Lymphoma, Non-Hodgkin, Solid Tumor
Conditions
Brief 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.
Detailed 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.
Interventions
DRUGLP-118 tablet
Subjects will administered orally with LP-118 tablet at the designated dose once daily, using approximately 240 mL of water during a meal or within 30 minutes after a meal, 28 days per cycle. The treatment will continue until progressive disease, unacceptable toxicity, etc.
Sponsors
Guangzhou Lupeng Pharmaceutical Company LTD.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PK evaluation of time to maximum concentration (Tmax) of LP-118 | Up to Cycle 6 (each cycle is 28 days) | Tmax indicates the time taken to reach the maximum drug concentration (i.e. Cmax). |
| Adverse events | Up to 24 months | The incidence and severity of adverse events as assessed by NCI CTCAE v5.0. |
| Recommended phase II dose (RP2D) | Up to 24 months | The safe dose that demonstrates the greatest pharmacological activity. |
| PK evaluation of area under the plasma concentration versus time curve (AUC) of LP-118 | Up to Cycle 6 (each cycle is 28 days) | AUC indicates the extent of exposure to LP-118 and its clearance rate from the body. |
| PK evaluation of peak plasma concentration (Cmax) of LP-118 | Up to Cycle 6 (each cycle is 28 days) | Cmax indicates the highest drug concentration in the blood after LP-118 administration. |
| Maximum tolerated dose (MTD) | Up to 24 months | The highest dose that does not cause unacceptable side effects or overt toxicities which will be assessed by NCI CTCAE v5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | Up to 24 months | The time from first dose to the date of death from any cause. |
| Overall response rate (ORR) | Up to 24 months | The proportion of patients who have a partial or complete response after LP-118 treatment. |
| Duration of response (DOR) | Up to 24 months | The time from first documented response to disease progression or death. |
| Progression-free survival (PFS) | Up to 24 months | The time from first dose to disease progression or death, whichever occurs first. |
Countries
China
Outcome results
None listed