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

NCT07288359 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: CGVV858A121012025-521911-38
• Study Type: interventional
• Target: 205
• Locations: 4 countries
• Sites: 4

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.

Conditions

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

Keywords

GVV858; Fulvestrant; Letrozole; Breast Cancer; CCNE1 amplification; Prostate Cancer

Outcome Measures

Primary Outcomes (4)

• Phase I: Incidence and severity of dose-limiting toxicities (DLTs)

  Number of participants with DLTs. A DLT is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher, unless clearly and inconvertibly assessed as due to disease progression, inter-current illness/injury, concomitant medications, or extraneous causes, that occurs within the first 28 days of treatment in the Phase 1 part. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.

  28 days

• Phase I and phase II: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)

  Number of participants with AEs and SAEs, including changes in vital signs, electrocardiograms (ECGs) and laboratory values qualifying and reported as AEs.

  Up to approximately 2 years

• Phase I and phase II: Frequency of dose interruptions, reductions and discontinuations

  Number of participants with dose adjustments (reductions, interruption, or permanent discontinuation) as a measure of tolerability.

  Up to approximately 2 years

• Phase I and phase II: Dose intensity

  The dose intensity of each study drug is computed as the ratio of actual cumulative dose received and actual duration of exposure.

  Up to approximately 2 years

Secondary Outcomes (9)

• Phase I and II: Peak plasma concentration (Cmax) of GVV858

  Cycle 1 Day 1 and/or Day 21: From pre-dose up to maximum 24 hours post dose. The duration of one cycle is 28 days.

• Phase I and II: Time to reach peak plasma concentration (Tmax) of GVV858

  Cycle 1 Day 1 and/or Day 21: From pre-dose up to maximum 24 hours post dose. The duration of one cycle is 28 days.

• Phase I and II: Area under the plasma concentration-time curve (AUC) of GVV858

  Cycle 1 Day 1 and/or Day 21: From pre-dose up to maximum 24 hours post dose. The duration of one cycle is 28 days.

• Phase I and Phase II: Overall response rate (ORR)

  Up to approximately 2 years

• Phase I and Phase II: Best overall response (BOR)

  Up to approximately 2 years

Study Arms (5)

GVV858 Single Agent (Arm A)

EXPERIMENTAL

Phase I

Drug: GVV858

GVV858 in combination with fulvestrant (Arm B)

EXPERIMENTAL

Phase I

Drug: GVV858; Drug: Fulvestrant

GVV858 in combination with letrozole (Arm C)

EXPERIMENTAL

Phase I

Drug: GVV858; Drug: Letrozole

GVV858 in combination with fulvestrant (Arm D)

EXPERIMENTAL

Phase II, recommended dose regimen 1

Drug: GVV858; Drug: Fulvestrant

GVV858 in combination with fulvestrant (Arm E)

EXPERIMENTAL

Phase II, recommended dose regimen 2, optional dose optimization

Drug: GVV858; Drug: Fulvestrant

Interventions

GVV858 DRUG

Experimental

GVV858 Single Agent (Arm A); GVV858 in combination with fulvestrant (Arm B); GVV858 in combination with fulvestrant (Arm D); GVV858 in combination with fulvestrant (Arm E); GVV858 in combination with letrozole (Arm C)

Fulvestrant DRUG

Approved medication

Also known as: Faslodex

GVV858 in combination with fulvestrant (Arm B); GVV858 in combination with fulvestrant (Arm D); GVV858 in combination with fulvestrant (Arm E)

Letrozole DRUG

Approved medication

Also known as: Femara

GVV858 in combination with letrozole (Arm C)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (4)

Tennessee Oncology PLLC

Nashville, Tennessee, 37203, United States

RECRUITING

Novartis Investigative Site

Kyoto, 6068507, Japan

RECRUITING

Novartis Investigative Site

Singapore, 168583, Singapore

RECRUITING

Novartis Investigative Site

Taipei, 10002, Taiwan

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Prostatic Neoplasms

Interventions

Fulvestrant; Letrozole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

1-888-669-6682; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

+41613241111

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2025
• First Posted: December 17, 2025
• Study Start: December 29, 2025
• Primary Completion (Estimated): April 24, 2031
• Study Completion (Estimated): May 9, 2031
• Last Updated: February 23, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

US (1); JP (1); TW (1); SG (1)