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

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

Overview

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.

Interventions

• Drug GVV858
  Experimental
• Drug Fulvestrant
  Approved medication
• Drug Letrozole
  Approved medication

Primary outcome measures

• Phase I: Incidence and severity of dose-limiting toxicities (DLTs) [Time frame: 28 days]
• Phase I and phase II: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) [Time frame: Up to approximately 2 years]
• Phase I and phase II: Frequency of dose interruptions, reductions and discontinuations [Time frame: Up to approximately 2 years]
• Phase I and phase II: Dose intensity [Time frame: Up to approximately 2 years]

Secondary outcome measures (9)

• Phase I and II: Peak plasma concentration (Cmax) of GVV858 [Time frame: 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 [Time frame: 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 [Time frame: 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) [Time frame: Up to approximately 2 years]
• Phase I and Phase II: Best overall response (BOR) [Time frame: Up to approximately 2 years]
• Phase I and Phase II: Disease control rate (DCR) [Time frame: Up to approximately 2 years]
• Phase I and Phase II: Clinical benefit rate (CBR) [Time frame: Up to approximately 2 years]
• Phase I and Phase II: Progression free survival (PFS) [Time frame: Up to approximately 2 years]
• Phase II: Duration of response (DOR) [Time frame: Up to approximately 2 years]

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.

Other protocol-defined inclusion/exclusion criteria may apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 3 centers

• Emory University — Atlanta
• Tennessee Oncology PLLC — Nashville
• START — San Antonio

Germany · 2 centers

• Novartis Investigative Site — Jena
• Novartis Investigative Site — Essen

Italy · 2 centers

• Novartis Investigative Site — Milan
• Novartis Investigative Site — Milan

Spain · 2 centers

• Novartis Investigative Site — Barcelona
• Novartis Investigative Site — Madrid

Czechia · 1 center

• Novartis Investigative Site — Olomouc

Denmark · 1 center

• Novartis Investigative Site — Odense C

France · 1 center

• Novartis Investigative Site — Pierre-Bénite

Japan · 1 center

• Novartis Investigative Site — Kyoto

Singapore · 1 center

• Novartis Investigative Site — Singapore

Taiwan · 1 center

• Novartis Investigative Site — Taipei

Identifiers

NCT: NCT07288359 · CGVV858A12101 · 2025-521911-38

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