Dose-Escalation and Dose-Expansion Study of ZX-101A in Patients With Relapsed/Resistant or Refractory Advanced Hematologic Malignancies

A Phase 1/2a, Dose-Escalation and Dose-Expansion Study of ZX-101A in Patients With Relapsed/Resistant or Refractory Advanced Hematologic Malignancies

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).

Study Overview

• Status: Terminated
• Conditions: Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Non-hodgkin Lymphoma
• Intervention / Treatment: Drug: ZX-101A

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
    • Tucson, Arizona, United States, 85715
      • Acrc/Arizona Clinical Research Center, Inc.
  • California
    • Long Beach, California, United States, 90804
      • Innovative Clinical Research Institute
  • New Jersey
    • Brick, New Jersey, United States, 08724
      • New Jersey Center for Cancer Research
  • Ohio
    • Toledo, Ohio, United States, 43614
      • University of Toledo Precision Oncology Research
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ZX-101A Dose Level 1; Starting dose (SD) of ZX-101A administered orally once daily in a 28-day cycle	Drug: ZX-101A; Once daily, oral dosing of ZX-101A at the assigned dose level for 28 consecutive days in a 28-day cycle
Experimental: ZX-101A Dose Level 2; 2-times the SD of ZX-101A administered orally once daily in a 28-day cycle	Drug: ZX-101A; Once daily, oral dosing of ZX-101A at the assigned dose level for 28 consecutive days in a 28-day cycle
Experimental: ZX-101A Dose Level 3; 3-times the SD of ZX-101A administered orally once daily in a 28-day cycle	Drug: ZX-101A; Once daily, oral dosing of ZX-101A at the assigned dose level for 28 consecutive days in a 28-day cycle
Experimental: ZX-101A Dose Level 4; 4-times the SD of ZX-101A administered orally once daily in a 28-day cycle	Drug: ZX-101A; Once daily, oral dosing of ZX-101A at the assigned dose level for 28 consecutive days in a 28-day cycle
Experimental: ZX-101A Dose Level 5; 5-times the SD of ZX-101A administered orally once daily in a 28-day cycle	Drug: ZX-101A; Once daily, oral dosing of ZX-101A at the assigned dose level for 28 consecutive days in a 28-day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Defining the recommended Phase 2 dose (RP2D) of ZX-101A.	To assess number of patients experiencing dose-limiting toxicities (DLTs) in Part 1.	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 and tolerability of ZX-101A	To examine the incidence of clinical and laboratory adverse events after multiple doses of ZX-101A in Parts 1 and 2	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Plasma Concentration of ZX-101A	To evaluate the maximum observed concentration (Cmax) after single and repeated oral, once daily doses of ZX-101A	Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5
Area under the plasma concentration of ZX-101A	To evaluate the area under the curve (AUC) plasma-concentration after single and repeated oral, once daily doses of ZX-101A	Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5
Half-life of ZX-101A	To evaluate the half-life of ZX-101A after single and repeated oral, once daily doses of ZX-101A	Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5
Phospho-AKT (p-AKT) levels in whole blood	To evaluate the differences phospho-AKT (p-AKT) levels in whole blood before and after single oral dose of ZX-101A.	Days 1 and 2 of Cycle 1 (each cycle is 28 days)
Objective response rate (ORR)	To evaluate the objective response rate (ORR) as determined by the specific disease response criteria	Up to 2 years
Duration of response (DoR)	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	Up to 2 years
Progression free survival (PFS)	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	Up to 2 years
Overall survival (OS)	To examine the overall survival (OS), defined as time from the date of first dose of study treatment to death due to any cause	Up to 2 years

Collaborators and Investigators

• Sponsor: Hangzhou Zenshine Pharmaceuticals Co., Ltd.
• Investigators: Study Director: Xiaolin Qin, PhD, Zenshine Pharmaceutical, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2021
• Primary Completion (Actual): July 8, 2022
• Study Completion (Actual): July 8, 2022

Study Registration Dates

• First Submitted: July 25, 2020
• First Submitted That Met QC Criteria: August 5, 2020
• First Posted (Actual): August 7, 2020

Study Record Updates

• Last Update Posted (Actual): October 21, 2022
• Last Update Submitted That Met QC Criteria: October 19, 2022
• Last Verified: October 1, 2022

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; Neoplasms by Site; Hematologic Diseases; Leukemia, Lymphoid; Leukemia; Leukemia, B-Cell; Lymphoma; Hematologic Neoplasms; Leukemia, Lymphocytic, Chronic, B-Cell
• Other Study ID Numbers: ZX-101A-101

Drug and device information, study documents

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