Testing the Combination of Two Anti-cancer Drugs, DS-8201a and AZD6738, for The Treatment of Advanced Solid Tumors Expressing the HER2 Protein or Gene, The DASH Trial

Summary

The dose escalation phase of this trial identifies the safety, side effects and best dose of ceralasertib (AZD6738) when given in combination with trastuzumab deruxtecan (DS-8201a) in treating patients with solid tumors that have a change (mutation) in the HER2 gene or protein and have spread to other places in the body (advanced). The dose expansion phase (phase Ib) of this trial compares how colorectal and gastroesophageal cancers with HER2 mutation respond to treatment with a combination of ceralasertib and trastuzumab deruxtecan versus trastuzumab deruxtecan alone. Ceralasertib may stop the growth of tumor cells and may kill them by blocking some of the enzymes needed for cell growth. Trastuzumab deruxtecan is a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive cancer cells in a targeted way and delivers deruxtecan to kill them. Ceralasertib and trastuzumab deruxtecan may be safe, tolerable and effective in treating patients with advanced solid tumors expressing the HER2 protein or gene.

Conditions

• Advanced Breast Carcinoma
• Advanced Colon Carcinoma
• Advanced Colorectal Carcinoma
• Advanced Endometrial Carcinoma
• Advanced Gastric Carcinoma
• Advanced Gastroesophageal Junction Adenocarcinoma
• Advanced Malignant Solid Neoplasm
• Advanced Salivary Gland Carcinoma
• Anatomic Stage III Breast Cancer AJCC v8
• Anatomic Stage IV Breast Cancer AJCC v8
• Clinical Stage III Gastric Cancer AJCC v8
• Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8
• Clinical Stage IV Gastric Cancer AJCC v8
• Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8
• HER2-Positive Breast Carcinoma
• Malignant Hepatobiliary Neoplasm
• Metastatic Breast Carcinoma
• Metastatic Colon Carcinoma
• Metastatic Colorectal Carcinoma
• Metastatic Endometrial Carcinoma
• Metastatic Gastric Carcinoma
• Metastatic Gastroesophageal Junction Adenocarcinoma
• Metastatic Malignant Solid Neoplasm
• Metastatic Salivary Gland Carcinoma
• Stage III Colon Cancer AJCC v8
• Stage III Colorectal Cancer AJCC v8
• Stage III Major Salivary Gland Cancer AJCC v8
• Stage III Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8
• Stage IV Colon Cancer AJCC v8
• Stage IV Colorectal Cancer AJCC v8
• Stage IV Major Salivary Gland Cancer AJCC v8
• Stage IV Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8
• Unresectable Breast Carcinoma
• Unresectable Colon Carcinoma
• Unresectable Colorectal Carcinoma
• Unresectable Endometrial Carcinoma
• Unresectable Gastric Carcinoma
• Unresectable Gastroesophageal Junction Adenocarcinoma
• Unresectable Malignant Solid Neoplasm
• Unresectable Salivary Gland Carcinoma

Interventions

PROCEDURE

Biopsy Procedure

Undergo tissue biopsy

PROCEDURE

Biospecimen Collection

Undergo blood sample collection

DRUG

Ceralasertib

Given PO

PROCEDURE

Computed Tomography

Undergo CT or PET/CT

PROCEDURE

Echocardiography Test

Undergo ECHO

PROCEDURE

Multigated Acquisition Scan

Undergo MUGA

PROCEDURE

Positron Emission Tomography

Undergo PET/CT

BIOLOGICAL

Trastuzumab Deruxtecan

Given IV

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Kanwal P Raghav · University of Texas MD Anderson 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

2021-08-09

Primary Completion

2027-03-31

Completion

2027-03-31

FDA Drug

Yes

Countries

• United States

Study Locations