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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05659732




Registration number
NCT05659732
Ethics application status
Date submitted
30/11/2022
Date registered
21/12/2022
Date last updated
19/07/2023

Titles & IDs
Public title
A Study of PEP07 (Checkpoint Kinase 1 Inhibitor) in Patients With Advanced Cancer
Scientific title
A Phase 1b Study of PEP07 (Checkpoint Kinase 1 Inhibitor) in Patients With Advanced Cancer
Secondary ID [1] 0 0
PEP07-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia 0 0
Lymphoma, Mantle-Cell 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PEP07

Experimental: PEP07 Monotherapy (Arm A) - The dose finding of PEP07 monotherapy consists of an accelerated dose escalation followed by a standard "3+3" dose escalation. Accelerated titration will continue until 1 patient experiences a DLT, or = grade 2 AE related to PEP07 (except for hematologic toxicities) at any dose level, after which, additional 2 patients will be enrolled in the same cohort, and the study will be switched to a 3+3 scheme.
Expansion cohorts with 12 patients will be opened for Arm A at the RP2D once efficacy signal is observed at this level.


Treatment: Drugs: PEP07
PEP07 is a selective Chk1 inhibitor maleate drug which is supplied as a hard gelatin capsule. PEP07 will be provided as 20 mg and 150 mg strength capsules to be administrated orally. Patients allocated to different dose levels of PEP07 monotherapy will receive either 20 mg or 150 mg oral capsules for 2 consecutive days followed by 5 days treatment off (2-on/5-off) schedule every week, 4 weeks as a treatment cycle.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To assess the safety and tolerability of PEP07 administered orally as a single dose and at escalating dose levels, and, to determine the dose-limiting toxicity (DLT) of study treatment in patients with AML and MCL.
Timepoint [1] 0 0
4 weeks after first dosing
Primary outcome [2] 0 0
To determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of PEP07 monotherapy.
Timepoint [2] 0 0
4 weeks after first dosing
Secondary outcome [1] 0 0
To assess the AUC from time zero to infinity (AUC0-inf) of single and multiple oral PEP07 as a monotherapy.
Timepoint [1] 0 0
6 months
Secondary outcome [2] 0 0
To assess the Time to maximum (peak) plasma concentration (Tmax) of single and multiple oral PEP07 as a monotherapy.
Timepoint [2] 0 0
6 months
Secondary outcome [3] 0 0
To assess the apparent half-life (t1/2) of single and multiple oral PEP07 as a monotherapy.
Timepoint [3] 0 0
6 months
Secondary outcome [4] 0 0
To assess the Maximum observed concentration (Cmax) of single and multiple oral PEP07 as a monotherapy.
Timepoint [4] 0 0
6 months
Secondary outcome [5] 0 0
To assess preliminary evidence of anti-tumor activity of PEP07 by progression free survival (PFS).
Timepoint [5] 0 0
after first dosing to disease progression
Secondary outcome [6] 0 0
To assess preliminary evidence of anti-tumor activity of PEP07 by progression free survival (PFS).
Timepoint [6] 0 0
after first dosing to disease progress

Eligibility
Key inclusion criteria
1. Must be = 18 years of age.

2. Must have histological or cytological confirmation advanced hematologic malignancy
including:

- Relapsed or refractory AML (by the 5th edition of World Health Organization [WHO]
classification of Hematolymphoid tumors)

- OR Relapsed or refractory MCL and have received at least two prior lines of
treatment, including chemoimmunotherapy and BTKi and at least 1 measurable site
of disease according to Revised Response Criteria for Malignant Lymphoma.

3. Must have Eastern Cooperative Oncology Group (ECOG) Performance score of 0 to 2.

4. Must have adequate renal function as demonstrated by a calculated creatinine clearance
= 50 mL/min; determined via urine collection for 24-hour creatinine clearance or by
the Cockcroft Gault formula.

5. Must have adequate liver function as demonstrated by:

- aspartate aminotransferase (AST) = 2.5 × ULN

- alanine aminotransferase (ALT) = 2.5 × ULN

- bilirubin = 1.5 × ULN (unless considered due to leukemic organ involvement.
Patients with Gilbert's Syndrome may have had a bilirubin > 1.5 × ULN per
discussion between the PI or designee and sponsor)

6. Left ventricular ejection fraction (LVEF) = 50% measured by multiple-gated acquisition
(MUGA) or echocardiogram.

7. Previous AEs have been improved to baseline or Grade = 1 NCI CTCAE v5.0.

8. Female patients with reproductive potential must have a negative serum pregnancy test
7 days prior to the administration of PEP07.

