Background: Ibrutinib, a Bruton's tyrosine kinase inhibitor (BTKi), is an important treatment option for patients (pts) with CLL/SLL. Pts who progress early on ibrutinib are difficult to treat and have poor outcomes. Thus, ibrutinib-pretreated pts, including pts with ibrutinib intolerance, are in urgent need of novel therapeutic options. MOR208, an Fc-engineered, humanized, monoclonal antibody targeting the B-cell receptor CD19 (highly expressed on lymphoid malignancies) was well tolerated in a phase I study in relapsed or refractory (R/R) CLL/SLL and showed promising single-agent activity. In preclinical models, MOR208 showed synergistic activity with idelalisib (PI3Kδ inhibitor), providing a rationale for testing this combination in a clinical study. Methods: This open-label, multicenter, single-arm, phase II study has a safety run-in with a 3+7 design. Main inclusion criteria are: adult pts with CLL/SLL, R/R disease while on BTKi therapy given as single-agent or combination therapy for at least one month or intolerant to such therapy, ECOG performance status of 0–2, adequate bone marrow, hepatic and renal function. Main exclusion criteria are: BTKi treatment within 5 days prior to study drug dosing, lymphoma-specific therapy within 14 days prior to dosing, prior treatment with a CD19-targeted therapy or a PI3K inhibitor. MOR208 with idelalisib is given until disease progression, unacceptable toxicity, death or loss to follow-up, for up to a maximum of 24 cycles. MOR208 12 mg/kg is given intravenously, weekly for the first 3 cycles, and then every 2 weeks. Idelalisib is taken orally, 150 mg twice-daily. Primary endpoint is overall response rate (central review) assessed by International Workshop on CLL criteria and the Lugano criteria for SLL. Key secondary endpoints include progression-free survival, overall survival, duration of response, safety, pharmacokinetics, MOR208 immunogenicity and patient-reported outcomes. Exploratory biomarker analyses will also be performed. Enrollment and treatment are underway; 120 pts are planned. Clinical trial information: NCT02639910