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

NCT ID: NCT07288359

Last Updated: 2026-02-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 205 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-29
• Study Completion Date: 2031-05-09

Brief Summary

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.

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

GVV858 Single Agent (Arm A)

Phase I

Group Type: EXPERIMENTAL

GVV858

Intervention Type: DRUG

Experimental

GVV858 in combination with fulvestrant (Arm B)

Phase I

Group Type: EXPERIMENTAL

GVV858

Intervention Type: DRUG

Experimental

Fulvestrant

Intervention Type: DRUG

Approved medication

GVV858 in combination with letrozole (Arm C)

Phase I

Group Type: EXPERIMENTAL

GVV858

Intervention Type: DRUG

Experimental

Letrozole

Intervention Type: DRUG

Approved medication

GVV858 in combination with fulvestrant (Arm D)

Phase II, recommended dose regimen 1

Group Type: EXPERIMENTAL

GVV858

Intervention Type: DRUG

Experimental

Fulvestrant

Intervention Type: DRUG

Approved medication

GVV858 in combination with fulvestrant (Arm E)

Phase II, recommended dose regimen 2, optional dose optimization

Group Type: EXPERIMENTAL

GVV858

Intervention Type: DRUG

Experimental

Fulvestrant

Intervention Type: DRUG

Approved medication

Interventions

GVV858

Experimental

Intervention Type: DRUG

Fulvestrant

Approved medication

Intervention Type: DRUG

Letrozole

Approved medication

Intervention Type: DRUG

Other Intervention Names

Faslodex; Femara

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Tennessee Oncology PLLC

Nashville, Tennessee, United States

Site Status: RECRUITING

Novartis Investigative Site

Singapore, , Singapore

Site Status: RECRUITING

Novartis Investigative Site

Taipei, , Taiwan

Site Status: RECRUITING

Countries

United States; Singapore; Taiwan

Central Contacts

Novartis Pharmaceuticals

Role: CONTACT

novartis.email@novartis.com

1-888-669-6682

Novartis Pharmaceuticals

Role: CONTACT

+41613241111

Facility Contacts

Caitlin J Pecknold

Role: primary

cpecknold@tnonc.com

Other Identifiers

2025-521911-38

Identifier Type: OTHER

Identifier Source: secondary_id

CGVV858A12101

Identifier Type: -

Identifier Source: org_study_id