9. Patients will be required to have a Covid negative test either via reverse
transcriptase polymerase chain reaction (RTPCR) or a rapid antigen test (RAT) test on
Day -7/Day 1.

10. Provision of signed and dated informed consent form.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Pregnant or breastfeeding females

2. Females of childbearing potential and males whose partners are of childbearing
potential who do not agree to the use of 2 forms of highly effective contraception
during the treatment period and for 120 days after the last dose of PEP07.

3. Patients who have received anti-cancer therapy including chemotherapy, radiotherapy,
hormonal, or any investigational therapy within 14 days or 5 half-lives (whichever is
shorter), or immunotherapy within 30 days prior to the first dose of PEP07. Patients
who have received hydroxyurea or dexamethasone at any time prior to the start of study
treatment is an exception to this criterion.

4. Patients who have undergone allogeneic hematopoietic stem cell transplant (HSCT)
within 60 days of PEP07 treatment.

5. Patients who have received strong or moderate CYP3A4 inhibitors or inducers such as
ketoconazole, erythromycin, netupitant, isavuconazole etc. within 5 half-lives or 7
days (whichever is the shortest) prior to the initiation of study treatment.

6. Viral infection with HIV or viral hepatitis type B or C which require antiviral
therapy and/or have positive serology test of hepatitis B surface antigen [HBsAg (+)]
with HBV DNA = 1000 IU/mL, or hepatitis C virus antibody [anti-HCV Ab (+)] with HCV
RNA (+). If a patient is HBsAg (+) then HBV DNA needs to be tested. If a patient is
anti-HCV Ab (+) then the patient needs to be followed for HCV RNA (-) to be enrolled.

7. Uncontrolled systemic infection /or requiring isolation.

8. Patients with previous history of other malignant diseases within the last 5 years
(other than adequately treated non-melanotic skin cancer, in-situ carcinoma of the
uterine cervix or myelodysplastic syndromes).

9. Patients with ongoing = Grade 2 (CTCAE v5.0) toxicity (except alopecia and hot
flashes) related to previous treatment.

10. Patients with baseline QTc interval > 450 msec (i.e., CTCAE Grade = 2) at screening
(within 28 days prior to 1st dose of PEP07, mean of triplicate readings within
approximately 5 minutes).

11. Patients with cardiovascular disability status of New York Heart Association (NYHA) =
Class III, left ventricular ejection fraction < 45 % at baseline, history of cardiac
ischemia within the past 6 months, or prior history of cardiac arrhythmia requiring
treatment.

12. Patients who have undergone any major surgery within 3 weeks prior to first study drug
administration after enrollment.

13. Patients with known active central nervous system (CNS) or leptomeningeal involvement.

14. Patients who have had any of the following within 6 months prior to first
administration of PEP07 after enrollment: myocardial infarction, severe/unstable
angina pectoris, coronary/peripheral artery bypass graft, symptomatic congestive heart
failure, cerebrovascular accident or transient ischemic attack, or seizure disorder.

15. Have a history of hypersensitivity reactions or allergic reactions to PEP07 excipients
and components.

16. Patients with other medical or psychiatric condition that, in the opinion of the
investigator, might interfere with the patient's participation in the trial or
interfere with the interpretation of trial results.

17. Others who are ineligible to participate in this clinical study as determined by the
PI or designee.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/07/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2025
Actual
Sample size
Target
32
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Monash Medical Centre - Clayton
Recruitment postcode(s) [1] 0 0
3168 - Clayton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
PharmaEngine
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The goal of this clinical trial is

- To assess the safety and tolerability of PEP07 administered orally as a single dose and
at escalating dose levels, and, to determine the dose-limiting toxicity (DLT) of study
treatment in patients with Acute Myeloid Leukemia (AML) and Mantle Cell Lymphoma (MCL).

- To determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of
PEP07 monotherapy.

Participants will receive PEP07 administered orally once daily (QD) for 2 consecutive days
and 5 days off, every week for 4 weeks until disease progression, intolerable toxicity,
confirmed pregnancy, death, consent withdrawal, HSCT or other anti-cancer treatment is
required, or the Sponsor ends the study, whichever occurs first.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05659732
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Hsin-An Hou, M.D.
Address 0 0
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Brian Shen
Address 0 0
Country 0 0
Phone 0 0
+886 2 2515-8228
Fax 0 0
Email 0 0
brian.shen@pharmaengine.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05659732