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

Novartis

Status and phase: Enrolling; Phase 2; Phase 1

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

Treatments: Drug: Letrozole; Drug: GVV858; Drug: Fulvestrant

Study type: Interventional

Funder types: Industry

Identifiers

NCT07288359

CGVV858A12101

2025-521911-38 (Other Identifier)

2025

Details and patient eligibility

About

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.

Full 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.

Enrollment: 205 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 (mCRPC), with no documented neuroendocrine component, castrate level of testosterone. For dose expansion only: 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.
  • 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 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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205 participants in 5 patient groups

GVV858 Single Agent (Arm A)

Experimental group

Description:

Phase I

Treatment:

Drug: GVV858

GVV858 in combination with fulvestrant (Arm B)

Experimental group

Description:

Phase I

Treatment:

Drug: Fulvestrant

Drug: GVV858

GVV858 in combination with letrozole (Arm C)

Experimental group

Description:

Phase I

Treatment:

Drug: GVV858

Drug: Letrozole

GVV858 in combination with fulvestrant (Arm D)

Experimental group

Description:

Phase II, recommended dose regimen 1 (optional dose optimization)

Treatment:

Drug: Fulvestrant

Drug: GVV858

GVV858 in combination with fulvestrant (Arm E)

Experimental group

Description:

Phase II, recommended dose regimen 2 (optional dose optimization)

Treatment:

Drug: Fulvestrant

Drug: GVV858