A Phase 1/2 Study of Lutetium (177Lu)-Lilotomab Satetraxetan (Betalutin®) Antibody-radionuclide-conjugate for Treatment of Relapsed Non-Hodgkin Lymphoma.

• Histologically confirmed (by World Health Organization \[WHO\] classification) relapsed incurable non-Hodgkin B-cell lymphoma of following subtypes; follicular grade I-IIIA (for Part C, this excludes patients meeting Part B criteria, who should enter Part B), marginal zone, small lymphocytic, lymphoplasmacytic, mantle cell.

• Age ≥ 18 years.

• Part A: A pre-study WHO performance status of 0-1; Part C: WHO performance status of 0-2.

• Life expectancy should be ≥3 months.

• \<25% tumour cells in bone marrow biopsy (biopsy taken from a site not previously irradiated).

• Measurable disease by radiological methods.

• Women of childbearing potential must:

∙ understand that the study medication is expected to have teratogenic risk.

‣ have a negative pregnancy test.

‣ agree to use, and be able to comply with, effective contraception without interruption, 4 weeks before starting study medication, throughout study medication therapy and for 12 months after end of study medication therapy, even if she has amenorrhoea.

• Male patients must agree to use condoms during intercourse throughout study medication therapy and the following 12 months.

• Patients previously treated with native rituximab are eligible.

⁃ The patient is willing and able to comply with the protocol, and agrees to return to the hospital for follow up visits and examination.

⁃ The patient has been fully informed about the study and has signed the informed consent form.

• Histologically confirmed (by WHO classification) relapsed non-Hodgkin B-cell FL (grade I IIIA).

∙ Male or female aged ≥18 years. 3. Received at least 2 prior systemic anti-neoplastic or immunotherapy-based regimens (maintenance therapy following a CR/PR is not considered to be a separate line of therapy). Systemic regimens including agents such as idelalisib or other PI3K inhibitors qualify as a prior line of therapy.

∙ Prior therapy must have included a rituximab/anti-CD20 agent and an alkylating agent - which may be been administered in separate regimens.

∙ Patients must be refractory to any at least one previous regimen that contained rituximab or an anti CD20 agent, with refractoriness defined as:

• i. no response (no CR or PR) during therapy, or ii. a response (CR/PR) lasting less than 6 months after the completion of a regimen including rituximab/anti-CD20 therapy (including occurrence of progressive disease (PD) during rituximab/anti-CD20 maintenance therapy, or within 6 months of completion of maintenance therapy).

• WHO performance status of 0-2. 7. Life expectancy of ≥3 months. 8. Bone marrow tumour infiltration \<25% (in biopsy taken from a site not previously irradiated).

• Measurable disease by CT or MRI: longest diameter (LDi) \>1.5 cm for nodal lesion, LDi \>1.0 cm for extra nodal lesion on an assessment performed during the screening period.

• Criteria 10 and 11 must be satisfied within 72 hours of the administration of rituximab:

⁃ ANC ≥1.5×109/L. 11. Platelet count ≥100×109/L.

• Criteria 12 to 15 must be verified at time of eligibility review within 2 weeks prior to rituximab administration:

⁃ Haemoglobin ≥9.0 g/dL. 13. Total bilirubin ≤1.5×upper limit of normal (ULN) (except patients with documented Gilbert's syndrome \[\<3.0 mg/dL\]).

⁃ Liver enzymes: AST; ALT or ALP ≤2.5×ULN (or ≤5.0×ULN with liver involvement by primary disease).

⁃ Adequate renal function as demonstrated by a serum creatinine \<1.5×ULN. 16. Women of childbearing potential must:

• understand that the study medication is expected to have teratogenic risk.

• have a negative serum beta human-chorionic gonadotropin (ß-HCG) pregnancy test at screening.

• commit to continued abstinence from heterosexual intercourse (excluding periodic abstinence or the withdrawal method) or begin a highly effective method of birth control with a Pearl-Index \<1%, without interruption, from 4 weeks before starting study medication, throughout study medication therapy and for 12 months after end of study medication therapy, even if she has amenorrhoea. Apart from abstinence, highly effective methods of birth control are: i. Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal).

• ii. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) iii. Intrauterine device (IUD). iv. Intrauterine hormone-releasing system (IUS). v. Bilateral tubal occlusion. vi. Vasectomised partner. 17. Male patients must agree to use condoms during intercourse throughout study treatment administration and for 12 months following administration of Betalutin.

⁃ The patient is willing and able to comply with the protocol, and agrees to return to the hospital for follow up visits and examination.

⁃ The patient has been fully informed about the study and has signed the informed consent form.

⁃ Negative HAMA test at screening. 21. Negative test at screening for Hepatitis B (negative HBsAg and anti-HBc), Hepatitis C and HIV.