LP-168 and Obinutuzumab for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) and Variants of This

This is a multicenter parallel two cohort, phase II clinical trial designed to evaluate the combination of obinutuzumab + LP-168 for the treatment of: 1) previously treated, and 2) BTK T474I ( gate keeper mutation) mutated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) patients. The goal is to establish a safe dosing regimen for the combination and to acquire pilot data characterizing the effectiveness of the combination in increasing the depth of response as reflected in the rate of undetectable Minimal Residual Disease (MRD), complete response (CR). If successful, this would support a larger phase II/III study. A gatekeeper cohort of patients is added to further expand understanding of efficacy and translational biology of LP-168 in this patient population that represents a rapidly emerging unmet medical need in CLL.

Patients will receive LP-168 200 mg daily beginning day 1 of therapy for 12 cycles. Within 2 weeks of completing cycle 6, patients will undergo response evaluation that will include labs, CT scan, and bone marrow biopsy. Patients will then continue with LP-168 and then receive obinutuzumab for a total of 6 cycles, beginning cycle 7, days 1, 2, 8 and 15, and then day 1 of cycles 8-12. A minimum of 12 cycles of therapy will be administered. At end of Cycle 12 of therapy, patients will be assessed for treatment response and MRD status by labs, CT scans (if clinically indicated), peripheral blood and bone marrow morphology and using NGS Clonoseq (Adaptive Biotechnologies) for MRD status.

Patients with undetectable minimal residual disease (uMRD) CR at this time will have the option to discontinue therapy. Patients with less than CR or detectable MRD (dMRD) will continue therapy with LP-168 with follow up every 6 months. Patient and investigator may choose to repeat MRD testing from the bone marrow later during the disease course and stop therapy if uMRD is achieved. Patients with disease progression (PD) but who are gaining benefit from the drug can continue therapy per PI discretion.