvestrant
    Approved medication
    Other names:
    • Faslodex

Recruiting Locations

Tennessee Oncology PLLC
Nashville, Tennessee 37203
Contact:
Henry Black
hblack@tnonc.com

More Details

Status
Recruiting
Sponsor
Novartis Pharmaceuticals

Study Contact

Novartis Pharmaceuticals
1-888-669-6682
novartis.email@novartis.com

Detailed Description

This is a first-in-human, open-label, phase I/II, multi-center study consisting of a GVV858 single agent treatment arm in patients with advanced HR+/HER2- breast cancer, other advanced solid tumors harboring CCNE1 amplification, and metastatic castration-resistant prostate cancer, and a combination treatment arm of GVV858 with fulvestrant or letrozole in patients with advanced HR+/HER2- breast cancer. Single agent escalation may be followed by an expansion part stratified by disease indication. The escalation of the fulvestrant combination arm may continue into a randomized, open label, Phase II with optional dose optimization in advanced HR+/HER2- breast cancer patients.