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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/NCT04434482




Registration number
NCT04434482
Ethics application status
Date submitted
14/06/2020
Date registered
17/06/2020
Date last updated
29/09/2023

Titles & IDs
Public title
IMP4297 in Combination With Temozolomide in Patients With Advanced Solid Tumors and Small Cell Lung Cancer
Scientific title
A Phase Ib/II, Open-Label, Multi-Center, Dose Escalation and Expansion Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of IMP4297 in Combination With Temozolomide in Patients With Advanced Solid Tumors and Small Cell Lung Cancer
Secondary ID [1] 0 0
IMP4297-106
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumours 0 0
Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - IMP4297(senaparib)

Experimental: IMP4297(senaparib) and temozolomide - IMP4297 and temozolomide


Treatment: Drugs: IMP4297(senaparib)
The dose levels will be escalated following a modified 3+3 dose escalation scheme.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part I: Dose Escalation safety and tolerability
Timepoint [1] 0 0
From signing ICF until safety follow-up
Primary outcome [2] 0 0
Part I: Dose Escalation MTD
Timepoint [2] 0 0
from the initiation of study drugs until the end of dose escalation phase(approximately 1 year)
Primary outcome [3] 0 0
Part I: Dose Escalation RP2D
Timepoint [3] 0 0
from the initiation of study drugs until the end of dose escalation phase(approximately 1 year)
Primary outcome [4] 0 0
Part II: Dose Expansion Overall Response Rate (ORR)
Timepoint [4] 0 0
from the initiation of study drugs until documented disease progression, withdrawal of consent, loss to follow-up, death, initiation of new anti-cancer treatment or termination of study, which occurs first.
Secondary outcome [1] 0 0
Part I: Dose Escalation plasma PK profile of IMP4297 and temozolomide
Timepoint [1] 0 0
Cycle 1 Day 1, Cycle 1 Day 15,Cycle 2 Day 1,Any cycle after cycle 2,unscheduled visit
Secondary outcome [2] 0 0
Part I: Dose Escalation anti-tumor activity
Timepoint [2] 0 0
from the initiation of study drugs until documented disease progression, withdrawal of consent, loss to follow-up, death, initiation of new anti-cancer treatment or termination of study
Secondary outcome [3] 0 0
Part I: Dose Escalation,effect of IMP4297 on QT interval
Timepoint [3] 0 0
Cycle 1 Day 1,Cycle 1 Day 15,Cycle 2 Day 1,CnD1,EOT, unscheduled visit
Secondary outcome [4] 0 0
Part II: Dose Expansion safety and tolerability
Timepoint [4] 0 0
From signing ICF until safety follow-up
Secondary outcome [5] 0 0
Part II: Dose Expansion anti-tumor activity
Timepoint [5] 0 0
from the initiation of study drugs until documented disease progression, withdrawal of consent, loss to follow-up, death, initiation of new anti-cancer treatment or termination of study
Secondary outcome [6] 0 0
Part II: Dose Expansion PK profile of IMP4297 and temozolomide
Timepoint [6] 0 0
Cycle 1 Day 1,Cycle 1 Day 15,Cycle 2 Day 1,Any cycle after cycle 2,unscheduled visit
Secondary outcome [7] 0 0
Part II: Dose Expansion effect of IMP4297 on QT interval
Timepoint [7] 0 0
Cycle 1 Day 1,Cycle 1 Day 15,Cycle 2 Day 1,CnD1,EOT, unscheduled visit

Eligibility
Key inclusion criteria
1. The patient must voluntarily participate in this clinical study and be willing and
able to provide written informed consent/assent for the trial.

2. Age = 18 years old on the day of signing informed consent form (ICF), males or females

3. Patient population:

1. In Part I: The patient must have histologically or cytologically confirmed
advanced solid tumor that is refractory to standard treatment or for which no
standard treatment exists, including but not limited to triple-negative breast
cancer (TNBC), SCLC, ovarian cancer (OC) and metastatic castration-resistant
prostate cancer (mCRPC).

