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

Prior treatment

• 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.
• For patients with breast cancer only: Patient is concurrently using hormone replacement therapy. Pre/perimenopausal women or men with breast cancer who are unwilling or unable to be treated with a Luteinizing Hormone-Releasing Hormone (LHRH) agonist (goserelin or leuprolide) for gonadal suppression, as per locally approved label (see Protocol Section 6.1.1).

Other illness

• Patients with symptomatic visceral disease, including visceral crisis.

Other

• Patients with inadequate bone marrow and/or organ function.
• Women of childbearing potential (WOCBP) who are unwilling to use highly effective contraception methods.
• Pregnant or nursing women.

• Age ≥ 18 years old.
• Phase I, Dose escalation: Patients with one of the following histologically or cytologically confirmed advanced cancers, for whom no standard therapy is available or appropriate in the judgement of the investigator: HR+/HER2- advanced breast cancer (aBC) with disease progression on or following, or have been intolerant to, at least one line of hormone-based therapy in combination with a CDK4/6i for advanced disease (or during or within 12 months of completing adjuvant endocrine therapy (ET) plus CDK4/6i therapy), and at least one additional line of systemic therapy for metastatic disease. Locally advanced or metastatic solid malignancy with CCNE-1 amplification.
• Phase I, Dose expansion: Patients with one of the following histologically or cytologically confirmed advanced cancers, for whom no standard therapy is available or appropriate in the judgement of the investigator: HR+/HER2- aBC with disease progression on or following, or have been intolerant to, at least one line of hormone-based therapy in combination with a CDK4/6i for advanced disease (or during or within 12 months of completing adjuvant ET plus CDK4/6i therapy), and at least one additional line of systemic therapy for metastatic disease. Advanced or metastatic ovarian cancer (OC) with CCNE-1 amplification, following progression on or after, or intolerance to, standard-of-care (SOC) therapy. Advanced or metastatic gastric or esophageal adenocarcinoma (GEA) with CCNE-1 amplification, following progression on or after, or intolerance to, SOC therapy. Metastatic castration-resistant prostate cancer (mCRPC) with disease progression on or after, or intolerance to, at least one line of androgen receptor pathway inhibitor therapy (ARPI) and at least one line of taxane-based chemotherapy, and no more than 3 total prior lines of systemic therapy for metastatic disease.
• Phase II: HR+/HER2- a BC with disease progression on or after an endocrine therapy in combination with a CDK4/6 inhibitor for advanced disease, with no more than 2 total lines of endocrine therapy for advanced disease, and no prior cytotoxic chemotherapy or antibody-drug conjugate therapy for advanced disease.
• Measurable disease as determined by RECIST v1.1, with the following exceptions: aBC 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. mCRPC only: If no measurable disease is present per PCWG3 modified RECIST, then at least one metastatic lesion must be present on bone scan imaging obtained prior to C1D1.