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)

Description

PRIMARY OBJECTIVES:

I. To evaluate the proportion of patients with expression of targets of interest (TOIs) by ribonucleic acid (RNA) testing who have expression of the TOI protein by immunohistochemistry (IHC). (ADC MATCH screening protocol) II. To evaluate the objective response rate (ORR) of patients with advanced/metastatic solid tumors and high TOI protein expression to matched ADCs. (ADC MATCH treatment cohorts)

SECONDARY OBJECTIVES:

I. To determine the proportion of patients with high validated TOI protein expression who receive treatment on ADC MATCH. (ADC MATCH screening protocol) II. To evaluate the proportion of patients with advanced/metastatic solid tumors who are alive and progression free at 6 months of treatment with targeted ADC. (ADC MATCH treatment cohorts) III. To evaluate time until death or disease progression. (ADC MATCH treatment cohorts) IV. To determine progression-free survival (PFS) compared to prior line of therapy (PFS2/PFS1). (ADC MATCH treatment cohorts) V. To determine the correlation of RNA and protein expression of TOIs. (ADC MATCH treatment cohorts) VI. To determine temporal tumor heterogeneity by comparing RNA/protein expression of TOIs on archival samples versus fresh biopsies. (ADC MATCH treatment cohorts) VII. To identify potential predictive biomarkers, including target expression (RNA and protein) and other molecular features (deoxyribonucleic acid [DNA], RNA, protein, immune markers). (ADC MATCH treatment cohorts) VIII. To determine pharmacodynamic changes in the tumor and microenvironment. (ADC MATCH treatment cohorts)

EXPLORATORY OBJECTIVE:

I. To determine mechanisms of acquired resistance. (ADC MATCH treatment cohort)

OUTLINE:

SCREENING STEP 1: Patients who have previously undergone standard of care (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.

COHORT A: Patients receive sacituzumab govitecan intravenously (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 computed tomography (CT) and/or magnetic resonance imaging (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.

COHORT B: 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.

COHORT C: 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 echocardiography (ECHO) or multigated acquisition scan (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.

At the time that a confirmed objective response is observed for a specific tumor type in any cohort, that tumor type may be expanded into a separate tumor-specific expansion cohort, with up to 2 expansion cohorts allowed per treatment cohort. At the time of disease progression, patients with expression of additional TOIs may be re-screened and assigned to receive treatment in up to 2 of the other treatment cohorts.

After completion of study treatment, patients are followed up at 30 days then every 3 months in years 1-2 and every 6 months in year 3.