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.
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
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
Sequential
Biopsy Procedure
Procedure/SurgeryUndergo biopsy
Biospecimen Collection
Procedure/SurgeryUndergo collection of blood samples
Computed Tomography
Procedure/SurgeryUndergo CT
Echocardiography Test
Procedure/SurgeryUndergo ECHO
Electronic Health Record Review
Other interventionUndergo review of SOC RNA testing results
Enfortumab Vedotin
DrugGiven IV
Immunohistochemistry Staining Method
Other interventionUndergo IHC assay
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Multigated Acquisition Scan
Procedure/SurgeryUndergo MUGA
Sacituzumab Govitecan
Biological/VaccineGiven IV
Trastuzumab Deruxtecan
Biological/VaccineGiven IV
Frequency of high protein expression in patients with high ribonucleic acid (RNA) expression of each antibody-drug conjugate target (screening protocol)
Objective response rate (treatment cohorts)
Will be defined as the proportion of patients who achieve complete response or partial response per the Response Evaluation Criteria in Solid Tumors version 1.1. For each treatment cohort, 90% two-sided confidence intervals will be calculated for objective response rate.
Frequency that patients with high RNA and immunohistochemistry target expression receive cohort treatment on study (screening protocol)
Progression free survival (treatment cohorts)
Will be estimated using the Kaplan-Meier method. For each treatment cohort, 90% two-sided confidence intervals will be calculated for the proportion of patients alive and progression free at 6 months from start of cohort treatment.
Overall survival (treatment cohorts)
Will be estimated using the Kaplan-Meier method.
Time to progression (treatment cohorts)
Will be estimated using the Kaplan-Meier method.
Mechanisms of acquired resistance (treatment cohorts)
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