Study BX43361 is a global, interventional, multicenter, master biomarker screening study. The overarching structure of this study is a flexible master screening process that will test patients’ tumor tissue to determine biomarker status using a central laboratory. Tumor tissue from eligible patients will be submitted for centralized, indication-appropriate biomarker testing, as needed for linked trials.
The results of this testing will be used to identify patients with an appropriate biomarker profile, for potential participation in a linked Roche clinical trial.…
This master screening study will be conducted initially only to identify biomarker eligible patients with either locally advanced, unresectable Stage III NSCLC or Stage II, IIIA, or select IIIB (T3N2 only) NSCLC requiring adjuvant treatment (see Appendix 2).
However, it is anticipated that Study BX43361 will be amended in the future to include additional linked Roche clinical trials.

• No therapeutic intervention will be administered to patients in this screening
  study.

• No therapeutic intervention will be administered to patients in this screening study.…

• …

Patients must meet the following criteria for study entry:
 Signed Informed Consent Form
 Age  18 years at time of signing Informed Consent Form
 Given that the aim of Study BX43361 is to assign patients to a biomarker-appropriate linked Roche clinical trial
– Awareness of and willingness, in principle, to participate in an assigned cohort of a linked Roche clinical trial
– Ability to comply with future investigational treatment protocol procedures in the investigator’s judgment and based on discussion with the patient, for example, dosing of medication (e.g., oral or IV), tumor assessments, safety monitoring, agreement to meet contraceptive requirements, and completion of questionnaires
 Confirmed availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumor specimen that meets the criteria outlined in protocol
A representative FFPE block (preferred) or 1520 slides containing unstained, freshly cut, serial tumor tissue sections (45 m thick) must be submitted at study enrollment (i.e., Day 1). At the discretion of the investigator, if fewer than 15 slides are available, but the available tissue meets the sample type and quality required in Section 4.4.4 protocol, the patient may still be eligible for the study.
In such instances, the evaluation of the available tissue should be documented in the patient’s notes and the Sponsor informed.
Please refer to Section 4.4.4 protocol for specific sample requirements.
 Adequate hematologic and end-organ function by the investigator’s clinical judgement, including the following:
– No clinically significant hematologic (CBC), coagulation, or biochemistry test results
– No indications and/or known history of clinically significant acute or chronic liver, or kidney injury
Stage-Specific Inclusion Criteria
All patients are required to meet, or expected to meet, within a reasonable period, (see Section 4.1) one of the following staging-specific criteria in Sections 4.1.2.2 or 4.1.2.1, and the sites will be able to provide access for biomarker-eligible patients to an appropriate linked Roche clinical trial for that stage of disease.
To ensure the best patient outcomes, sites are strongly encouraged to identify patients who may be potentially eligible for enrollment in a treatment study or cohort as early in the patient’s treatment pathway as possible.
Patients with Stage III NSCLC
Patients with Stage III NSCLC must meet the following criteria for study entry:
 Locally advanced, unresectable Stage III NSCLC of either squamous or non-squamous histology based on 8th edition of the American Joint Committee on Cancer (AJCC) and Union for International Cancer Control (UICC) cancer staging system (Amin et al. 2017), with plans to receive, currently receiving, or received chemoradiation treatment
 Representative FFPE tumor specimen (meeting requirements in Section 4.4.4 in protocol )
obtained prior to the start of any chemoradiotherapy
Screening within Study BX43361, using a pretreatment biopsy, is encouraged to be performed as early in the patient treatment pathway as possible, and may occur before starting, during, or after chemoradiation treatment provided the timelines detailed below are met.
Patients may be enrolled in the study and tissue can be submitted for biomarker testing, while still receiving concurrent chemoradiotherapy (cCRT) or sequential chemoradiotherapy (sCRT) for consideration of enrollment in consolidation
treatment studies.
For patients who enter Study BX43361 after completion of cCRT or sCRT, the tumor specimen should be sent for biomarker testing (on Day 1) within 10 days after the final dose of cCRT or sCRT. Randomization into a linked Roche clinical trial must occur within 42 days after the final dose of cCRT or sCRT.
Patients must not have received or under consideration for consolidation chemotherapy after cCRT or sCRT.
 Eastern Cooperative Oncology Group (ECOG) Group Performance Status of 0, 1, or 2
Patients with Stage II, IIIA, or Select IIIB (T3N2 only) NSCLC Requiring Adjuvant Treatment
Patients with Stage II to IIIB NSCLC must meet the following criteria for study entry:
 Stage II, IIIA, or select IIIB (T3N2 only) NSCLC based on the 8th edition of the AJCC and UICC cancer staging system (Amin et al. 2017)
 Considered eligible for curative intent surgery (complete resection with all surgical margins testing negative for tumor).
Accepted types of resection include any of the following: lobectomy, sleeve lobectomy, bilobectomy, or pneumonectomy.
Resection by segmentectomy or wedge resection is not allowed.
 Screening within Study BX43361, using a pretreatment biopsy, is encouraged to be performed as early in the patient treatment pathway as possible to ensure the patient is potentially eligible for all cohorts, and should meet the following guidelines:
– For patients enrolled prior to surgery:
There must be sufficient tumor biopsy tissue (representative FFPE tumor specimen, meeting requirements in Section 4.4.4) available for evaluation prior to the start of any anti-cancer treatment (if receiving neoadjuvant therapy).
– For patients enrolled following surgery:
The screening study should be considered an appropriate option per investigator, given that biomarker testing results will be available after surgery and therefore, patients would only be eligible for cohorts testing adjuvant treatment and not peri-operative cohorts.
These patients should achieve complete resection of histologically
confirmed Stage II, IIIA, or select IIIB (T3N2 only) with all surgical margins testing negative for tumor.
It is strongly recommended that patients should be enrolled no more than 8 weeks after surgery, and prior to post-operative chemotherapy (as applicable). Investigators should make reference to the relevant linked Roche clinical trial protocol to ensure sufficient time is given to
subsequently screen the patient within the linked trial for biomarker-eligible patients identified.
 Representative FFPE tumor specimen (meeting requirements in Section 4.4.4 in protocol)
obtained prior to the start of any treatment
 ECOG Performance Status of 0 or 1

General Exclusion Criteria
Patients who meet any of the following criteria will be excluded from study entry:
 Pregnant or breastfeeding, or intending to become pregnant during the study
Women of childbearing potential who are required (and have consented) to have a study-mandated procedure for which pregnancy would impact the risks to the patient and/or fetus per local guidelines must have a negative serum pregnancy test result within 7 days prior to the procedure.
 History of malignancy other than NSCLC within 5 years prior to screening, except for malignancies with a negligible risk of metastasis or death (e.g., 5-year overall survival rate  90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal breast carcinoma in situ, or Stage I uterine cancer
 Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications. This includes any of the following:
– Known clinically significant liver disease (e.g., active viral, alcoholic, or other hepatitis; cirrhosis; current alcohol abuse)
– Significant cardiovascular disease (e.g., New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to enrollment (i.e., Day 1 of the study when tissue is sent to the central laboratory), unstable arrhythmia, or unstable angina
– Recent major surgical procedure or anticipation of a need for a major surgical procedure, except for patients who have recently had and have adequate healing after complete surgical resection of tumor
– Prior allogeneic stem-cell or solid-organ transplantation
– Recent or ongoing severe or clinically significant infection, including but not limited to, hospitalization for complications of infection, bacteremia, or severe

• pneumonia……