Description:
ZX-101A-101 is a Phase 1/2a, first-in-human, open-label, multicenter, multiple-ascending dose
study to investigate the safety, tolerability, pharmacokinetics, pharmacodynamic, and
preliminary antitumor activity of ZX-101A administered orally (PO) once daily (QD) in 28-day
cycles in patients with relapsed/resistant or refractory advanced hematologic malignancies
[Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL), indolent NHL, and other
NHL subtypes).
Title
- Brief Title: Dose-Escalation and Dose-Expansion Study of ZX-101A in Patients With Relapsed/Resistant or Refractory Advanced Hematologic Malignancies
- Official Title: A Phase 1/2a, Dose-Escalation and Dose-Expansion Study of ZX-101A in Patients With Relapsed/Resistant or Refractory Advanced Hematologic Malignancies
Clinical Trial IDs
- ORG STUDY ID:
ZX-101A-101
- NCT ID:
NCT04504708
Conditions
- Non-hodgkin Lymphoma
- Chronic Lymphocytic Leukemia
- Small Lymphocytic Lymphoma
Interventions
Drug | Synonyms | Arms |
---|
ZX-101A | | ZX-101A Dose Level 1 |
Purpose
ZX-101A-101 is a Phase 1/2a, first-in-human, open-label, multicenter, multiple-ascending dose
study to investigate the safety, tolerability, pharmacokinetics, pharmacodynamic, and
preliminary antitumor activity of ZX-101A administered orally (PO) once daily (QD) in 28-day
cycles in patients with relapsed/resistant or refractory advanced hematologic malignancies
[Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL), indolent NHL, and other
NHL subtypes).
Detailed Description
The ZX-101A-101 study will consist of 2 parts:
- Part 1: ZX-101A Dose Escalation
- Part 2: ZX-101A Dose Expansion
The Part 1 (dose escalation) of the study is designed to determine the safety and
tolerability of ZX-101A administered orally once daily in 28-day cycles. The Part 2 (dose
expansion) of the study is designed to further investigate the safety, tolerability,
pharmacokinetics and pharmacodynamic and clinical activities of ZX-101A administered orally
once daily in 28-day cycles at the selected recommended Phase 2 dose (RP2D).
Results of clinical findings in patients in the dose-escalation portion of the study will be
reviewed to identify conditions (or genetic characteristics) most likely to respond to
ZX-101A. These select types of hematologic malignancies will be enrolled in cohorts in the
dose-expansion part of the study.
Male or female patients who are 18 years of age or older with relapsed/resistant or
refractory advanced hematologic malignancies (CLL/SLL, iNHL, and other NHL subtypes) will be
included in the study provided that all inclusion and exclusion criteria are satisfied.
Up to three cohorts are planned in Part 2 - Dose Expansion of the study: 1)
relapsed/resistant or refractory Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic
Lymphoma (SLL), 2) relapsed/resistant or refractory indolent Non- Hodgkin's Lymphoma (iNHL),
and based on emerging data from Part 1-Dose Expansion, a third cohort consisting of other
types of NHL may be included.
Trial Arms
Name | Type | Description | Interventions |
---|
ZX-101A Dose Level 1 | Experimental | Starting dose (SD) of ZX-101A administered orally once daily in a 28-day cycle | |
ZX-101A Dose Level 2 | Experimental | 2-times the SD of ZX-101A administered orally once daily in a 28-day cycle | |
ZX-101A Dose Level 3 | Experimental | 3-times the SD of ZX-101A administered orally once daily in a 28-day cycle | |
ZX-101A Dose Level 4 | Experimental | 4-times the SD of ZX-101A administered orally once daily in a 28-day cycle | |
ZX-101A Dose Level 5 | Experimental | 5-times the SD of ZX-101A administered orally once daily in a 28-day cycle | |
Eligibility Criteria
Inclusion Criteria:
- Males and females who are ≥ 18 years old
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
- Failed at least 2 prior systemic standard therapies.
- Histopathological confirmed diagnosis of CLL/SLL, indolent NHL,and other NHL subtypes.
