Advanced HR+/HER2- Breast CancerPhase 1/2NCT07288359
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
A Phase 1/2 study testing GVV858, Fulvestrant and Letrozole in people with Advanced HR+/HER2- Breast Cancer and Advanced CCNE1-amplified Solid Tumors, run by Novartis Pharmaceuticals at 16 sites in 11 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced HR+/HER2- Breast Cancer, Advanced CCNE1-amplified Solid Tumors, Metastatic Castration-resistant Prostate Cancer
- What is being tested?
- GVV858, Fulvestrant and Letrozole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 205 participants
- Where
- 16 sitesin 11 countries
- Study dates
- 29 Dec 2025to 9 May 2031
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
16 sites in 11 countries. Contact the study team or a site near you to ask about taking part.
Novartis Pharmaceuticals contact
16 sites in 11 countries
United States3 sites, 3 recruiting
- Recruiting
Emory University
Atlanta, Georgia, 30322
Stacy Williams, stacy.d.williams@emory.edu
Elizabeth Sakach
- Recruiting
Tennessee Oncology PLLC
Nashville, Tennessee, 37203
Henry Black, hblack@tnonc.com
Jeffery Russell
- Recruiting
START
San Antonio, Texas, 78229
Edwin Blanco-Cepeda, +1 210 593 5250, edwin.blancocepeda@startresearch.com
Amita Patnaik
Germany2 sites, 2 recruiting
- Recruiting
Novartis Investigative Site
Essen, 45147
- Recruiting
Novartis Investigative Site
Jena, Thuringia, 07740
Italy2 sites, 2 recruiting
- Recruiting
Novartis Investigative Site
Milan, MI, 20141
- Recruiting
Novartis Investigative Site
Milan, MI, 20162
Spain2 sites, 2 recruiting
- Recruiting
Novartis Investigative Site
Barcelona, 08035
- Recruiting
Novartis Investigative Site
Madrid, 28041
Canada1 site, 1 recruiting
- Recruiting
Novartis Investigative Site
Toronto, Ontario, M4N 3M5
Czechia1 site, 1 recruiting
- Recruiting
Novartis Investigative Site
Olomouc, 779 00
Denmark1 site, 1 recruiting
- Recruiting
Novartis Investigative Site
Odense C, 5000
France1 site, 1 recruiting
- Recruiting
Novartis Investigative Site
Pierre-Bénite, 69495
Singapore1 site, 1 recruiting
- Recruiting
Novartis Investigative Site
Singapore, 168583
About this study
Official title: An Open-label, Multi-center, Phase I/II Study of GVV858 as a Single Agent and in Combination With Endocrine Therapy in Patients With Advanced Hormone Receptor Positive, HER2- Negative Breast Cancer and Other Advanced Solid Tumors
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.
Read the 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
- Being tested
- GVV858, Fulvestrant, Letrozole
- Keywords
- GVV858, Fulvestrant, Letrozole, Breast Cancer, CCNE1 amplification, Prostate Cancer
- Medical subject headings
- Breast Neoplasms, Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GVV858Drug
Experimental
FulvestrantDrug
Also called Faslodex
Approved medication
LetrozoleDrug
Also called Femara
Approved medication
| Study group | Role | What they receive |
|---|---|---|
| GVV858 Single Agent (Arm A) | Experimental | Phase I Receives: Drug: GVV858 |
| GVV858 in combination with fulvestrant (Arm B) | Experimental | Phase I Receives: Drug: GVV858; Drug: Fulvestrant |
| GVV858 in combination with letrozole (Arm C) | Experimental | Phase I Receives: Drug: GVV858; Drug: Letrozole |
| GVV858 in combination with fulvestrant (Arm D) | Experimental | Phase II, recommended dose regimen 1 Receives: Drug: GVV858; Drug: Fulvestrant |
| GVV858 in combination with fulvestrant (Arm E) | Experimental | Phase II, recommended dose regimen 2, optional dose optimization Receives: Drug: GVV858; Drug: Fulvestrant |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to approximately 2 years
Secondary outcomes (9)
Phase I and II: Peak plasma concentration (Cmax) of GVV858
Pharmacokinetic (PK) parameters calculated based on GVV858 plasma concentrations.
Measured: 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
PK parameters calculated based on GVV858 plasma concentrations.
Measured: 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
PK parameters calculated based on GVV858 plasma concentrations.
Measured: 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)
Tumor response assessed by the investigator based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), or Prostate Cancer Working Group 3 (PCWG3) criteria including PCWG3-modified RECIST v1.1. (only for patients with prostate cancer).
ORR per RECIST v1.1 is defined as the proportion of patients with a best overall response of Complete response (CR) or Partial response (PR) according to RECIST v1.1 as per local review.
Measured: Up to approximately 2 years
Phase I and Phase II: Best overall response (BOR)
Tumor response assessed by the investigator based on based on RECIST v1.1, or PCWG3 criteria including PCWG3-modified RECIST v1.1. (only for patients with prostate cancer).
BOR per RECIST v1.1 is defined as the best overall confirmed response recorded from the start of the treatment until progressive disease (PD), death, start of new therapy, withdrawal of consent or end of study, whatever comes first.
Measured: Up to approximately 2 years
Phase I and Phase II: Disease control rate (DCR)
Tumor response assessed by the investigator based on based on RECIST v1.1, or PCWG3 criteria including PCWG3-modified RECIST v1.1. (only for patients with prostate cancer).
DCR per RECIST v1.1 is defined as the proportion of patients with a BOR of CR, PR, or Stable disease (SD) according to RECIST v1.1 as per local review.
Measured: Up to approximately 2 years
Phase I and Phase II: Clinical benefit rate (CBR)
Tumor response assessed by the investigator based on based on RECIST v1.1, or PCWG3 criteria including PCWG3-modified RECIST v1.1. (only for patients with prostate cancer).
CBR per RECIST v1.1 is defined as the proportion of patients with a BOR of CR, PR, or an overall lesion response of SD or Non-CR/Non-PD which lasts for at least 24 weeks according to RECIST v1.1 as per local review.
Measured: Up to approximately 2 years
Phase I and Phase II: Progression free survival (PFS)
Tumor response assessed by the investigator based on based on RECIST v1.1, or PCWG3 criteria including PCWG3-modified RECIST v1.1. (only for patients with prostate cancer).
PFS per RECIST 1.1 is defined as the time from the date of start of study treatment (phase I) or the date of randomization (Phase II) to the date of the first documented progression or death due to any cause.
Measured: Up to approximately 2 years
Phase II: Duration of response (DOR)
Tumor response assessed by the investigator based on based on RECIST v1.1, or PCWG3 criteria including PCWG3-modified RECIST v1.1. (only for patients with prostate cancer).
DOR per RECIST v1.1 is the time between the first documented response (CR or PR) and the date of progression by local review as applicable or death due to any cause.
Measured: Up to approximately 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2025
- Study start29 Dec 2025
- Primary completion9 May 2031 (estimated)
- Study completion9 May 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced HR+/HER2- Breast CancerStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 205 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07288359
- Sponsor's protocol ID
- CGVV858A12101
- Other IDs
- 2025-521911-38, 2025
- Status last verified
- Oct 2026
- First submitted
- 15 Dec 2025
- Last updated
- 9 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.