Optimizing Antibody-Drug Conjugate Therapy Through Molecular Analysis for Therapy Choice (ADC MATCH)
Study Description
This phase II ADC MATCH screening and multi-sub-study treatment trial is evaluating whether biomarker-directed treatment with one of three antibody-drug conjugates (ADCs) (sacituzumab govitecan, enfortumab vedotin, and trastuzumab deruxtecan) works in treating patients with solid tumor cancers that have high expression of the Trop-2, nectin-4, or HER2 proteins and that may have spread from where they first started (primary site) to nearby tissue, lymph nodes, or distant parts of the body (advanced) or to other places in the body (metastatic). Precision medicine is a form of medicine that uses information about a person's genes, proteins, and environment to prevent, diagnose, or treat disease in a way that is tailored to the patient. ADCs such as sacituzumab govitecan, enfortumab vedotin, and trastuzumab deruxtecan are monoclonal antibodies attached to biologically active drugs and are a form of targeted therapy. Sacituzumab govitecan is a monoclonal antibody, called sacituzumab, linked to a drug called govitecan. Sacituzumab attaches to a protein called Trop-2 on the surface of tumor cells and delivers govitecan to kill them. Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to an anticancer drug called vedotin. It works by helping the immune system to slow or stop the growth of tumor cells. Enfortumab attaches to a protein called nectin-4 on tumor cells in a targeted way and delivers vedotin to kill them. Trastuzumab deruxtecan 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. Personalized treatment with sacituzumab govitecan, enfortumab vedotin, or trastuzumab deruxtecan may be an effective treatment option for patients with advanced or metastatic solid tumors that screen positive for high expression of Trop-2, nectin-4, or HER2, respectively.
Eligibility
SCREENING PROTOCOL INCLUSION CRITERIA:
-Patients must have histologically confirmed solid tumor requiring therapy and meet one of the following criteria:
-Patients must have disease not amenable to curative-intent therapy AND
-Patients who have had disease progression after treatment with all available therapies for their disease that are known to confer benefit or are intolerant to such treatment will be eligible, if other eligibility criteria are met. If the patient is currently receiving therapy without progression, the clinician must have assessed that the current therapy is no longer benefitting the patient, or that the patient is not tolerating the therapy. Patients can be screened on ADC MATCH if they have had three or fewer-lines of chemotherapy in the advanced/metastatic setting and are expected to need a treatment change within 6 months, and ADC MATCH is felt to be appropriate next line therapy AND
-Patients with disease for which no standard treatment exists that has been shown to confer benefit OR
-Patients who are willing to forego standard therapies known to confer benefit
NOTE: Patients can be on therapy at the time of initiating the Screening Protocol if the patient is interested in treatment on ADC MATCH upon progression, and the physician deems this appropriate
-Age at least 18 years.
-Women of childbearing potential must not be known to be pregnant. Pregnancy testing is not required
ADDITIONAL INCLUSION CRITERIA FOR TREATMENT COHORTS:
-Women of childbearing potential must have a negative serum pregnancy test result at treatment cohort screening
-Patients should have received no more than 3 prior lines of chemotherapy in the advanced/metastatic setting. Therapy given for only 1 cycle and discontinued because of toxicity in the absence of disease progression will not be counted as a line of therapy. Radio-sensitizing chemotherapy, if only given with radiation therapy will not be considered a line of therapy
-Patient must be willing to sign the relevant treatment cohort consent form
SCREENING PROTOCOL EXCLUSION CRITERIA:
-Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease. Patients with treated brain metastases are eligible if follow-up brain imaging 4 weeks after central nervous system-directed therapy shows no evidence of progression
-Patients requiring the use of full dose coumarin-derivative anticoagulants such as warfarin. Low molecular weight heparin is permitted for prophylactic or therapeutic use. Factor X inhibitors are permitted
Note: Warfarin may not be started while enrolled in the treatment cohorts. Stopping the anticoagulation for biopsy should be per site standard operating practice
ADDITIONAL EXCLUSION CRITERIA FOR TREATMENT COHORTS:
-Patients who are currently receiving any other investigational agent(s)
-Uncontrolled infection requiring intravenous antibiotic, antiviral, or antifungal use
-Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
