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| General |
| Study Status |
Study Pending |
Application Number /
Requirement Number |
P170019 S043/ PAS001 |
| Date Original Protocol Accepted |
12/01/2023
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| Date Current Protocol Accepted |
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| Study Name |
RET Fusion Clinical Efficacy PAS for Selpercatinib
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| Device Name |
FoundationOne CDx (F1CDx)
|
| General Study Protocol Parameters |
| Study Design |
Retrospective Cohort Study
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| Data Source |
Sponsor Registry
|
| Comparison Group |
No Control
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| Analysis Type |
Descriptive
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| Study Population |
Child: 2-12 yrs,
Adolescent: 13-18 yrs,
Transit. Adolescent A (distinctively) : 18-21 yrs,
Transit. Adolescent B (as adults) : 18-21 yrs,
Adult: >21
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| Detailed Study Protocol Parameters |
| Study Objectives |
The purpose and objective of the PAS will be to confirm the clinical effectiveness of F1CDx as a CDx device for identification of patients with
solid tumors with RET fusions, who may benefit from treatment with selpercatinib, by evaluating the objective response rate (ORR) for tissue
agnostic patients from the LIBRETTO-001 clinical trial.
The RET fusion-positive (i.e., clinical trial assay positive (CTA+)) samples from LIBRETTO-001 clinical trail will be used (i.e., patients enrolled under
tissue agnostic). The clinical registrational samples from the LIBRETTO-001 clinical trial have already been evaluated by the CTA for enrollment
purposes. The qualifying RET fusions are summarized in QSR-BPM-062: RET biomarker definition to support the selpercatinib CDx claim in the US,
European Union (EU), and Japan using F1CDx.
Approximately 29 TA patients enrolled in LIBRETTO-001 with available FFPE for F1CDx testing will be evaluated in this study (Table 6.1 below).
TA patients were enrolled in LIBRETTO-001 as RET fusion positive by a local test result (i.e. CTA+) and retrospectively tested by F1CDx. Among
the up to approximately 29 CTA+ TA patient samples, approximately 15 were previously tested under the clinical bridging study for the US (QSRVAL-
RPT-410-02, evaluated under P170019/S043), approximately six were previously tested under the clinical bridging study for Japan (QSR-VALRPT-
425-02), and an estimated eight will be available from patients who were enrolled into LIBRETTO-001 until a later enrollment cutoff date (Q1
2024) and will be tested by F1CDx for the purposes of the PAS.
Approximately eight unique FFPE tissue samples will be prospectively obtained from TA patients enrolled in the LIBRETTO-001 trial and
processed in this study. Final numbers will be provided in the study report. The ORR will be calculated using Response Evaluation Criteria in Solid
Tumors Version 1.1 (RECIST 1.1), consistent with the LIBRETTO-001 clinical study protocol. The ORR will be defined as the observed proportion
of patients whose best overall response is confirmed complete response (CR) or partial response (PR), as determined by an independent review
committee (IRC) and by the treating Investigator, and will be accompanied by a two-sided 95% confidence interval (CI) when applicable. The ORR
will be calculated using a clinical cutoff date (for clinical outcomes) planned for Q2 2025 for all approximately 29 CTA-positive TA patients
with a valid F1CDx test result (F1CDx evaluable). The ORR will be reported for the following groups:
CTA + TA patients that are RET fusion positive as determined by CTA.
F1CDx + CTA + TA patients that are RET fusion positive by both CTA and by F1CDx.
F1CDx - CTA + TA patients that are RET fusion positive by CTA but RET fusion negative by F1CDx.
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| Study Population |
RET fusion positive tissue agnostic patients Samples meeting the pre-defined criteria specified below will be included.
Inclusion Criteria
. FFPE tissue samples (blocks or slides)
. DNA derived from FFPE samples
. Samples obtained in accordance with QA-028, POL-01008, and IRB-approved protocols
. Samples obtained in accordance with IRB#:120160955, Use of Leftover Nucleic Acid Samples
that are Not Individually Identifiable for Analytical Validation Studies (FMI)
. Sample that meet minimum criteria for F1CDx testing operational requirements.
. Samples from the LIBRETTO-001 clinical trial with proper informed consent
Exclusion Criteria
. Samples failing to meet any of the inclusion criteria. LIBRETTO-001 clinical trial samples that lack clear identification or labeling
Samples not obtained in accordance with QA-028 and POL-01008 or not receiving IRB approval. Samples not obtained in accordance with IRB#:
120160955, Use of Leftover Nucleic Acid Samples that are Not Individually Identifiable for Analytical Validation Studies (FMI)
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| Sample Size |
A total of up to approximately 29 TA patients enrolled in LIBRETTO-001, with available FFPE for F1CDx testing, will be evaluated in this study. TA
patients were enrolled in LIBRETTO-001 as RET fusion positive by a local test result (i.e., CTA positive) and retrospectively tested by F1CDx. Among
the up to approximately 29 CTA-positive TA patient samples, ~15 will be from the clinical bridging study for the US, ~6 will be from the clinical
bridging study for Japan, and an estimated ~8 will be available from patients who were enrolled into LIBRETTO- 001 until a later enrollment
cutoff date (Q1 2024) and tested by F1CDx for the purposes of this post approval study.
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| Key Study Endpoints |
To evaluate the clinical effectiveness of selpercatinib for TA patients with RET fusions from LIBRETTO-001, the ORR will be calculated using
Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), which is consistent with that in the LIBRETTO-001 clinical study protocol.
The ORR will be defined as the observed proportion of patients whose best overall response is confirmed complete response (CR) or partial response
(PR) as determined by independent review committee (IRC) and by the treating Investigator and will be accompanied by a two-sided 95%
confidence interval (CI) when applicable. The ORR will be calculated using a clinical cutoff date (for clinical outcomes) planned for Q2 2025 for all
approximately 29 CTA-positive TA patients with a valid F1CDx test result (F1CDx evaluable). The ORR will be reported for the following groups:
CTA + TA patients that are RET fusion positive as determined by CTA.
F1CDx + CTA + TA patients that are RET fusion positive by both CTA and by F1CDx.
F1CDx - CTA + TA patients that are RET fusion positive by CTA but RET fusion negative by F1CDx.
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| Follow-up Visits and Length of Follow-up |
For safety follow up: 28 days (+7 days) after final dose of study drug.
For long-term follow up: approximately every 3 month (-/+ 1 month) after that last dose of study drug.
Long term follow up will occur until the patient has withdrawn consent for further participation, is lost to follow up, has died, or the Sponsor makes a
decision to close the study.
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