[90Y]Y-PTT Endoradiotherapy in CNS Lymphoma Patients

Inclusion Criteria:

Patients are eligible to be included in the study only if all of the following criteria apply and are maintained at Day -2 to Day 0 (before IMP infusion):

1. Signed informed consent, by the patient or an authorized legal guardian in case thepatient is temporarily not competent due to his or her disease, obtained before anystudy-related activities. Study-related activities are any procedures that arecarried out as part of the study, including activities to determine suitability forthe study.

2. Patients of either gender aged > 18 years.

3. Body weight < 180 kg.

4. At least one measurable lymphoma manifestation in the CNS, either contrast-enhancedlesion in the brain parenchyma or measurable meningeal lesion.

5. Histologically, cytologically or radiologically confirmed relapsed/refractoryprimary central nervous system lymphoma (PCNSL) or relapsed/refractory secondarycentral nervous system lymphoma (SCNSL). Initial histologic confirmation at firstdiagnosis is mandatory. No peripheral lymphoma evidence is allowed.

6. Recurrent or refractory CNSL

7. For recurrent disease, comprising new lesions or recurrent CNSL after acomplete response (CR) at that site, there are no maximum number ofrecurrences.

8. Refractory CNSL comprises patients with non-responding CNSL (no objectiveresponse rate (ORR), no progressive disease (PD)) to frontline therapy, orprogressive disease after an initial, partial response (PR).

9. Stored stem cells with at least ≥ 2 x 106 CD34+ cells/kg of body weight.

10. If sexually active female patient of childbearing potential: patient agrees to takeadequate contraceptive measures during study participation and agrees to continueuse of this method for the duration of the study and for six months after the lastdose.

11. Female patient without childbearing potential: documented history (e.g., tuballigation or hysterectomy) or is post-menopausal.

12. For male patient whose partner is of child-bearing potential: patient is willing toensure that he and his partner use effective contraception during the study and forsix months after 90Y-PTT treatment.

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

14. Confirmed presence of CXCR4 on technically evaluable tumor lesions documented by avisually CXCR4-positive [68Ga]Ga-PentixaFor positron emission tomography (PET) scanwithin two months prior to enrolment in the study or during Screening.

15. Blood test results as follows:

16. Absolute neutrophil count: > 1.0 x 109/L

17. Hemoglobin: ≥ 8 g/dL

18. Platelets: ≥ 75 x 109/L

19. Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkalinephosphatase (ALP): ≤ 3 x ULN (upper limit of normal)

20. Serum creatinine: ≤ 2 x ULN and Cockcroft Gault calculated glomerularfiltration rate (GFR) ≥ 50 mL/min

21. Bilirubin: ≤ 3 x ULN

Exclusion Criteria:

Patients are excluded from the study if any of the following criteria apply during screening or Day -2 to Day 0 (before IMP infusion):

1. Known or suspected hypersensitivity to study product(s) or related products.

2. Contraindication for contrast-enhanced magnetic resonance imaging (MRI) as set outin the relevant institutional guidelines (e.g., pacemaker, defibrillator, aneurysmclip, metal in the body, renal insufficiency, severe claustrophobia etc.) orcontraindication for the use of gadolinium contrast for MRI.

3. Previous participation in this study. Participation is defined as signed informedconsent.

4. Female who is pregnant, breast-feeding or intends to become pregnant or is ofchild-bearing potential and not using an adequate contraceptive method (adequatecontraceptive measures as required by local regulation or practice). A pregnancytest will be performed at the start of the study for all female patients ofchildbearing potential (i.e., not surgically sterile or two years postmenopausal).

5. Male of reproductive age who or whose partner(s) is not using an adequatecontraceptive method (adequate contraceptive measures as required by localregulation or practice).

6. Participation in any clinical study of an approved or non-approved investigationalmedicinal product (IMP) within the last 30 days (or ≤ 5 terminal eliminationhalf-lives of previous IMP, whichever is longer) before screening.

7. Any disorder (e.g., active infection, unstable angina pectoris, cardiac arrhythmia (excluding atrial fibrillation and atrial flutter, uncontrolled congestive heartfailure), poorly controlled hypertension, poorly controlled diabetes mellitus [HbA1c ≥ 9%], etc.) or laboratory findings, except for conditions associated with CNSlymphoma, which in the investigator's opinion might jeopardize patient's safety orcompliance with the protocol.

8. Presence of active infection, or history of serious infection six weeks prior to IMPadministration. Patients with uncontrolled human immunodeficiency virus (HIV)infection as well as acute or chronic active hepatitis B virus (HBV) or hepatitis Cvirus (HCV) infection are excluded (Note: Patients on antiretroviral therapy (ART)with controlled HIV infection (defined as sufficient ART compliance, non-measurableHIV and CD4+ T helper cells > 200/Micro Liter) may be enrolled, if consideredeligible for study treatment by the investigator.).

9. SCNSL with systemic involvement.

10. Chronic use (> 21 days) of immunosuppressive drugs, e.g., steroids for systemicautoimmune disease, due to previous organ transplantation, or other clinicallyevident form of immunodeficiency. Patients receiving only acute treatment (less than 21 days) with corticosteroids can be included.

11. Any mental condition rendering the patient unable to understand the nature, scope,and possible consequences of the study, and/or evidence of an uncooperative attitudewithout designated legal representative.

12. Brain radiation therapy ≤ 180 days before IMP infusion.