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.
Age ≥ 18 years old.
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.
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.
Sequential
GVV858
DrugExperimental
Fulvestrant
DrugApproved medication
Letrozole
DrugApproved medication
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.
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.
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.
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.
Phase I and II: Peak plasma concentration (Cmax) of GVV858
Pharmacokinetic (PK) parameters calculated based on GVV858 plasma concentrations.
Phase I and II: Time to reach peak plasma concentration (Tmax) of GVV858
PK parameters calculated based on GVV858 plasma concentrations.
Phase I and II: Area under the plasma concentration-time curve (AUC) of GVV858
PK parameters calculated based on GVV858 plasma concentrations.
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.
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