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

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

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.

Study Overview

• Status: Recruiting
• Conditions: B-cell Lymphoma
• Intervention / Treatment: Drug: LP-168 tablet

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.

• Study Type: Interventional
• Enrollment (Estimated): 156
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jun Zhu, MD, PhD; Phone Number: +86-010-88196596; Email: zj@bjcancer.org
• Study Contact Backup: Name: Yuqin Song, MD, PhD

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Recruiting
      • Beijing Cancer Hospital
      • Contact: Yuqin Song; Phone Number: +861088196596; Email: SongYQ_VIP@163.com
    • Beijing, Beijing, China, 100089
      • Recruiting
      • Peking University Third Hospital
      • Contact: Hongmei Jing, M.D.; Phone Number: +861082265531; Email: hongmei_jing@163.com
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-Sen University Cancer Center
      • Contact: Qingqing Cai, M.D.; Phone Number: +862087342823; Email: caiqq@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase I Dose Escalation; Dose Escalation and determination of MTD; multiple dose levels of LP-168 to be evaluated	Drug: LP-168 tablet; Subjects to take LP-168 orally with 240mL water, without food, Once daily or twice daily
Experimental: Phase I Dose Expansion A; CLL/SLL patients treated with prior regimens.	Drug: LP-168 tablet; Subjects to take LP-168 orally with 240mL water, without food, Once daily or twice daily
Experimental: Phase I Dose Expansion B; CLL/SLL patients with no prior therapy.	Drug: LP-168 tablet; Subjects to take LP-168 orally with 240mL water, without food, Once daily or twice daily
Experimental: Phase I Dose Expansion C; MCL patients treated with prior regimens.	Drug: LP-168 tablet; Subjects to take LP-168 orally with 240mL water, without food, Once daily or twice daily
Experimental: Phase I Dose Expansion D; WM patients treated with prior regimens.	Drug: LP-168 tablet; Subjects to take LP-168 orally with 240mL water, without food, Once daily or twice daily
Experimental: Phase I Dose Expansion E; MZL patients treated with prior regimens.	Drug: LP-168 tablet; Subjects to take LP-168 orally with 240mL water, without food, Once daily or twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose (MTD)	Phase 1a	Up to 24 Months
Recommended dose for Phase2 (RP2D)	Phase Ia/Ib	Up to 24 Months
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
Pharmacokinetics (PK) As Assessed By Maximum Observed Plasma Concentration (Cmax) Of LP-168	Phase Ia/Ib	Up to 48 hours post dose
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
PK As Assessed By Time To Maximum Observed Plasma Concentration (Tmax) Of LP-168	Phase Ia/Ib	Up to 48 hours post dose
PK As Assessed By Terminal Half-life (t1/2) Of LP-168	Phase Ia/Ib	Up to 48 hours post dose

Collaborators and Investigators

• Sponsor: Guangzhou Lupeng Pharmaceutical Company LTD.
• Investigators: Study Chair: Jun Zhu, Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2021
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: July 27, 2021
• First Submitted That Met QC Criteria: August 3, 2021
• First Posted (Actual): August 6, 2021

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 26, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell
• Other Study ID Numbers: LP-168-CN101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No