Clinical trial NCT04504708: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Non-hodgkin Lymphoma
Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Lead sponsor: Hangzhou Zenshine Pharmaceuticals Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-08-07
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Primary outcomes:
measure: Defining the recommended Phase 2 dose (RP2D) of ZX-101A.
timeFrame: 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.
measure: Safety and tolerability of ZX-101A
timeFrame: From first dose of ZX-101A through 28 days after the last ZX-101A treatment (up to 2 years); each cycle is 28 days.
Secondary outcomes:
measure: Peak Plasma Concentration of ZX-101A
timeFrame: Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5
measure: Area under the plasma concentration of ZX-101A
timeFrame: Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5
measure: Half-life of ZX-101A
timeFrame: Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5
measure: Phospho-AKT (p-AKT) levels in whole blood
timeFrame: Days 1 and 2 of Cycle 1 (each cycle is 28 days)
measure: Objective response rate (ORR)
timeFrame: Up to 2 years
measure: Duration of response (DoR)
timeFrame: Up to 2 years
measure: Progression free survival (PFS)
timeFrame: Up to 2 years
measure: Overall survival (OS)
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Tucson
country: United States
facility: ACRC/Arizona Clinical Research Center, Inc.
state: Arizona
city: Long Beach
country: United States
facility: Innovative Clinical Research Institute
state: California
city: Brick
country: United States
facility: New Jersey Center for Cancer Research
state: New Jersey
city: Toledo
country: United States
facility: University of Toledo Precision Oncology Research
state: Ohio
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
Study officials:
affiliation: Zenshine Pharmaceutical, Inc.
name: Xiaolin Qin, PhD
role: STUDY_DIRECTOR
References: