RecruitingAdvanced Malignant Solid NeoplasmMetastatic Malignant Solid Neoplasm

Personalized Antibody-Drug Conjugate Therapy Based on RNA and Protein Testing for the Treatment of Advanced or Metastatic Solid Tumors (The ADC MATCH Screening and Treatment Trial)

Eligible age

18+ yrs

Accepts

All genders

Locations

15 states

Healthy volunteers

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About this study

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.

Sponsor: National Cancer Institute (NCI)

You may qualify if…

✓ 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
✓ Patient must have undergone RNA testing in a Clinical Laboratory Improvement Act (CLIA) environment or must submit archival tissue to determine RNA overexpression of ADC TOIs by the TARGET Assay. Patients who have high TOI RNA expression will have confirmation of TOI expression by CLIA IHC assay at MD Anderson Cancer Center (MDACC). Only patients with confirmed TOI protein expression will be eligible for assignment to a treatment cohort. Retrospective confirmation in another central laboratory may also be performed. (A proportion of specimens in patients who are negative for RNA overexpression may be tested to better understand the concordance between the TARGET Assay and immunohistochemistry (IHC) assays, as funding and tissue availability allows. Only patients with RNA and protein expression with be eligible for treatment on ADC MATCH)

You may not qualify if…

✕ 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
✕ Clinically significant cardiovascular condition including: (1) history of congestive heart failure (New York Health Association class \> 2), (2) any history of unstable angina, (3) myocardial infraction within the past 12 months, or (4) any history of supraventricular arrhythmia or ventricular arrhythmia requiring treatment or intervention within the past 12 months
✕ History or presence of abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful
✕ Active or chronic corneal disorder including, but not limited to, Sjogren's syndrome, Fuchs corneal dystrophy (requiring treatment), history of corneal transplantation, active herpetic keratitis, and/or active ocular conditions requiring ongoing treatment/monitoring such as wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, presence of papilledema, and acquired monocular vision
✕ History of allergic reactions attributed to compounds of similar chemical or biologic composition to the ADCs used in the study
✕ History of interstitial lung disease or pneumonitis requiring steroid therapy
✕ Grade 2 or greater peripheral neuropathy