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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/NCT04964375




Registration number
NCT04964375
Ethics application status
Date submitted
24/06/2021
Date registered
16/07/2021
Date last updated
27/04/2022

Titles & IDs
Public title
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Scientific title
A Phase 1, Open-Label Study of ABSK043 to Assess Safety, Tolerability, and Pharmacokinetics in Patients With Advanced Solid Tumor
Secondary ID [1] 0 0
ABSK043-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasms 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ABSK043 oral capsule

Experimental: ABSK043 - Dose escalation of oral ABSK043 with a starting dose of 200mg once daily will be guided by"BOIN" escalation rules based on safety data until an MTD has been identified or a RDE. For each dose,In the escalation part, sequential cohorts of patients will receive an oral dose of ABSK043 in repeated 28-day cycles. Starting dose level will be 200 mg QD. Cohort 3 on 800mg will be switched to 400mg BID.Then, patients will continuously receive ABSK043 (total daily dose) in repeated 28-day cycles.For the Dose Expansion Phase, patients will each receive orally administered doses of ABSK043 at the RDE in repeated 28-day cycles.


Treatment: Drugs: ABSK043 oral capsule
ABSK043 is a novel, oral small molecule inhibitor of PD-L1
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
DLT
Timepoint [1] 0 0
At the end of Cycle 1 (each cycle is 28 days)
Primary outcome [2] 0 0
Incidence and Severity of AEs
Timepoint [2] 0 0
Through study completion, an average of 6 months
Secondary outcome [1] 0 0
PFS
Timepoint [1] 0 0
throughout study completion, on average of half year
Secondary outcome [2] 0 0
DCR
Timepoint [2] 0 0
throughout study completion, on average of half year
Secondary outcome [3] 0 0
DOR
Timepoint [3] 0 0
throughout study completion, on average of half year
Secondary outcome [4] 0 0
Cmax
Timepoint [4] 0 0
at the end of Cycle 1 Day15 (each cycle is 28 days)
Secondary outcome [5] 0 0
Tmax
Timepoint [5] 0 0
at the end of Cycle 1 Day15 (each cycle is 28 days)
Secondary outcome [6] 0 0
AUC
Timepoint [6] 0 0
at the end of Cycle 1 Day15 (each cycle is 28 days)
Secondary outcome [7] 0 0
t1/2
Timepoint [7] 0 0
at the end of Cycle 1 Day15 (each cycle is 28 days)
Secondary outcome [8] 0 0
Vz/F
Timepoint [8] 0 0
at the end of Cycle 1 Day15 (each cycle is 28 days)
Secondary outcome [9] 0 0
CL/F
Timepoint [9] 0 0
at the end of Cycle 1 Day15 (each cycle is 28 days)
Secondary outcome [10] 0 0
Css_max
Timepoint [10] 0 0
at the end of Cycle 1 Day15 (each cycle is 28 days)
Secondary outcome [11] 0 0
Css_min
Timepoint [11] 0 0
at the end of Cycle 1 Day15 (each cycle is 28 days)
Secondary outcome [12] 0 0
AUCss
Timepoint [12] 0 0
at the end of Cycle 1 Day15 (each cycle is 28 days)
Secondary outcome [13] 0 0
Rac
Timepoint [13] 0 0
at the end of Cycle 1 Day15 (each cycle is 28 days)
Secondary outcome [14] 0 0
ORR
Timepoint [14] 0 0
throughout study completion, on average of half year

Eligibility
Key inclusion criteria
1. Patient should understand, sign, and date the written voluntary informed consent form
prior to screening.

2. Male or female aged 18 years or older (or other age range required by local
regulations or IRB).

3. For Escalation part: patients must have histologically confirmed solid tumors that
have progressed on or intolerance to standard therapy or whom no standard therapy
exists or whom refuse to receive standard therapy;

For Expansion Part:

1. Melanoma cohort: Patients must have histologically confirmed melanoma that have have
progressed on or intolerance to standard therapy(including immune-checkpoint
inhibitors) or whom no standard therapy exists or whom refuses to receive standard
therapy

2. MSI-H/dMMR cohort: Patients must have histologically confirmed solid tumors harboring
MSI-H or dMMR that have progressed on or intolerance to standard therapy or whom no
standard therapy exists or whom refuses to receive standard therapy.

