Trial Review

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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/NCT05269316




Registration number
NCT05269316
Ethics application status
Date submitted
11/02/2022
Date registered
7/03/2022
Date last updated
13/10/2023

Titles & IDs
Public title
Study to Evaluate IMP9064 as a Monotherapy or in Combination in Patients With Advanced Solid Tumors
Scientific title
A First-in-human, Phase 1/2, Open-label, Multi-center, Dose-escalation and Dose-expansion Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of the ATR Inhibitor IMP9064 Monotherapy and in Combination With PARP Inhibitor Senaparib in Patients With Advanced Solid Tumors
Secondary ID [1] 0 0
IMP9064-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumor 0 0
Advanced Solid Tumor 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - IMP9064

Experimental: IMP9064 Monotherapy - Dose-escalation IMP9064 administered orally on empty stomach once/twice daily


Treatment: Drugs: IMP9064
IMP9064 Monotherapy administered for 21 days
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of adverse events (Safety and Tolerability)
Timepoint [1] 0 0
11 months
Primary outcome [2] 0 0
To determine the Maximum Tolerable Dose
Timepoint [2] 0 0
11 months
Secondary outcome [1] 0 0
To determine Maximum concentration (Cmax)
Timepoint [1] 0 0
11 months
Secondary outcome [2] 0 0
To determine area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-t)
Timepoint [2] 0 0
11 months
Secondary outcome [3] 0 0
To assess Overall response rate (ORR)
Timepoint [3] 0 0
11 months
Secondary outcome [4] 0 0
To assess Disease control rate (DCR)
Timepoint [4] 0 0
11 months
Secondary outcome [5] 0 0
To assess Duration of response(DOR)
Timepoint [5] 0 0
11 months
Secondary outcome [6] 0 0
To assess Progression free survival(PFS)
Timepoint [6] 0 0
11 months
Secondary outcome [7] 0 0
To assess Overall survival(OS)
Timepoint [7] 0 0
11 months
Secondary outcome [8] 0 0
To assess QT interval
Timepoint [8] 0 0
11 months

Eligibility
Key inclusion criteria
1. Patients = 18 years of age on the day of signing informed consent form (ICF) (at the
time of screening for Part 1 and Part 2C and pre-screening for Part 2A and Part 2B).

2. Must voluntarily participate in the study and be willing and able to provide signed
informed consent which includes compliance with the requirements and restrictions
listed in the ICF and in this protocol.

3. Male or female patients with histologically or cytologically confirmed AST refractory
to or intolerant of available standard-of-care therapy or for which no standard
treatment exists.

4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 (Part 1) at
screening.

5. Provision of tumor tissue samples.

6. Life expectancy = 12 weeks (according to Investigator's judgement).

7. Female patients should meet at least 1 of the following criteria before they can
participate in the study:

1. Females who have no childbearing potential (i.e. physiologically incapable of
pregnancy), including those who have undergone hysterectomy, bilateral
oophorectomy, or bilateral salpingectomy.

2. Post-menopausal (total cessation of menses for = 1 year).

3. Females of childbearing potential should have a negative serum pregnancy test
during the screening period (within 7 days prior to the first dose of the study
drug), should not be in lactation, and should be willing to practice a highly
effective contraceptive method throughout the study period (from study entry up
to 6 months after the last dose of the study drug). A highly effective method of
contraception is defined as one that results in a low failure rate, i.e., less
than 1% per year, when used consistently and correctly (See Appendix 4, Section
11.4).

8. Male patients are eligible to participate in the study if they have undergone
vasectomy or agree to use a highly effective method of contraception and refrain from
donating sperms from study entry up to 6 months after the last dose of the study drug.

9. Willing and able to comply with study visits and study-related procedures.

10. For optional PD analysis in Part 1, patients should be willing provide hairs plucked
from eyebrows pre and post treatment with IMP9064 and fresh tumor biopsies (if deemed
necessary by SMC) pre and post treatment with IMP9064.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Known history of hypersensitivity to any components of the study drug.

2. Any investigational or approved systemic cancer therapy (including chemotherapy,
immunotherapy, hormonal therapy and herbal/alternative therapies with anti-cancer
indications, or targeted therapy) administered within 28 days or 5 half-lives,
whichever is shorter, before the first dose of study drug.

3. Any previous treatment-related toxicities have not recovered, i.e. to = Grade 1, as
evaluated by NCI-CTCAE version 5.0 or baseline, except alopecia and anemia. Patients
with chronic Grade 2 toxicities which are well managed and stable may be eligible per
the discretion of the investigator after the discussion with the Sponsor and medical
monitor, e.g., Grade 2 chemotherapy-induced neuropathy.

4. Primary tumor in CNS, or active or untreated CNS metastases and/or carcinomatous
meningitis. Patients with previously treated brain metastases may participate provided
they are clinically stable for at least 28 days and have no evidence of new or
enlarging brain metastases and no requirements for high-dose corticosteroids 14 days
prior to dosing with study drug. Patients on low dose corticosteroids (< 20 mg
prednisone or equivalent per day) may participate.

5. Clinically significant cardiovascular condition, including:

- History of congestive heart failure (New York Heart Association [NYHA] Class > 2)

- History of unstable angina

- New-onset angina or myocardial infarction within the 6 months prior to the first
dose of study drug

- New onset of atrial fibrillation, supraventricular arrhythmia, or ventricular
arrhythmia within the 6 months prior to the first dose of study drug and
requiring treatment or intervention. History of atrial fibrillation,
supraventricular arrhythmia, or ventricular arrhythmia will be allowed provided
the condition is stably controlled.

