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)

Conditions

• Advanced Malignant Solid Neoplasm
• Metastatic Malignant Solid Neoplasm

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Biopsy Procedure — PROCEDURE
  Undergo biopsy
• Biospecimen Collection — PROCEDURE
  Undergo collection of blood samples
• Computed Tomography — PROCEDURE
  Undergo CT
• Echocardiography Test — PROCEDURE
  Undergo ECHO
• Electronic Health Record Review — OTHER
  Undergo review of SOC RNA testing results
• Enfortumab Vedotin — DRUG
  Given IV
• Immunohistochemistry Staining Method — OTHER
  Undergo IHC assay
• Magnetic Resonance Imaging — PROCEDURE
  Undergo MRI
• Multigated Acquisition Scan — PROCEDURE
  Undergo MUGA
• Sacituzumab Govitecan — BIOLOGICAL
  Given IV
• Trastuzumab Deruxtecan — BIOLOGICAL
  Given IV

Study Details

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.

Key Dates

Start date

Mar 18, 2025

Status verified

Mar 2026

Primary completion

Mar 31, 2028

Completion

Mar 31, 2028

Study Design

Enrollment

500 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: Cohort A (sacituzumab govitecan)
  Patients receive sacituzumab govitecan-hizy IV over 1-3 hours on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI throughout the trial, undergo biopsy after enrollment to cohort but prior to treatment and again on study, and undergo collection of blood samples after enrollment to cohort but prior to treatment. Patients may optionally undergo biopsy at the time of progression and may optionally undergo collection of blood samples on study and at the time of progression.
• Experimental: Cohort B (enfortumab vedotin)
  Patients receive enfortumab vedotin IV over 30 minutes on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI throughout the trial, undergo biopsy after enrollment to cohort but prior to treatment and again on study, and undergo collection of blood samples after enrollment to cohort but prior to treatment. Patients may optionally undergo biopsy at the time of progression and may optionally undergo collection of blood samples on study and at the time of progression.
• Experimental: Cohort C (trastuzumab deruxtecan)
  Patients receive trastuzumab deruxtecan IV over 90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI throughout the trial, undergo biopsy after enrollment to cohort but prior to treatment and again on study, and undergo collection of blood samples after enrollment to cohort but prior to treatment. Patients also undergo ECHO or MUGA at screening and on study. Patients may optionally undergo biopsy at the time of progression and may optionally undergo collection of blood samples on study and at the time of progression.
• Other: Screening (record review, IHC assay)
  SCREENING STEP 1: Patients who have previously undergone SOC RNA testing have the results of their SOC RNA testing reviewed. Patients whose tumor expresses an appropriate TOI by RNA testing proceed to screening step 2. SCREENING STEP 2: Patients have TOI expression testing at the protein level by IHC assay performed on previously collected tissue. Patients with high Trop-2 protein expression are assigned to Cohort A. Patients with high nectin-4 protein expression are assigned to Cohort B. Patients with high HER2 protein expression are assigned to cohort C.

Primary Outcome Measure

Frequency of high protein expression in patients with high ribonucleic acid (RNA) expression of each antibody-drug conjugate target (screening protocol) [ Time Frame: Up to completion of screening period ]

Locations (27)

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