A Prospective Multicenter Phase 2 Study of the Chemotherapy-Free Combination of the Intravenous Phosphatidylinositol-3-Kinase (PI3K) Inhibitor Copanlisib in Combination With Obinutuzumab in Patients With Previously Untreated Follicular Lymphoma (FL) and a High Tumor Burden

Inclusion Criteria: * Subjects will only be included in the study, if they meet all of the following criteria: * Histologically confirmed follicular lymphoma grade 1, 2 or 3A with a biopsy performed within 12 months before study entry and with material available for central review and complementary scientific analyses * Ann Arbor stage III/IV, or stage II not suitable for radiotherapy, or stage II bulky disease * Age ≥ 18 years * No prior lymphoma therapy * Need for start of therapy as defined by at least one of the following criteria: * bulky disease at study entry according to the GELF criteria (nodal or extranodal mass \> 7 cm in its greatest diameter) * B symptoms (fever, drenching night sweats, or unintentional weight loss of \> 10% of normal body weight over a period of 6 months or less) * hematopoietic insufficiency (granulocytopenia \< 1500/µl, Hb \< 10 g/dl, thrombocytopenia \< 100000/µl) * compressive syndrome or high risk for compression syndrome * pleural/peritoneal effusion * symptomatic extranodal manifestations * At least one bi-dimensionally measurable lesion (\> 2 cm in its largest dimension by CT scan or MRI) * Performance status ≤ 2 on the ECOG scale * Adequate hematologic function (unless abnormalities are related to NHL), defined as follows: * Hemoglobin ≥ 9.0 g/dL * Absolute neutrophil count ≥ 1500/µl * Platelet count ≥ 75000/µl * Women are not breast feeding, are using highly effective contraception (see section 11.4.1), are not pregnant, and agree not to become pregnant during participation in the study and during the 18 months thereafter (pregnancy testing is mandatory for premenopausal women). * Men agree not to father a child during participation in the study and during the 18 months thereafter. * Written informed consent Exclusion criteria: Subjects will not be included in the study if any of the following criteria apply: * Transformation to high-grade lymphoma (secondary to "low grade" FL) * Grade 3B follicular lymphoma * Presence or history of CNS disease (either CNS lymphoma or leptomeningeal lymphoma) * Known hypersensitivity to any of the study drugs * Known sensitivity to murine products * Patients with HbA1c \> 8.5 % at Screening * Uncontrolled arterial hypertension despite optimal medical management (per investigator's assessment) * Regular use of corticosteroids during the last 4 weeks, unless administered at a dose equivalent to \< 20 mg/day prednisone or administered as prephase treatment according to study protocol (see section 7.2 of study protocol) * Concomitant use of strong CYP3A4 inhibitors and/or inducers * Prior or concomitant malignancies except: * non-melanoma skin cancer or adequately treated in carcinoma in situ of the cervix * other malignant diseases not specified above which have been curatively treated by surgery alone and from which subject is disease-free for ≥ 5 years without further treatment * Serious disease interfering with a regular therapy according to the study protocol: * Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification * pulmonary (e.g. chronic lung disease with hypoxemia) * endocrine (e.g. severe, not sufficiently controlled diabetes mellitus) * renal insufficiency (unless caused by the lymphoma): creatinine \> 2x normal value and/or creatinine clearance \< 50 ml/min) * impairment of liver function (unless caused by the lymphoma): transaminases \> 3x normal or bilirubin \> 2.0 mg/dl (unless caused by known Morbus Meulengracht \[Gilbert-Meulengracht-Syndrome\]) * Positive test results for chronic HBV infection (defined as positive HBsAg serology) Patients with occult or prior HBV infection (defined as negative HBsAg and positive total HBcAb) may be included if HBV DNA is undetectable, provided that they are willing to undergo monthly DNA testing. Patients who have protective titers of hepatitis B surface antibody (HBsAb) after vaccination or prior but cured hepatitis B are eligible. * Positive test results for hepatitis C (hepatitis C virus \[HCV\] antibody serology testing) Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA. * Clinically significant history of liver disease, including viral or other hepatitis, or cirrhosis * Known history of HIV seropositive status * Patients with a history of confirmed PML * Vaccination with a live vaccine within 28 days prior to registration * Recent major surgery (within 4 weeks prior to the start of Cycle 1) * History of stroke or intracranial hemorrhage within 6 months prior to registration * Serious underlying medical conditions, which could impair the ability of the patient to undergo the treatment offered in the study (e.g. ongoing infection, gastric ulcers, active autoimmune disease) * Treatment within another clinical study within 30 days prior to study entry * Prior organ, bone marrow, or peripheral blood stem cell transplantation * Known or persistent abuse of medication, drugs, or alcohol * Any other co-existing medical or psychological condition that will preclude participation in the study or compromise ability to give informed consent