Clinical trial NCT04993690: A Study of LP-168 in Participants with Relapse or Refractory B-Cell Lymphoma
Official title: A Phase 1 Open-Label Dose Escalation and Expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of LP-168 in Adult Patients with Relapse or Refractory B-Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: B-cell Lymphoma
Lead sponsor: Guangzhou Lupeng Pharmaceutical Company LTD.
Sponsor class: INDUSTRY
First posted: 2021-08-06
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Dose Escalation and determination of MTD; multiple dose levels of LP-168 to be evaluated
Primary purpose: TREATMENT

Brief summary: This is an open-label, multi-center Phase 1/2 study of oral LP-168 in patients with CLL/SLL and NHL who have failed or are intolerant to standard of care.

Detailed description: This study includes 2 parts: phase 1a (LP-168 monotherapy dose escalation) and phase 1b (LP-168 dose expansion). In phase 1a, patients will be enrolled using an 3+3 design. The starting dose of LP-168 in oral tablet form is 100 mg/day (e.g., 100 mg once daily \[QD\]). Once the MTD and/or RP2D is identified in phase 1a dose escalation, enrollment will continue to phase 1b dose expansion. Cycle length will be 28 days.

Eligibility criteria: Key Inclusion Criteria:

* Per 2017 revised WHO lymphoma classification criteria, subject must have either:

Diagnosed with relapsed or refractory DLBCL or FL and require treatment in the opinion of the Investigator and have received 2 lines SOC.

Diagnosed with relapsed or refractory non-Hodgkin's lymphoma associated with B-cell proliferation (such as CLL\\ SLL \\ MCL \\ MZL \\ WM, etc.) in need of treatment in the opinion of the Investigator and have received 1 line SOC.

* Adequate hematologic function.
* Adequate hepatic and renal function.
* Ability to receive study drug therapy orally and willing to receive examinations.
* Willingness of men and women of reproductive potential (defined as following menarche and not postmenopausal \[and 2 years of non-therapy-induced amenorrhea\] or surgically sterile) to observe conventional and effective birth control.

Key Exclusion Criteria:

* According to the 2017 revised WHO Lymphoma Classification Criteria, patients diagnosed with the following diseases: Burkitt lymphoma or Burkitt-like lymphoma, lymphoblastic lymphoma/leukemia, and post-transplant lymphoproliferative disease(PTLD).
* Prior malignancy (other than the disease under study) within the past 3 years, except for curatively treated basal or squamous cell skin cancer, carcinoma in situ of the cervix or breast cancer.
* Subjects who have received the following treatments within 4 weeks or 5 half-lives before the first dose of LP-168:

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 2 weeks before the first dose of LP-168:

Steroids or traditional herbal medicine for antitumor purposes; Strong and moderate CYP3A inhibitors and inducers; All drugs that may cause QTc interval prolongation or torsional tachycardia.

* Disease states where clinical manifestations may be difficult to control, including HIV, HBV, HCV, syphilis positive or active bacterial and fungal infections; Disease affects the central nervous system with obvious symptoms; Autoimmune hemolytic anemia or Idiopathic thrombocytopenic purpura. Any gastrointestinal conditions that may severely affect the study drug absorption or pharmacokinetic parameters.
* Subjects who cannot tolerate urine collection, venipuncture, lymph node biopsy, and bone marrow aspiration.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: Up to 24 Months
measure: Recommended dose for Phase2 (RP2D)
timeFrame: Up to 24 Months
measure: To evaluate the safety of LP-168 by assessing incidence and severity of treatment-emergent adverse events as determined by CTCAE v5.0
timeFrame: Up to 24 Months
Secondary outcomes:
measure: Overall Response Rate
timeFrame: Up to 24 Months
measure: Progression Free Survival
timeFrame: Up to 24 Months
measure: Duration of Response
timeFrame: Up to 24 Months
measure: Pharmacokinetics (PK) As Assessed By Maximum Observed Plasma Concentration (Cmax) Of LP-168
timeFrame: Up to 48 hours post dose
measure: PK As Assessed By Area Under The Plasma Concentration Time Curve From Time 0 To The Time Of The Last Quantifiable Concentration (AUC0-t) Of LP-168
timeFrame: Up to 48 hours post dose
measure: PK As Assessed By Time To Maximum Observed Plasma Concentration (Tmax) Of LP-168
timeFrame: Up to 48 hours post dose
measure: PK As Assessed By Terminal Half-life (t1/2) Of LP-168
timeFrame: Up to 48 hours post dose
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Jun Zhu
role: STUDY_CHAIR
References: