A Brain Metastases Research Platform to Tackle the Challenge of CNS Metastases in Solid Tumours

Inclusion Criteria:

1. Age ≥ 18 years old

2. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

3. Female or Male

4. Eligible for part A: Subjects (from cohorts 1 to 5) with newly diagnosed or up to 24months from diagnosis of non-CNS metastases. Enrolment of exceptional casessurpassing 24 months from diagnosis will be allowed for up to 20% of subjectsenrolled with HER2+ BC (cohort 2) and NSCLC harbouring driver mutations (cohort 3). Eligible for part B: Subjects (from cohorts 1 to 7) presenting with a first CNSevent and not yet enrolled in the program Seven cohorts of subjects are defined in this prospective multicenter study:

• Cohort 1: Triple negative breast cancer (TNBC)

• Cohort 2: HER 2 positive breast cancer (HER2+ BC)

• Cohort 3: Non-small cell lung cancer (NSCLC)

• Cohort 4: Small cell lung cancer (SCLC)

• Cohort 5: Melanoma

• Cohort 6: Other solid tumours (apart from the above mentioned subtypes

• Cohort 7: Radiologically or cytologically confirmed leptomeningealcarcinomatosis

5. Availability of either primary and/or non-CNS metastatic archival tumour tissue ismandatory for inclusion.

6. Willingness to undergo lumbar puncture at diagnosis of CNS metastases unless medicalcontra-indications

7. Predicted life expectancy > 3 months.

8. Women of childbearing potential must have a negative urine pregnancy test donewithin 28 days prior to enrolment

9. Effective contraception is in place for women of childbearing potential

10. Completion of all necessary screening procedures within 28 days prior to enrolment.

11. Signed Informed Consent form (ICF) obtained prior to any study related procedure. Inclusion criterion applicable to FRANCE only

12. Affiliated to the French Social Security System

Exclusion Criteria:

1. Pregnant and/or lactating women.

2. Previous or current malignancies of other histologies within the last 2 years, withthe exception of in situ carcinoma of the cervix, and adequately treated basal cellor squamous cell carcinoma of the skin.

3. Subject with a significant medical, neuro-psychiatric, or surgical condition,currently uncontrolled by treatment, which, in the principal investigator's opinion,may interfere with completion of the study. Exclusion criterion applicable to FRANCE only

4. Vulnerable persons according to the article L.1121-6 of the Public Health Code,adults who are the subject of a measure of legal protection or unable to expresstheir consent according to article L.1121-8 of the Public Health Code.