2. In Part II: The patients must be histologically or cytologically confirmed
ES-SCLC with disease progression after one and only one course of 1L standard
platinum-based therapy. Anti-PD-1 or anti-PD-L1 antibody therapy is acceptable as
long as it's part of the 1L treatment. Including platinum sensitive and platinum
resistant patients. Platinum sensitive is defined as the relapse-free interval
exceeds 90 days after treatment with platinum doublets is completed; The platinum
resistant represents disease relapses within 90 days of treatment completion
during a chemotherapy-free interval (CFI).

3. In Part I: Patients have an ECOG performance status of 0 to 1.

4. In Part II: Patients have an ECOG performance status of 0 to 2.

5. Patients have a life expectancy of =12 weeks.

6. In Part II: patients have at least 1 measurable lesion per RECIST v1.1, including
a previously irradiated lesion if has progressed since radiotherapy, that can be
accurately measured at baseline which is suitable for accurate repeated
measurements

4. Patients have adequate organ function, as indicated by the following laboratory values
(had not received blood transfusion, apheresis infusion, erythropoietin, granulocyte
colony-stimulating factor, and other relevant medical support within 28 days before
the administration of the IPs

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

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

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

- For those with childbearing potential, they should have a negative serum
pregnancy test during the screening period (within 7 days prior to the first dose
of the IPs), should not be in lactation, and willing to take effective
contraceptive measures throughout the study period, from study entry up to 6
months after the last dose of the IP(s).

6. Male patients are eligible to participate in the study if they have undergone
vasectomy or agree to use effective methods of contraception from study entry up to 6
months after the last dose of the IP(s).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients with primary tumor in central nervous system (CNS) and active or untreated
central CNS metastases and/or carcinomatous meningitis should be excluded. Patients
with previously treated brain metastases may participate provided they are clinically
stable for at least 4 weeks and, have no evidence of new or enlarging brain metastases
and no requirements for corticosteroids 14 days prior to dosing with IPs.

2. Patients with serious acute and chronic infections, including:

- Patients with an uncontrolled acute infection, or an active infection requiring
systemic treatment, or patients who have received systemic antibiotics within 2
weeks prior to the first dose of the IPs; prophylaxis use of systemic antibiotics
treatment for upper tract infection is allowed as long as no violation with the
requirement in Section 6.5 Concomitant Therapy.

- Patients who have 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/uL are ineligible for enrollment. Patients with unknown HIV infection
status who are unwilling to undergo HIV testing should not be enrolled in the
study;

- Patients who have 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 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 in the study centers is
higher than 2500 copies [cps]/mL or 500 IU/mL, the patients in the study center
with an HBV DNA assay result lower than the lower detection limit of the assay
can be enrolled.

- Active tuberculosis

3. Patients who have previously received PARP inhibitors.

4. Patients who have received strong CYP3A4 inhibitors or inducers prior to the first
dose of the IPs (the patient can be enrolled if the elution period prior to the first
dose of the IPs is =5 half-lives), or patients who need to continue receiving these
medications during the study period.

5. Patients who have received a live-virus vaccination within 28 days of the planned
start of study.

6. Patients who have participated a study of an investigational agent and received study
therapy or used an investigational device within 28 days of the first dose of
treatment.

7. Patients have not recovered (i.e., to =Grade 1 or to baseline, as evaluated by
NCI-CTCAE v5.0) from cytotoxic therapy-induced AEs, except for alopecia.

8. Patients who have received anti-cancer chemotherapy, endocrine therapy,
herbal/alternative therapies (including Chinese herbal or Chinese medicine or
proprietary Chinese medicine), or other anti-cancer systemic treatment (except
anti-cancer antibody) within 5 half-lives or 14 days, whichever is longer prior to the
first dose of the IPs. Patients who have received anti-cancer antibody within 28 days
prior to the first dose of the IPs.

