Ignite Creation Date:
2024-05-06 @ 8:16 PM
Last Modification Date:
2024-10-26 @ 3:23 PM
Study NCT ID:
NCT06311214
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-06-05
First Post:
2024-03-13
Brief Title:
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
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
Optimizing Antibody-Drug Conjugate Therapy Through Molecular Analysis for Therapy Choice ADC MATCH
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 persons 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
Detailed 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 response profile of patients with advancedmetastatic 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 advancedmetastatic 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 PFS2PFS1 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 RNAprotein 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 andor 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 andor 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 andor 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
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 response profile of patients with advancedmetastatic 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 advancedmetastatic 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 PFS2PFS1 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 RNAprotein 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 andor 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 andor 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 andor 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| UM1CA186688 | NIH | CTEP | httpsreporternihgovquickSearchUM1CA186688 |
| NCI-2024-01903 | REGISTRY | None | None |
| 10397 | OTHER | None | None |
| 10397 | OTHER | None | None |