Advanced HR+/HER2- Breast CancerAdvanced CCNE1-amplified Solid TumorsMetastatic Castration-resistant Prostate Cancer
Investigational drug(s) / intervention(s)
GVV858FulvestrantLetrozole
GVV858: Experimental
Fulvestrant: Approved medication
Letrozole: Approved medication
Study 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
Primary outcome measure(s)
Phase I: Incidence and severity of dose-limiting toxicities (DLTs) — 28 days 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.
Phase I and phase II: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) — Up to approximately 2 years Number of participants with AEs and SAEs, including changes in vital signs, electrocardiograms (ECGs) and laboratory values qualifying and reported as AEs.
Phase I and phase II: Frequency of dose interruptions, reductions and discontinuations — Up to approximately 2 years Number of participants with dose adjustments (reductions, interruption, or permanent discontinuation) as a measure of tolerability.
Phase I and phase II: Dose intensity — Up to approximately 2 years The dose intensity of each study drug is computed as the ratio of actual cumulative dose received and actual duration of exposure.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
We use cookies to analyse site traffic and improve your experience. With your consent, we may also use cookies for advertising. You can change your choice at any time on our Cookie Policy page. See also our Privacy Policy.