A Phase I Study on Safety, Tolerance, Pharmacokinetics and Preliminary Efficacy of LP-118 in Patients With Advanced Malignancies
Overview
- Phase
- Phase 1
- Intervention
- LP-118 tablet
- Conditions
- Solid Tumor
- Sponsor
- Guangzhou Lupeng Pharmaceutical Company LTD.
- Enrollment
- 68
- Locations
- 4
- Primary Endpoint
- Recommended phase II dose (RP2D)
- Status
- Completed
- Last Updated
- 4 months ago
Overview
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.
Investigators
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
- •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
- •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.
Arms & Interventions
LP-118
The classic "3+3" design at dose levels of 50mg, 100mg, 200mg, 300mg, 400mg and 500mg will be implemented in this study.
Intervention: LP-118 tablet
Outcomes
Primary Outcomes
Recommended phase II dose (RP2D)
Time Frame: 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
Time Frame: 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.
Adverse events
Time Frame: Up to 24 months
The incidence and severity of adverse events as assessed by NCI CTCAE v5.0.
PK evaluation of time to maximum concentration (Tmax) of LP-118
Time Frame: Up to Cycle 6 (each cycle is 28 days)
Tmax indicates the time taken to reach the maximum drug concentration (i.e. Cmax).
Maximum tolerated dose (MTD)
Time Frame: 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.
PK evaluation of peak plasma concentration (Cmax) of LP-118
Time Frame: Up to Cycle 6 (each cycle is 28 days)
Cmax indicates the highest drug concentration in the blood after LP-118 administration.
Secondary Outcomes
- Progression-free survival (PFS)(Up to 24 months)
- Duration of response (DOR)(Up to 24 months)
- Overall response rate (ORR)(Up to 24 months)
- Overall survival(Up to 24 months)