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

10. In Part II of the study, patients who have other malignancies within 2 years prior to
the first dose of the IPs will be excluded. except for radically treated locally
curable malignant tumors, such as basal or squamous cell skin cancer, superficial
bladder cancer, or prostate, cervical or breast carcinoma in situ.

11. Patients with uncontrolled pleural effusion, pericardial effusion or ascites requiring
recurrent drainage procedures (once monthly or more frequently). Please contact
medical monitor if any further discussion or clarification is needed.

12. Patients with a history of seizures.

13. Patients with a previously documented diagnosis of myelodysplastic syndrome (MDS).

14. Patients who have major cardiovascular diseases (such as congestive heart failure,
unstable angina, atrial fibrillation, arrhythmia); patients who have acute myocardial
infarction, unstable angina, stroke, or transient ischemic attack within 6 months
prior to the first dose of the IPs; patients who have congestive heart failure (=New
York Heart Association [NYHA] Classification Class II); patients who have severe
arrhythmia requiring medication (including QT interval [QTc] prolongation corrected by
the Fridericia's formula [QTcF] of more than 480 msec, pacemaker installation, and
previous diagnosis of congenital long QT syndrome).

15. Patients who are unable to swallow capsules. Patients have gastrointestinal illnesses
that may affect the absorption of oral medication IMP4297 and temozolomide.

16. Patients with a known hypersensitivity to IMP4297, temozolomide or any of the
excipients of the products.

17. Patients who have received transplantation including patients with previous allogeneic
bone marrow transplant.

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

19. The investigator believes that the patient's underlying disease may put the patient at
risk in IP administration or may affect the evaluation of toxicity events or AEs.

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/Phase 2
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
7/08/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2025
Actual
Sample size
Target
113
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Border Medical Oncology - Albury
Recruitment hospital [2] 0 0
Blacktown Hospital - Blacktown
Recruitment hospital [3] 0 0
Orange Hospital - Orange
Recruitment hospital [4] 0 0
Peninsula Health Frankston Hospital - Frankston
Recruitment postcode(s) [1] 0 0
2640 - Albury
Recruitment postcode(s) [2] 0 0
2148 - Blacktown
Recruitment postcode(s) [3] 0 0
2800 - Orange
Recruitment postcode(s) [4] 0 0
3199 - Frankston
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Illinois
Country [2] 0 0
United States of America
State/province [2] 0 0
Ohio
Country [3] 0 0
United States of America
State/province [3] 0 0
Tennessee
Country [4] 0 0
China
State/province [4] 0 0
Beijing
Country [5] 0 0
China
State/province [5] 0 0
Jilin
Country [6] 0 0
China
State/province [6] 0 0
Shanghai
Country [7] 0 0
China
State/province [7] 0 0
Wuhan
Country [8] 0 0
Korea, Republic of
State/province [8] 0 0
Cheongju-si
Country [9] 0 0
Korea, Republic of
State/province [9] 0 0
Gyeonggi-do
Country [10] 0 0
Korea, Republic of
State/province [10] 0 0
Seoul
Country [11] 0 0
Taiwan
State/province [11] 0 0
Taichung
Country [12] 0 0
Taiwan
State/province [12] 0 0
Tainan
Country [13] 0 0
Taiwan
State/province [13] 0 0
Taipei
Country [14] 0 0
Taiwan
State/province [14] 0 0
Taoyuan

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

Ethics approval
Ethics application status

Summary
Brief summary
This is an open-label, multi-center, dose-escalation and dose-expansion phase I study to
evaluate the safety, tolerability, PK characteristics and anti-tumor activity of PARP
inhibitor IMP4297 and temozolomide combination therapy in patients with advanced solid tumors
and with ES-SCLC who develops disease progression after 1L platinum-based regimen.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04434482
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
Min Song
Address 0 0
Country 0 0
Phone 0 0
021 68411121
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04434482