Clinical trial NCT05025358: A Study of LP-118 in Patients with Advanced Tumors
Official title: A Phase I Study on Safety, Tolerance, Pharmacokinetics and Preliminary Efficacy of LP-118 in Patients with Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Solid Tumor
Lymphoma, Non-Hodgkin
Lead sponsor: Guangzhou Lupeng Pharmaceutical Company LTD.
Sponsor class: INDUSTRY
First posted: 2021-08-27
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Maximum tolerated dose (MTD)
timeFrame: Up to 24 months
measure: Adverse events
timeFrame: Up to 24 months
measure: Recommended phase II dose (RP2D)
timeFrame: Up to 24 months
measure: PK evaluation of area under the plasma concentration versus time curve (AUC) of LP-118
timeFrame: Up to Cycle 6 (each cycle is 28 days)
measure: PK evaluation of peak plasma concentration (Cmax) of LP-118
timeFrame: Up to Cycle 6 (each cycle is 28 days)
measure: PK evaluation of time to maximum concentration (Tmax) of LP-118
timeFrame: Up to Cycle 6 (each cycle is 28 days)
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: Up to 24 months
measure: Duration of response (DOR)
timeFrame: Up to 24 months
measure: Progression-free survival (PFS)
timeFrame: Up to 24 months
measure: Overall survival
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Jinan University
state: Guangdong
city: Wuhan
country: China
facility: Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
state: Hubei
city: Hangzhou
country: China
facility: First Affiliated Hospital of Zhejiang University School of Medicine
state: Zhejiang
Study officials:
affiliation: Guangdong Provincial People's Hospital
name: Yilong Wu, MD
role: STUDY_CHAIR
References: