A Study of LP-118 in Patients With Advanced Tumors

Guangzhou Lupeng Pharmaceutical Company

Status and phase

Completed

Phase 1

Conditions

Solid Tumor

Lymphoma, Non-Hodgkin

Treatments

Drug: LP-118 tablet

Study type

Interventional

Funder types

Industry

Identifiers

NCT05025358

LP-118-CN101

Details and patient eligibility

About

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.

Full description

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.

Enrollment

68 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.