Study of ERW316 as a Single Agent or in Combination With Endocrine Therapy in Patients With HR+/HER2- Breast Cancer and Other Advanced Solid Tumors

An Open-label, Multi-center, Phase I/II Study of ERW316 as a Single Agent or in Combination With Endocrine Therapy in Patients With HR+/HER2- Breast Cancer and Other Advanced Solid Tumors

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Castration-resistant Prostate Cancer (mCRPC); Advanced HR+/HER2- Breast Cancer; Advanced CCNE1-amplified Solid Tumors
• Intervention / Treatment: Drug: ERW316; Drug: Fulvestrant; Drug: Letrozole

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 217
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: 1-888-669-6682; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals; Phone Number: +41613241111

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase I: ERW316 single agent (Arm A); ERW316	Drug: ERW316; Oral administration
Experimental: Phase I: ERW316 in combination with Fulvestrant (Arm B); ERW316 in combination with fulvestrant.	Drug: ERW316; Oral administration; Drug: Fulvestrant; Intramuscular injection. Approved medication.; Other Names: Faslodex
Experimental: Phase I: ERW316 in combination with letrozole (Arm C); ERW316 in combination with letrozole.	Drug: ERW316; Oral administration; Drug: Letrozole; Oral administration. Approved medication.; Other Names: Femara
Experimental: Phase II, recommended dose (RD)-1: ERW316 in combination with Fulvestrant (Arm D); ERW316 in combination with fulvestrant.	Drug: ERW316; Oral administration; Drug: Fulvestrant; Intramuscular injection. Approved medication.; Other Names: Faslodex
Experimental: Phase II, RD-2 (optional dose optimization): ERW316 in combination with Fulvestrant (Arm E); ERW316 in combination with fulvestrant.	Drug: ERW316; Oral administration; Drug: Fulvestrant; Intramuscular injection. Approved medication.; Other Names: Faslodex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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, 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 I part. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.	28 days
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 laboratory values, vital signs and echocardiograms (ECGs) qualifying and reported as AEs.	Up to approximately 2 years
Phase I and Phase II: Frequency of dose interruptions, reductions and discontinuations	Number of participants with dose adjustments (interruptions, reductions, or permanent discontinuation) as a measure of tolerability.	Up to approximately 2 years
Phase I and Phase II: Dose intensity	Dose intensity defined as the ratio of actual cumulative dose received and actual duration of exposure.	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I and Phase II: Best Overall Response (BOR)	BOR per RECIST v1.1 is defined as the best overall confirmed response recorded from the start of the treatment until progressive disease (PD), death, start of new therapy, withdrawal of consent or end of study, whatever comes first. Efficacy will be based on the investigator assessment per 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).	Up to approximately 2 years
Phase I and Phase II: Overall Response Rate (ORR)	ORR per RECIST v1.1 is defined as the proportion of patients with a BOR of Complete response (CR) or Partial response (PR). Efficacy will be based on the investigator assessment per RECIST v1.1, or PCWG3 criteria including PCWG3-modified RECIST v1.1 (only for patients with prostate cancer).	Up to approximately 2 years
Phase I and Phase II: Disease Control Rate (DCR)	DCR per RECIST v1.1 is defined as the proportion of patients with a BOR of CR, PR, or Stable disease (SD). Efficacy will be based on the investigator assessment per RECIST v1.1, or PCWG3 criteria including PCWG3-modified RECIST v1.1 (only for patients with prostate cancer).	Up to approximately 2 years
Phase I and Phase II: Clinical Benefit Rate (CBR)	CBR per RECIST v1.1 is defined as the proportion of patients with a BOR of CR, PR, or an overall lesion response of SD or Non-CR/Non-PD which lasts for at least 24 weeks. Efficacy will be based on the investigator assessment per RECIST v1.1, or PCWG3 criteria including PCWG3-modified RECIST v1.1 (only for patients with prostate cancer).	Up to approximately 2 years
Phase I and Phase II: Progression Free Survival (PFS)	PFS per RECIST 1.1 is defined as the time from the date of start of study treatment (Phase I) or the date of randomization (Phase II) to the date of the first documented progression or death due to any cause. Efficacy will be based on the investigator assessment per RECIST v1.1, or PCWG3 criteria including PCWG3-modified RECIST v1.1 (only for patients with prostate cancer).	Up to approximately 2 years
Phase II: Duration of Response (DOR)	DOR per RECIST v1.1 is the time between the first documented response (CR or PR) and the date of progression by local review as applicable or death due to any cause. Efficacy will be based on the investigator assessment per RECIST v1.1, or PCWG3 criteria including PCWG3-modified RECIST v1.1 (only for patients with prostate cancer).	Up to approximately 2 years
Phase I and Phase II: Area under the plasma concentration-time curve (AUC) of ERW316	Pharmacokinetic (PK) parameters based on plasma concentrations of ERW316.	From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 22. 1 cycle = 28 days
Phase I and Phase II: Maximum plasma concentration (Cmax) of ERW316	PK parameters based on plasma concentrations of ERW316.	From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 22. 1 cycle = 28 days
Phase I and Phase II: Time to reach maximum plasma concentration (Tmax) of ERW316	PK parameters based on plasma concentrations of ERW316.	From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 22. 1 cycle = 28 days

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): June 30, 2026
• Primary Completion (Estimated): August 1, 2031
• Study Completion (Estimated): August 1, 2031

Study Registration Dates

• First Submitted: April 30, 2026
• First Submitted That Met QC Criteria: April 30, 2026
• First Posted (Actual): May 6, 2026

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Breast cancer; Prostate cancer; hormone receptor positive; letrozole; fulvestrant; HER-2 negative; CCNE1 amplification; ERW316
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Prostatic Neoplasms; Breast Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Nitriles; Estradiol; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Triazoles; Letrozole; Fulvestrant
• Other Study ID Numbers: CERW316A12101; 2025-521913-16 (Registry Identifier: EU registry CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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/.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No