Study of Safety and Efficacy of Betalutin and Rituximab in Patients With FL

Inclusion criteria

• Patient must be ≥18 years at the time of signing the informed consent
• ECOG performance status of 0-2
• Histologically confirmed diagnosis (by 2008 World Health Organization [WHO] classification) of follicular lymphoma (grade 1, 2 or 3a)
• At least one (but not more than 3) prior regimens with an anti-CD20 antibody (alone or in combination with chemotherapy), with documented relapsed, refractory disease (must not be anti-CD20 antibody-refractory) or PD
• Presence of at least one bi-dimensionally measurable lesion by CT or MRI: longest diameter (LDi) >1.5 cm for a nodal lesion; LDi >1.0 cm for an extranodal lesion within 28 days prior to start of treatment
• Normal organ and bone marrow function defined as:

• Absolute neutrophil count ≥1.5 x 109/L;
• Platelet count ≥150 x 109/L;
• Haemoglobin ≥9 g/dL;
• Total bilirubin ≤1.5 x upper limit of normal (ULN) (except patients with documented Gilbert's syndrome [<3.0 mg/dL]);
• Aspartate transaminase (AST); Alanine transaminase (ALT) or Alkaline phosphatase (ALP) ≤2.5 x ULN (or ≤5.0 x ULN if liver involvement by primary disease);
• Adequate renal function as demonstrated by a serum creatinine within the upper limit of normal range
• Bone marrow involvement by lymphoma <25%
• Life expectancy >3 months
• Negative hepatitis B, hepatitis C and human immunodeficiency virus (HIV) screening tests
• Patients must agree to use effective contraception for 12 months following last study drug administration

Exclusion criteria

• Previous haematopoietic stem cell transplantation (autologous and allogenic)
• Evidence of histological transformation from FL to DLBCL at time of screening.
• Previous total body irradiation
• Chemotherapy, immunotherapy or investigational therapy within 28 days before the start of study drug administration (corticosteroid treatment at doses of ≤20 mg/day, topical or inhaled corticosteroids, granulocyte colony-stimulating factor [G-CSF] or granulocyte-macrophage colony-stimulating factor [GM CSF] are permitted up to 2 weeks prior to start of study treatment) or failure to recover from AEs associated with prior treatment
• Previous treatment with radioimmunotherapy
• Patients who are receiving any other investigational medicinal products
• Known or suspected central nervous system (CNS) involvement of lymphoma
• History of a previous treated cancer except for the following:

• adequately treated local basal cell or squamous cell carcinoma of the skin
• cervical carcinoma in situ
• superficial bladder cancer or localised prostate cancer undergoing surveillance or surgery
• localised breast cancer treated with surgery and radiotherapy but not including systemic chemotherapy
• other adequately treated Stage 1 or 2 cancer currently in CR
• Pregnant or lactating women
• Exposure to another CD37 targeting drug
• A known hypersensitivity to RTX, lilotomab, Betalutin or murine proteins or any excipient used in RTX, lilotomab or Betalutin
• Receipt of live, attenuated vaccine within 30 days prior to enrolment
• Evidence of severe or uncontrolled systemic diseases (e.g. ongoing infection, respiratory, cardiac, hepatic or psychiatric conditions) which in the Investigator's opinion would compromise the protocol objectives