NY-ESO expression testing using Ventana*s IHC test in Daiichi Sankyo*s First-in-human study of DS-2243a in participants with Advanced Solid Tumors

This clinical performance study plan (CPSP) for Clinical Performance Study
CPS-01-DS2243-054 relates to the use of the NY-ESO (SP511) Clinical Trial Assay
(CTA) to identify and select New York esophageal squamous cell carcinoma -1
(NY-ESO-1) and L antigen family member 1 (LAGE-1) proteins (hereafter referred
to as NY-ESO) positive synovial sarcoma (SS), myxoid/round cell liposarcoma
(MRCLS), squamous cell type Non-small cell lung cancer (Sq-NSCLC),
Adenocarcinoma type Non-small cell lung cancer (Ad-NSCLC), or urothelial
carcinoma (UC) patients by light microscopy for recruitment into Daiichi
Sankyo*s drug study DS2243-054. This CPSP is compliant with ICH-GCP,
Declaration of Helsinki, GDPR and ISO20916 and contains references to the
requirements of a CPSP per Annex XIII, section 2.3.2 of EU Regulation 2017/746
on in vitro Diagnostic Medical Devices (IVDR) and the corresponding section of
supporting documents where the information is located.

As a primary objective, the performance of NY-ESO (SP511) CTA will be assessed
by determining how often the device is able to yield a valid NY-ESO positive
result. The corresponding endpoint for this study is the percentage of cases
that yield >= 1% viable tumor cells with positive cytonuclear staining, at any
intensity of staining.

Exploratory objective (related to NY-ESO expression of drug trial DS2243-054):
NY-ESO expression as determined by the NY-ESO (SP511) CTA and its correlation
with response and/ or safety of participants treated with DS-2243a will be
investigated.

This clinical performance study CPS-01-DS2243-054 will be conducted as a
combined investigation with Daiichi Sankyo*s corresponding drug study
DS2243-054 *PHASE 1, OPEN-LABEL, MULTICENTER, FIRST-IN-HUMAN TRIAL OF DS-2243a
IN PARTICIPANTS WITH ADVANCED SOLID TUMORS.*

Drug Trial DS2243-054
The First-in-Human trial, DS2243-054, is designed to evaluate the safety and
tolerability of DS-2243a and to provide a preliminary assessment of its
efficacy in the specified participant populations, that include participants
with advanced or metastatic SS, MRCLS, Sq-NSCLC, Ad-NSCLC, and UC.
This trial consists of two parts: Dose Escalation (Part 1) and Dose Expansion
(Part 2).

Dose Escalation Part (Part 1)
Dose escalation of DS-2243a to determine the maximum tolerated dose (MTD)
and/or the Recommended Dose for Expansion (RDE) of DS-2243a when administered
as a single agent in participants with SS, MRCLS, NSCLC (Sq/Ad), or UC.
SS and MRCLS will be enrolled in dose escalation and backfill selected by
HLA-A2 positivity, while NSCLC and UC can be enrolled only in backfill selected
by both HLA-A2 positivity and NY-ESO positivity.

Dose Expansion Part (Part 2)
Following the identification of the MTD (and/or RDE) and step-up dose regimen,
tumor specific dose-expansion cohorts (Part 2) will be initiated in the
following indications: SS (and/or MRCLS), sq-NSCLC, UC, and Ad-NSCLC.
Additional participants may be enrolled based on the safety, efficacy,
biomarker, and PK data observed in Part 1 and Part 2.

Clinical performance Study CPS-01-DS2243-054
The Clinical Performance Study comprises the determination of NY-ESO expression
status using the NY-ESO (SP511) CTA for the purpose of eligibility assessments
for study DS-2243-054.
It does not include NY-ESO expression testing for exploratory purposes of study
DS2243-054.

Determination of the NY-ESO expression status in tumor tissue using the
investigational NY-ESO (SP511) CTA will be done as part of the screening
assessments. For specific cohorts, only patients with a positive test result
will be selected for drug trial DS2243-054.

False-Negative Results
A false-negative IHC test result i.e. an NY-ESO positive tumor with a test
result showing negative status at the protein/staining level, may result in
exclusion from the clinical trial where the study participant may opt for other
experimental therapies or clinical trials.
False-Positive Results
False positive results may result in patient inappropriately enrolled in the
clinical trial. Analytical validation and assay controls (positive and negative
system level controls) applied during centralized testing will minimize the
risk of false positive and false negative results. Residual risks to study
subjects will be mitigated by measures related to the experimental treatment,
including monitoring for cytokine release syndrome (CRS) and CRS-induced
cytopenia. Furthermore, DS-2243a will be administered subcutaneously, and a
suitable step-up dose regimen will be implemented to reduce CRS risk. The risk
is also considered to be acceptable since these patients should have received
prior standard of care (SoC) therapies and this clinical trial is considered by
the investigator to have a better risk/benefit assessment than the alternative
therapies available.

Clinical Benefit Assessment
The clinical utility and/or benefit of the NY-ESO (SP511) CTA has not been
established. This CTA will be used to identify and select NY-ESO positive
advanced solid tumor patients for recruitment onto drug study DS2243-054.

Overall Benefit-Risk Assessment
It is not expected that the results from the investigational CTA would expose
study subjects to excess risk. Planned study will enroll patients who are
deemed appropriate for an investigational treatment in the opinion of the
investigator and fulfill the eligibility criteria detailed in the clinical
study protocol. It is expected that these patients will have no standard
treatment options which are known to be effective.
Based on the safety data generated in the nonclinical studies, and considering
the planned risk mitigation strategies, the anticipated benefit risk profile of
the DS-2243a is considered to be favourable and justifies the clinical
development advancement