3. Patients must have at least one measurable target lesion according to RECIST 1.1.

4. Patients are willing to receive biopsy. 4. ECOG performance status 0 or 1 5. Life
expectancy =3 months 6. Adequate organ function and bone marrow function as indicated
by the following screening assessments performed within 14 days prior to the first
dose of study drug:

1. Absolute neutrophil count (ANC) =1.5×109/L

2. Platelet count (PLT) =75×109/L without transfusions within 14 days before 1st
dose

3. Hemoglobin (Hb) =90 g/L

4. Total bilirubin (TBIL) =1.5×ULN

5. Aspartate transaminase (AST)/alanine transaminase (ALT), =3×ULN (=5 × ULN in the
presence of hepatic metastases).

6. Serum creatinine (Cr) of =1.5×ULN for the reference laboratory or creatinine
clearance (Crcl) =50 mL/min based either on urine collection or Cockcroft-Gault
estimation
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Known allergy or hypersensitivity to any component of the investigational product.

2. For expansion part MSI-H or dMMR cohort only: previously treated with PD-(L)1 pathway
inhibitors (including monoclonal antibody and small molecular agents).

3. History of autoimmune disease, including but not limited to myasthenia gravis,
myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis,
inflammatory bowel disease, vascular thrombosis associated with antiphospholipid
syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome,
multiple sclerosis, vasculitis, or glomerulonephritis, etc.

4. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced
pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic
organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan,
history of radiation pneumonitis in the radiation field (fibrosis) is permitted.

5. For expansion part only: Has a known additional malignancy that is progressing or
required active treatment. Exceptions include basal cell carcinoma of the skin,
squamous cell carcinoma of the skin that has undergone potentially curative therapy,
or other in situ cancers.

6. Inability to take oral medication or significant nausea and vomiting, malabsorption,
external biliary shunt, or significant bowel resection that would preclude adequate
absorption of oral medication.

7. Previous anti-cancer therapy, including chemotherapy (chemotherapy with nitrosourea or
mitomycin should be 6 weeks prior to initiation of study treatment), radiotherapy,
molecular targeted therapy or other investigational drugs received in previous
clinical trial =4 weeks; endocrine therapy =2 weeks or =5-half-life (whichever is
shorter) prior to initiation of study treatment.

8. Major surgery within 4 weeks of the first dose of study drug and all surgical wounds
must be healed and free of infection or dehiscence.

9. Vaccination with a live, attenuated vaccine within 4 weeks of the first dose of study
treatment and while on trial is prohibited except for administration of inactivate
vaccines (e.g., COVID-19 vaccines, inactivated influenza vaccines).

10. Prior toxicities from chemotherapy, radiotherapy, and other anti-cancer therapies,
including immunotherapy that have not regressed to Grade =1 severity (CTCAE v5.0) with
the exception of alopecia, vitiligo or event(s) that is considered non-clinical
meaningful by the Investigator.

11. History of Grade =3 immune-related adverse event(s) occurred in previous treatment.

12. Treatment with systemic corticosteroids or other systemic immunosuppressive
medications (including but not limited to prednisone, dexamethasone, cyclophosphamide,
azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within
2 weeks prior to randomization, or anticipated requirement for systemic
immunosuppressive medications during the trial (patients who have received acute,
low-dose, systemic immunosuppressant medications (e.g., a one-time dose of
dexamethasone for nausea) may be enrolled in the study; patients with a history of
allergic reaction to IV contrast requiring steroid pre-treatment should have baseline
and subsequent tumor assessments performed using MRI; the use of inhaled
corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids (e.g.,
fludrocortisone) for patients with orthostatic hypotension, and low-dose supplemental
corticosteroids for adrenocortical insufficiency are allowed.

