A Study of LP-168 in Participants With Relapse or Refractory B-Cell Lymphoma

B-cell Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04993690
• Other study ID #: LP-168-CN101
• Status: Recruiting
• Phase: Phase 1
• Start date: July 6, 2021
• Est. completion date: June 30, 2024

Study information

• Verified date: September 2023
• Source: Guangzhou Lupeng Pharmaceutical Company LTD.
• Contact: Jun Zhu, MD, PhD
• Phone: +86-010-88196596
• Email: zj[@]bjcancer.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 156
• Est. completion date: June 30, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• B-cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell

Intervention

Drug:
• LP-168 tablet
Subjects to take LP-168 orally with 240mL water, without food, Once daily or twice daily

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing
China	Peking University Third Hospital	Beijing	Beijing
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Guangzhou Lupeng Pharmaceutical Company LTD.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD)	Phase 1a	Up to 24 Months
Primary	Recommended dose for Phase2 (RP2D)	Phase Ia/Ib	Up to 24 Months
Primary	To evaluate the safety of LP-168 by assessing incidence and severity of treatment-emergent adverse events as determined by CTCAE v5.0	Phase Ia/Ib	Up to 24 Months
Secondary	Overall Response Rate	To assess the preliminary anti-tumor activity of LP-168 based on overall response rate (ORR) as assessed by investigator and IRC.	Up to 24 Months
Secondary	Progression Free Survival	To assess the preliminary anti-tumor activity of LP-168 based on Progression free survival (PFS) as assessed by the Investigator and IRC	Up to 24 Months
Secondary	Duration of Response	To assess the preliminary anti-tumor activity of LP-168 based on Duration of response (DOR) as assessed by the Investigator and IRC.	Up to 24 Months
Secondary	Pharmacokinetics (PK) As Assessed By Maximum Observed Plasma Concentration (Cmax) Of LP-168	Phase Ia/Ib	Up to 48 hours post dose
Secondary	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	Phase Ia/Ib	Up to 48 hours post dose
Secondary	PK As Assessed By Time To Maximum Observed Plasma Concentration (Tmax) Of LP-168	Phase Ia/Ib	Up to 48 hours post dose
Secondary	PK As Assessed By Terminal Half-life (t1/2) Of LP-168	Phase Ia/Ib	Up to 48 hours post dose