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.
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.
Eligibility
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.