a study of lp-118 in patients with advanced tumors

Conditions: Solid Tumor; Lymphoma, Non-Hodgkin

Summary: this is a phase i, multi-center, open-label, dose escalation study to evaluate the safety, tolerability, pharmacokinetics and clinical activity of lp-118 in patients with advanced malignancies, including solid tumors and lymphomas. lp-118 is a bcl-2/bcl-xl small molecule inhibitor.

lp-118 is an oral selective bcl-2 inhibitor with tuned bcl-xl activity, aiming to improve antitumor efficacy and reduce the risk of thrombocytopenia. clinical development of lp-118 includes targeting of relapsed or refractory hematological malignancies and solid tumors. this is a multi-center, open-label, phase 1 dose escalation study of lp-118 in patients with advanced malignancies, including advanced/metastatic solid tumors and relapsed/refractory b cell, t/nk cell lymphomas, to determine the safety, tolerability, pharmacokinetics profile and preliminary anti-tumor efficacy. upon completion of the phase 1 dose escalation study and establishment of maximum tolerated dose (mtd) and recommended phase 2 dose (rp2d), the dose expansion study will be implemented in patients with protocol designated type of disease.

Eligibility criteria:
inclusion criteria: * subjects with histologically or cytologically confirmed malignancy, including either of the following disease: relapsed or refractory lymphomas with at least one measurable disease based on lugano 2014 criteria; or advanced or metastatic solid tumors based on recist v1.1 criteria. * subjects have a life expectancy of ≥12 weeks, and eastern cooperative oncology group (ecog) performance score less than or equal to 1. * subjects must have adequate bone marrow function independent of blood transfusion or growth factor support per local laboratory reference range at screening. * subjects must have adequate coagulation, renal, and hepatic function, per local laboratory reference range at screening. * all acute toxicity from previous anti-tumor treatment or surgery has been alleviated to nci ctcae 5.0 ≤ grade 1. * all enrolled subjects should take medically approved contraceptives during the entire treatment period and within 90 days after the end of treatment. * volunteer and sign informed consent, willing to follow trial protocol. exclusion criteria: * subjects who have undergone allogeneic or autologous hematopoietic stem cell transplantation or car-t cell therapy (except for lymphoma patients who had received autologous stem cell transplantation or car-t cell therapy before 90 days of the first dose of lp-118). * subjects who have received the following treatments within 4 weeks or 5 half-lives before the first dose of study drug: * antitumor therapies including myelosuppressive chemotherapy, targeted therapy, biological therapy and/or immunotherapy; * any investigational treatment; * patients who have undergone major surgery, severe trauma or radiotherapy. * subjects who have received the following treatments within 1 week before the first dose of study drug: * steroids or traditional herbal medicine for antitumor purposes; * strong and moderate cyp3a inhibitors and inducers, grapefruit and grapefruit juice; * any medications that can cause qtc interval prolongation or torsional tachycardia. * solid tumor patients with itp or aiha. * subjects with known bleeding disease or with a history of non-chemotherapy induced thrombocytopenic bleeding or ineffective platelet transfusion within 1 year before the first dose of study drug. * subjects with uncontrollable or ctcae ≥ grade 2 gastrointestinal bleeding occurred within 90 days before the first dose of study drug. * subjects have received the therapeutic dose of anticoagulant or antiplatelet drugs within 1 week before the first dose of study drug. * subjects have any serious and/or uncontrolled systemic disease. * subjects have poor cardiovascular function, in line with new york heart association (nyha) cardiac function classification ≥ 2 or qtcf greater than 450ms (male) or 470ms (female) on ≥ 3 independent ecg. * subjects have disease states where clinical manifestations may be difficult to control, including but not limited to hiv, hbv, hcv, syphilis positive or active bacterial and fungal infections. * lymphoma with primary central nervous system (cns) malignancy or any disease affects the cns. * any gastrointestinal conditions that may severely affect the study drug absorption or pharmacokinetic parameters. * subjects who have known severe allergies to study drugs or any excipients. * subjects who have evidence of a second primary tumor.