13. For expansion part only: last treatment with therapeutic oral or intravenous
antibiotics within 2 weeks prior to first dose of study treatment.

14. Concomitant use of the drugs/remedies that may cause pharmacokinetic drug-drug
interactions; Consumption of grapefruit juice, grapefruit hybrids, pomegranates,
starfruit, pomelos, Seville oranges or juice or products within 7 days prior to the
first dose of study medication (for Escalation Part only).

15. Active central nervous system (CNS) metastases including cerebral edema, system
hormone treatment, disease progression due to intracranial lesions, leptomeningeal
metastasis, and other clinical symptoms related to CNS metastases (if stable disease>8
weeks after treatment and free from glucocorticoids can be enrolled).

16. Impaired cardiac function or clinically significant cardiac disease, including any one
of the following:

- New York Heart Association class III or IV heart disease, active ischemia or any
other uncontrolled cardiac condition such as angina pectoris, clinically
significant cardiacarrhythmia requiring therapy, uncontrolled hypertension or
congestive heart failure.

- Baseline prolongation of the rate-corrected QT interval based on repeated
demonstration of QTcF >480 ms or history of long QT interval corrected (QTc)
syndrome (Note: QTc interval corrected by Fridericia's formula). Left ventricular
ejection fraction (LVEF) <50% or below the lower limit of normal(whichever is
higher)

17. Known human immunodeficiency virus or active hepatitis B, or active hepatitis C
infection or active tuberculosis. Positive tests for hepatitis B virus surface antigen
(HBsAg), or antibody to hepatitis B core Ag or hepatitis C RNA in serum. (subjects
with history of hepatitis C infection but negative hepatitis C virus polymerase chain
reaction (PCR) test and subjects with hepatitis B with positive hepatitis B surface
antibody are allowed)

18. Patients with refractory/uncontrolled ascites or pleural effusion. Patients with
indwelling catheters are allowed.

19. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
female after conception and until the termination of gestation, confirmed by a
positive human chorionic gonadotropin (hCG) laboratory test within 7 days prior to the
start of study drug.

20. Non-surgically sterilized male or female patients of childbearing potential must agree
to use effective methods of birth control during the study and for up to 6 months
after the last dose of study drug.

21. Sexually active males unless they use a condom during intercourse while taking drug
and for 5 compound half-lives plus 60 days after stopping study drug and should not
father a child in this period. A condom is required to be used also by vasectomized
men in order to prevent delivery of the drug via seminal fluid.

22. Any other clinically significant comorbidities, such as uncontrolled pulmonary
disease, active infection, or any other condition, which in the judgment of the
Investigator, could compromise compliance with the protocol, interfere with the
interpretation of study results, or predispose the patient to safety risks.

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
Unknown status
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/08/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
23/03/2023
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Icon Cancer Centre South Brisbane - Brisbane
Recruitment hospital [2] 0 0
Peninsula & South Eastern Haematology and Oncology Group - Frankston
Recruitment hospital [3] 0 0
Sydney South West Private Hospital - Liverpool
Recruitment postcode(s) [1] 0 0
4101 - Brisbane
Recruitment postcode(s) [2] 0 0
- Frankston
Recruitment postcode(s) [3] 0 0
- Liverpool

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Abbisko Therapeutics Co, Ltd
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase 1, Open-Label Study of ABSK043 to Assess Safety, Tolerability, and
Pharmacokinetics in Patients with Advanced Solid Tumor.

Preliminary antitumor activity will also be assessed. Investigate the pharmacodynamics (PD)
effects and Investigate the metabolites of oral ABSK043
Trial website
https://clinicaltrials.gov/ct2/show/NCT04964375
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jermaine Coward
Address 0 0
Icon Cancer Centre South Brisbane
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Ming Zhang
Address 0 0
Country 0 0
Phone 0 0
+86-21-68912098
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/NCT04964375