6. History or presence of an abnormal ECG that, in the Investigator's opinion, is
clinically meaningful (including QTcF > 470 msec for females, QTcF > 450 msec for
males by Fridericia formula at screening, pacemaker installation or previous diagnosis
of congenital long QT syndrome).

7. Patients who have undergone a major surgery or have undergone a radical radiotherapy
within 28 days prior to the first dose of study drug or have undergone a palliative
radiotherapy within 14 days prior to the first dose of study drug, or have used a
radioactive drug (Strontium, Samarium, etc.) within 56 days prior to first dose of
study drug.

8. Patients with infections, including:

- An uncontrolled acute infection, or an active infection requiring systemic
treatment, or patients who have received systemic antibiotics within 14 days
prior to the first dose of the study drug; prophylaxis use of systemic
antibiotics treatment for upper tract infection is allowed as long as there is no
violation with the requirement of concomitant medications.

- A known history of human immunodeficiency virus (HIV) infection and/or acquired
immunodeficiency syndrome or positive HIV testing should undergo CD4+ T-cell test
during the screening period. Patients with CD4+ T-cell counts < 350 cells/µL are
ineligible for enrolment as well as patients with unknown HIV infection status
who are unwilling to undergo HIV testing.

- A known active hepatitis B or C. To be included in the study, patients with
hepatitis B virus surface antigen (HBsAg) or hepatitis C virus (HCV) antibody
positive test results during screening must be further tested for hepatitis B
virus (HBV) DNA titer (excluding patients with a DNA titer of more than 2500
copies [cps]/mL or 500 IU/mL) and HCV ribonucleic acid (RNA) (excluding patients
with an HCV RNA concentration exceeding the lower detection limit of the assay)
to exclude active hepatitis B or hepatitis C infection requiring treatment.
Hepatitis B virus carriers, patients with stable hepatitis B infection after drug
treatment (DNA titer not exceeding 2500 copies [cps]/mL or 500 IU/mL) and
hepatitis C infected patients who received treatment and achieved sustained
virologic response for at least 12 weeks can be enrolled. Note: If the lower
detection limit of the HBV DNA assay is higher than 2500 copies [cps]/mL or 500
IU/mL, the patients with an HBV DNA assay result lower than the lower detection
limit of the assay can be enrolled.

- Active tuberculosis.

9. Positive test result for severe acute respiratory syndrome-related coronavirus
(SARS-CoV-2) test. SARS-CoV-2 test is mandatory during screening for patients who have
exposure to suspected, probable, or confirmed cases of SARS-CoV-2 infection within 14
days, via a validated test per local guidance; the result should be available within 4
days prior to the first dose of study drug.

10. Any other medical (e.g., Child-Pugh class B or C, pulmonary, metabolic, congenital,
endocrinal or CNS disease, etc.), psychiatric, or social condition deemed by the
Investigator to be likely to interfere with a patient's rights, safety, welfare or
ability to sign informed consent, cooperate and participate in the study, or interfere
with the interpretation of the results.

11. Receipt of:

- Any treatment targeting the ATR/CHK1 pathway.

- Live virus or bacterial vaccine within 28 days prior to the first dose of study
drug and whilst the patient is receiving study drug. Patients who require
COVID-19 vaccination whilst on study drug should receive a non-live vaccine
(e.g., one based on messenger RNA (mRNA) or fully inactivated/genetically
modified viruses incapable of replication) (see Section 6.8.1).

12. Participation in another clinical study with an investigational product administered
in the last 28 days or 5 half-lives (whichever is shorter) prior to the first
administration of study drug.

13. An investigational device within 28 days prior to the first dose of study drug.

14. Patients who may need continuous treatment with proton pump inhibitors or potassium
competitive acid blockers during the study period.

15. Patients who have other malignancies requiring treatment within 2 years prior to the
first dose of study drug will be excluded, except for radically treated locally
curable basal or squamous cell skin cancer and other malignancies that have been
treated with no relapse within 2 years. Presence of other active invasive cancers will
be excluded for Part 2.

16. Patients who are unable to swallow oral medications.

17. Patients who have gastrointestinal illnesses that may affect the absorption of oral
medications.

18. Patients with a previously documented diagnosis of myelodysplastic syndrome (MDS) or
acute myeloid leukemia (AML), or patients who have received transplantation including
patients with previous allogeneic bone marrow transplant.

19. Patients known to have a history of alcoholism or drug abuse.

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
Other
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
11/02/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/07/2025
Actual
Sample size
Target
61
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Blacktown Hospital - Blacktown
Recruitment hospital [2] 0 0
Linear Clinical Research Limited - Nedlands
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New Jersey
Country [2] 0 0
United States of America
State/province [2] 0 0
New York
Country [3] 0 0
United States of America
State/province [3] 0 0
South Carolina
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
China
State/province [5] 0 0
Beijing
Country [6] 0 0
Taiwan
State/province [6] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Impact Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase 1/2, multicenter, open-label study to evaluate the safety and efficacy of
IMP9064 as monotherapy or in combination with PARP inhibitor Senaparib in patients with
advanced solid tumors
Trial website
https://clinicaltrials.gov/ct2/show/NCT05269316
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Xiangna Chen
Address 0 0
Country 0 0
Phone 0 0
+86-021-68411121
Fax 0 0
Email 0 0
xiangna.chen@impacttherapeutics.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05269316