Business decision

Phase I: Characterize safety and tolerability of ERW316 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 ERW316 in combination with fulvestrant in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer.

This is a first-in-human, open-label, Phase I/II, multi-center study consisting of an ERW316 single agent 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 ERW316 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.

Inclusion Criteria:

• Age ≥ 18 years old
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
• Patients with one of the following histologically or cytologically confirmed advanced cancers:

Phase I (patients with one of the following cancers, for 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 CCNE1- amplification. For dose expansion only: no more than 5 prior lines of therapy (ovarian cancer) or 3 prior lines of therapy (gastric or esophageal adenocarcinoma).
• Metastatic castration-resistant prostate adenocarcinoma (mCRPC), with no documented neuroendocrine component, castrate level of testosterone, disease progression on or after 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- 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 total lines of endocrine therapy and no prior cytotoxic chemotherapy or antibody-drug conjugate therapy for advanced disease.

Phase I and Phase II:

- 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

Exclusion Criteria:

• Patients with inadequate bone marrow and/or organ function
• 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 breast cancer only: Patient is concurrently using hormone replacement therapy.
• Women of childbearing potential (WOCBP) who are unwilling to use highly effective contraception methods
• Pregnant or nursing women

Other protocol-defined inclusion/exclusion criteria may apply.

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.