Protocol Amendment 1 Version 4: Study design was updated. Due to the request of the VHP Grounds for non-acceptance (GNA) dated 19 May 2015 clarification on the constitution of the safety review panel was added. Dosing schedule was changed to bi-weekly MOR00208 administration from Cycle 4. Subject inclusion /exclusion criteria were updated . Section 6 was updated due to a sponsor decision that MOR00208 was to be provided centrally only, LEN could be obtained from commercial sources (e.g., reimbursement or centrally) and other medications (e.g., pre-medication agents) were provided by participating site. Clarification on patient compliance was added. (Safety Assessments was deleted as the section was redundant. The collection of ECG RR intervals was added in the Section 7.2.5 because ECG RR intervals were needed for QTc calculations. Clarifications were made about the dipstick urine pregnancy test; sensitivity of the test was added. Re-wording and clarification was added concerning the control of blood glucose for obtaining assessable PET scan and conditions for PET/CT to replace CT while measuring the tumour. The collection of ECG QT intervals was added in Section 10.7.3.

Protocol Amendment 2 Version 5: The investigational treatment continuation into subsequent cycle was updated to remove the need to have a creatinine clearance of at least 60 mL/min for subsequent cycles, since this was not required as per LEN SmPC. The target subject population/inclusion criteria (also reflected in Section 5.1 on study design and investigational plan). The need to have 60 mL/min at screening/baseline remained unchanged. EOT Visit added the need to perform an Unscheduled Visit, covering all the assessments for the EOT Visit after disease progression for patients who progressed but continued antibody therapy with MOR00208, at the discretion of the treating investigator. Corresponding text about this visit was added to several other places as applicable, including schedule of assessments. HBV serology was required monthly for all patients in the previous protocol version. This was changed to monthly only for those patients who had anti-HBc antibody positive (and HBV-DNA negative) at screening. Use of corticosteroids during study was elaborated and allowed short courses of corticosteroids for symptomatic relief. Repeated laboratory assessments during screening period was updated to allow one repeat of serum chemistry and haematology values in case of possible lab error, or due to temporarily abnormal lab values that could be attributed to a patient’s condition (e.g.dehydration) and could be corrected. Administrative changes to the Clinical Program Leader and change of the CRO including SAE reporting were also made.

Protocol Amendment 3 Version 6: The antibody treatment with MOR00208 was extended beyond Cycle 24 until progression because the previous version of the protocol allowed an extended treatment with MOR00208 for subjects with an ongoing response of CR or PR for 24 cycles. The imaging frequency after Cycle 24 while on treatment with MOR00208 was amended to reduce the burden to subjects and investigators. Central Laboratory assessments to once a year were removed after Cycle 24 in order to simplify the study conduct. Change of sponsor signatories and change of sponsor address. Disease assessment by CT/MRI during additional treatment phase. Clarification of time points of scans during Cycle 13-24 was added. Schedule of assessments was adapted to be consistent with extended antibody treatment with MOR00208 beyond Cycle 24 until progression, imaging frequency after Cycle 24 while on treatment with MOR00208. Minor editorial changes and clarifications were updated. a)Data from previous ongoing and completed studies updated in Section 1.4.2 Safety of MOR00208. b) For subjects who were lost to follow-up, at least three attempts of contact by the site should have been made and documented in the source data c) Clarification of follow-up visits for OS occurring via telephone. d) Clarification of the name of the Drug Preparation Manual. e) Using actual body weight prior to each MOR00208 infusion was allowed, if this was preferred by investigators f) Clarification on treatment consisting of LEN and MOR00208 combination. This was administered up to twelve 28-day cycles at specified dose levels rather than until disease progression or discontinuation.

Protocol Amendment 5 Version 8: The study duration per subject was at least 5 years including periods of screening (up to 28 days from signature of the Informed Consent Form (ICF), the treatment period (maximum 12 cycles for LEN + MOR00208 followed by MOR00208 monotherapy thereafter) and the survival follow-up phase. MOR00208 was administered until disease progression. The safety follow up period was extended to be allowed until the end of the study to provide important data on long term safety and survival outcomes. The end of the study (EOS) was defined as the date of the last visit of the last subject completing 5 years study duration including survival follow-up. If any subject was on treatment with MOR00208 at the end of the study and MOR00208 was not yet commercially available, subjects would be switched to alternative methods of supply with MOR00208. Upon study closure, MorphoSys would notify the applicable regulatory agencies in accordance with local requirements.