- Documented active disease that is relapsed/resistant or refractory requiring treatment
after established therapy shown to have clinical benefit.
- Acceptable bone marrow, kidney, and liver function.
- No transfusion or cytokine support for ≥ 2 weeks before initiating study treatment.
- Ability to swallow and retain oral medications (see exclusion criteria #20 below).
- Negative serum pregnancy test in women of childbearing potential at Screening.
- Women of childbearing potential and men who partner with a woman of childbearing
potential must agree to use effective contraceptive methods.
- Men must agree to no sperm donations during the study and for 3 months after the last
dose of ZX-101A.
- Understands the requirements of the study (e.g. periodic imaging studies, periodic
blood sampling, bone marrow studies), is willing to comply with all study procedures
and signed the Institutional Review Board (IRB)-approved informed consent.
Exclusion Criteria:
- Received investigational study drug within 28 days (or 5 half-lives, whichever is
longer).
- Concurrent participation in another therapeutic treatment trial.
- Received approved anti-cancer drugs within 21 days (42 days for nitrosoureas) or 5
half-lives, whichever is longer.
- Ongoing immunosuppression for chronic conditions.
- Known active hepatitis B virus (HBV), hepatitis C virus (HCV), or HIV infection.
- Any concurrent uncontrolled illness.
- Has not recovered from adverse events from prior anti-cancer treatment (with exception
of alopecia).
- Pregnant or breast-feeding or planning to conceive or father children within the
projected duration of the study.
- Major surgery within 4 weeks prior to first dose of study treatment.
- Radiation treatment within 2 weeks prior to first dose of study treatment.
- Gastrointestinal dysfunction, including motility or malabsorption syndromes or
inflammatory bowel disease which could limit absorption of study drug.
- Active or prior pneumonitis or interstitial lung disease.
Other inclusion and exclusion criteria may apply.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Defining the recommended Phase 2 dose (RP2D) of ZX-101A. |
Time Frame: | From Day 1 of Cycle 1 through the end of the DLT evaluation period (28 days for the first two Dose Levels and 84 days for Dose Levels 3, 4 and 5); each cycle is 28 days. |
Safety Issue: | |
Description: | To assess number of patients experiencing dose-limiting toxicities (DLTs) in Part 1. |
Secondary Outcome Measures
Measure: | Peak Plasma Concentration of ZX-101A |
Time Frame: | Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5 |
Safety Issue: | |
Description: | To evaluate the maximum observed concentration (Cmax) after single and repeated oral, once daily doses of ZX-101A |
Measure: | Area under the plasma concentration of ZX-101A |
Time Frame: | Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5 |
Safety Issue: | |
Description: | To evaluate the area under the curve (AUC) plasma-concentration after single and repeated oral, once daily doses of ZX-101A |
Measure: | Half-life of ZX-101A |
Time Frame: | Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5 |
Safety Issue: | |
Description: | To evaluate the half-life of ZX-101A after single and repeated oral, once daily doses of ZX-101A |
Measure: | Phospho-AKT (p-AKT) levels in whole blood |
Time Frame: | Days 1 and 2 of Cycle 1 (each cycle is 28 days) |
Safety Issue: | |
Description: | To evaluate the differences phospho-AKT (p-AKT) levels in whole blood before and after single oral dose of ZX-101A. |
Measure: | Objective response rate (ORR) |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | To evaluate the objective response rate (ORR) as determined by the specific disease response criteria |
Measure: | Duration of response (DoR) |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | To examine the duration of response (DoR), defined as time from the date of first documentation of response to the date of the first documentation of progressive disease (PD), or death due to any cause |
Measure: | Progression free survival (PFS) |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | To examine the the progression free survival (PFS), defined as time from the date of first dose of study treatment to the first date of documentation of PD, or death due to any cause |
Measure: | Overall survival (OS) |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | To examine the overall survival (OS), defined as time from the date of first dose of study treatment to death due to any cause |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Hangzhou Zenshine Pharmaceuticals Co., Ltd. |
Last Updated
August 30, 2021