Testing the Safety of the Combination of Anti-Cancer Drugs CX-5461 (Pidnarulex) and Trastuzumab Deruxtecan (T-DXd) for Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Solid Tumors and Breast Cancer

Summary

This phase I trial tests the safety, side effects, and best dose of pidnarulex in combination with trastuzumab deruxtecan in treating patients with breast cancer and other solid tumors that express varying levels of a protein called HER2 and that has spread from where it first started (primary site) to other places in the body (metastatic), that cannot be removed by surgery (unresectable), or that has spread to nearby tissue or lymph nodes (locally advanced). Pidnarulex is an enzyme inhibitor that causes cell death and prevents tumor cell growth. Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates. It is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive tumor cells in a targeted way and delivers deruxtecan to kill them. Giving pidnarulex in combination with trastuzumab deruxtecan may be safe, tolerable and/or effective in treating patients with metastatic, unresectable, or locally advanced HER2-expressing breast cancer or other solid tumors.

Conditions

• Anatomic Stage III Breast Cancer AJCC v8
• Anatomic Stage IV Breast Cancer AJCC v8
• Invasive Breast Carcinoma
• Locally Advanced Breast Carcinoma
• Metastatic Breast Carcinoma
• Metastatic HER2-Low Breast Carcinoma
• Metastatic HER2-Positive Breast Carcinoma
• Metastatic Hormone Receptor-Positive Breast Carcinoma
• Metastatic Malignant Solid Neoplasm
• Metastatic Triple-Negative Breast Carcinoma
• Unresectable Breast Carcinoma
• Unresectable HER2-Low Breast Carcinoma
• Unresectable HER2-Positive Breast Carcinoma
• Unresectable Hormone Receptor-Positive Breast Carcinoma
• Unresectable Malignant Solid Neoplasm
• Unresectable Triple-Negative Breast Carcinoma

Interventions

PROCEDURE

Biopsy Procedure

Undergo biopsy

PROCEDURE

Biospecimen Collection

Undergo collection of blood samples

PROCEDURE

Echocardiography Test

Undergo ECHO

PROCEDURE

Multigated Acquisition Scan

Undergo MUGA

DRUG

Pidnarulex

Given IV

PROCEDURE

Radiologic Imaging Procedure

Undergo radiologic imaging

BIOLOGICAL

Trastuzumab Deruxtecan

Given IV

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Filipa Lynce · Dana-Farber - Harvard Cancer Center LAO

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-10-05

Primary Completion

2028-01-10

Completion

2028-01-10

FDA Drug

Yes

Countries

• United States

Study Locations