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U.S. Department of Health and Human Services

Post-Approval Studies (PAS) Database

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The FDA has the authority to require sponsors to perform a post-approval study (or studies) at the time of approval of a premarket approval (PMA), humanitarian device exemption (HDE), or product development protocol (PDP) application. Post-approval studies can provide patients, health care professionals, the device industry, the FDA and other stakeholders information on the continued safety and effectiveness (or continued probable benefit, in the case of an HDE) of approved medical devices. This database allows you to search Post-Approval Study information by applicant or device information.

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MK-3475 MSI-H FMI F1CDx Post Approval Analysis

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Study Status Study Pending
Application Number /
Requirement Number
P170019 S029/ PAS001
Date Original Protocol Accepted 04/13/2022
Date Current Protocol Accepted  
Study Name MK-3475 MSI-H FMI F1CDx Post Approval Analysis
Device Name FoundationOne CDx (F1CDx)
General Study Protocol Parameters
Study Design Retrospective Cohort Study
Data Source Sponsor Registry
Comparison Group Historical Control
Analysis Type Descriptive
Detailed Study Protocol Parameters
Study Objectives The purpose of this study is to confirm in a post marketing setting the clinical effectiveness of the F1CDx as a companion diagnostic in identifying MSI-H solid tumor patients for treatment with pembrolizumab. While the clinical validity of the F1CDx for this intended use has been established in the sPMA (P170019/S029) by demonstrating a clinically meaningful response to pembrolizumab in MSI-H solid tumor patients identified by the F1CDx (ORR: 43.0%, 95% CI: [33.5, 52.9]), the intent of the proposed study is to show that the response rate to treatment with pembrolizumab seen in the additional F1CDx-positive participants included in this analysis are qualitatively similar to the previously established (P170019/S029) response rate.
The primary objective of this study is to estimate the objective response rate (ORR) for pembrolizumab treatment among clinical study subjects whose archived solid tumor specimens are MSI-H as determined by retrospective testing with the F1CDx (CDx).
Primary analysis will be based on subjects with complete CDx status, and sensitivity analysis will include subjects with and without CDx results. The missing CDx results will be imputed in the sensitivity analysis. The imputation model obtained using the sPMA primary efficacy population (KN164 + KN158 cohort K post amendment 7) will be applied.
The key estimate of interest is the objective response rate (ORR): the proportion of subjects with best overall response being PR or CR among patients whose tumors are MSI-H by the CDx. Duration of response (DOR) will be reported as an additional endpoint.
Study Population This study consists of 41 additional participants from KN158 Cohort K that were not included in PMA Supplement P170019/S029. Cohort K in KN-158 is an ongoing multicenter, global, open-label, single-arm cohort of pembrolizumab in participants with any advanced MSI-H/dMMR solid tumor (except CRC) that was incurable and for which prior standard first-line treatment had failed. MSI/MMR status was determined locally for enrollment eligibility determination. As this is a single-arm trial, there is no control arm and participants were not randomized. KN158 Cohort K enrolled a total of 355 participants with MSI-H/dMMR tumors; enrollment is complete. The 41 participants included in the proposed study have been enrolled and treated with pembrolizumab.
Data from these participants was not included in the sPMA (P170019/S029) because they either did not have 26 weeks of follow-up (31 patients) by the data cut-off date of October 5, 2022 or samples (from 10 participants) were inadvertently not sent to FMI for MSI testing, despite being eligible for the efficacy population of the sPMA dataset. These 10 samples were subsequently sent to FMI for MSI testing.
Thus, the total number of participants with F1CDx MSI testing results that will be included in the proposed study is 41 (16 patients with endometrial cancer, 14 with gastric cancer, 1 with anal cancer, 2 with breast cancer, 2 with cervical cancer, 4 with glioma, 1 with ovarian cancer and one with small intestine cancer). Among the 41 participants whose samples were tested by the CDx, 21 had F1CDx-positive status (10 with endometrial cancer, and 11 with gastric cancer), 10 had F1CDx-negative status (1 with cervical cancer, 5 with endometrial cancer, 3 with glioma and 1 with small intestine) and 10 had non-evaluable CDx status due to failing CDx QC metrics. It is anticipated that the primary population for efficacy analysis will be the 21 CDx positive patients, supplemented by a missing data sensitivity analysis imputing CDx status in the 10 non-evaluable patients via application of the same imputation model built for the sPMA.
Sample Size A total of 41 patients (21 F1CDx-positive, 10 F1CDx-negative and 10 F1CDx-nonevaluable)
Key Study Endpoints Primary Endpoints:
Investigator-assessed Objective Response Rate (ORR)
The primary efficacy endpoint is Objective Response Rate (ORR) by RECIST v1.1 as assessed by the investigator.
Sensitivity Analysis
A sensitivity analysis based on multiple imputation of CDx status to incorporate clinical outcome data for the 10 nonevaluable participants will also be performed.
Secondary endpoints:
ORR will also be assessed in subjects with observed CDx-negative and CDx-non-evaluable status. DOR may be descriptively analyzed given that responder sample size is not large enough per each CDx status (CDx-positive, CDx-negative, and CDx-non-evaluable).
Follow-up Visits and Length of Follow-up 26 weeks

MK-3475 MSI-H FMI F1CDx Post Approval Analysis Reporting Schedule

Reporting Schedule
Date Due
FDA Receipt
Applicant's Reporting Status
progress report 05/18/2022 05/18/2022 On Time
6 month report 08/19/2022 11/09/2022 Overdue/Received
1 year report 02/18/2023    
18 month report 08/19/2023    
2 year report 02/18/2024    
3 year report 02/17/2025    

Contact Us

Mandated Studies Program
Food and Drug Administration
10903 New Hampshire Ave.
Silver Spring, MD 20993-0002
Email: MandatedStudiesPrograms@fda.hhs.gov

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