GenFleet Therapeutics, a clinical-stage biotechnology company focusing on cutting-edge therapies in oncology and immunology, announced it has entered into a clinical trial collaboration and supply agreement with BeiGene Switzerland GmbH to start a combination study of GFH009 (CDK9 inhibitor) and BRUKINSA^® (zanubrutinib, BTK inhibitor) in a multicenter phase Ib/II trial treating diffuse large B cell lymphoma (DLBCL). The first patient was dosed in the trial led by prominent Henan Cancer Hospital and Fudan University Shanghai Cancer Center.

Under the terms of the agreement, GenFleet will conduct an open-label, single-arm and multi-center (10 hospitals in China) study of the combination therapy to evaluate the safety and efficacy among relapsed/refractory DLBCL patients. BeiGene will provide clinical drug supplies of BRUKINSA^®(zanubrutinib) for this trial. This study will be the first combination trial conducted by a Chinese biotech to combine CDK9 inhibitor and BTK inhibitor targeting DLBCL.

China's National Cancer Center reports that around 100,000 patients are newly diagnosed non-Hodgkin's lymphoma per year in China, with DLBCL patients accounting for 40-50% of new cases. Currently, R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) is the standard of care in the first line setting for DLBCL globally, but 30-40% of DLBCL patients ultimately progressing into relapsed/refractory stage need more effective treatments.

The trials of GFH009 treating peripheral T-cell lymphoma and acute myeloid leukemia have entered into phase II stage in China and the U.S. respectively. Numerous patients achieved complete or partial response, and significant downregulation of anti-apoptotic proteins such as MYC, MCL1 were observed among patients.

Preclinical research demonstrated GFH009's anti-proliferation effects on various tumor cell lines; the expression level of apoptosis markers including cleaved caspase-3 (CC3) and cleaved PARP increased dose-dependently with GFH009 treatment. According to academic publications, the treatment of CDK9 inhibitor in combination with BTK inhibitor resulted in accelerated induction of cleaved CC3 (the key protein in the cancer-cell killing mechanism of cytotoxic T lymphocytes).

"We are delighted to reach this agreement to move forward the innovative combinational therapy. We appreciate BeiGene's recognition of GenFleet's R&D capabilities and GFH009's clinical potential. GFH009 has shown a promising activity in monotherapy trial and BRUKINSA^®(zanubrutinib) has been approved in scores of markets worldwide; we hope to explore more innovative therapies for relapsed/refractory DLBCL patients with our mutual efforts." stated Jiong Lan, Ph.D, Chief Executive Officer of GenFleet.