Overview
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.
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.