Brief Title
A Phase 1b/2 Clinical Study to Evaluate the Safety and Tolerability and Efficacy of AZD4547
Official Title
A Phase 1b/2 Clinical Study to Evaluate the Safety and Tolerability of AZD4547 in Patients With Solid Tumors and Its Efficacy in Patients With Locally Advanced or Metastatic Urothelial Carcinoma With FGFR2/3 Gene Alterations
Brief Summary
Phase 1b clinical study to evaluate the PK of oral AZD4547 in Chinese patients and RP2D.
Phase 2 study to evaluate the efficacy of AZD4547 in urothelial carcinoma patients with
FGFR2/3 gene alterations.
Detailed Description
This study is an open-label, Phase 1b/2 clinical study. In the Phase 1b study, the safety and
tolerability of AZD4547 in patients with advanced solid tumors will be evaluated, the PK of
oral AZD4547 in Chinese patients and the recommended phase 2 dose (RP2D) will be determined,
and the antitumor activity will be preliminarily assessed. In the Phase 2 study, the efficacy
of AZD4547 at the recommended dose in patients with locally advanced or metastatic urothelial
carcinoma with FGFR2/3 gene alterations (including mutations and/or fusions) will be
evaluated, and the safety, tolerability, and PK of AZD4547 will be further evaluated.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
DLT
Secondary Outcome
DOR
Condition
Urothelial Carcinoma
Intervention
AZD4547
Study Arms / Comparison Groups
Urothelial Carcinoma with FGFR2/3 Gene Alterations
Description: Evaluate the Efficacy of AZD4547 in Urothelial Carcinoma Patients with FGFR2/3 Gene Alterations
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
108
Start Date
June 3, 2021
Completion Date
May 27, 2024
Primary Completion Date
August 14, 2023
Eligibility Criteria
Inclusion Criteria:
1. Aged ≥ 25, both male and female;
2. Patients with histologically confirmed, surgically unresectable locally advanced or
metastatic uroepithelial carcinoma that may be accompanied by other histologic
differentiation (<50% of the total, including adenoid, squamous, or more aggressive
sarcomatoid/micropapillary differentiation)
3. ECOG PS (performance status) score of 0-2;
4. Expected survival of ≥ 3 months;
5. Acceptable organ functions satisfy the following laboratory test requirements, and the
test results should be obtained within 14 d prior to the first dose for study
treatment (no transfusion of blood or blood products within 14 d prior to the blood
test and no correction with bone marrow hematopoietic stimulating factors):
6. Female or male subjects of childbearing potential must agree to take medically
approved measures for contraception during and for 6 months after the end of the study
treatment; female subjects of childbearing potential must have a negative blood β-HCG
test within 7 d prior to first dosing and must be non-lactating;
7. Subjects must voluntarily participate in this clinical trial, understand the study
procedures and be able to sign an informed consent form in writing.
Exclusion Criteria:
1. Known to be allergic to AZD4547 tablets or constituents;
2. Subjects have previously received selective FGFR inhibitors (in the case of
multi-target inhibitors including FGFR, it is required to discuss with the sponsor to
decide whether they can be included);
3. There have been other malignancies requiring treatment in the past 2 years (except for
cured skin cancer, cervical carcinoma in situ, basal cell carcinoma, focal prostate
cancer with a Gleason score of 6, and focal prostate cancer at low risk of recurrence
with a Gleason score of 3+4 and treated for more than 6 months at screening);
4. There are unstable (those who clinically/radiologically stable for at least 4 weeks
prior to signing the ICF and requiring no long-term corticosteroid treatment may be
enrolled) or symptomatic CNS metastases (other than pia mater metastases), or pia
mater metastases of any condition;
5. The investigator determines that there are significant factors influencing oral drug
absorption, such as inability to swallow complete pills, any type of uncontrollable
nausea and vomiting, residual stomach dysfunction after total gastrectomy or subtotal
gastrectomy, short bowel syndrome after small bowel resection, active diarrhea or
irritable bowel syndrome requiring medical attention;
6. Time to the end of prior other antineoplastic therapy from the time of receiving the
first dose of the study drug: < 4 weeks for major surgical operations (allowing
palliative treatment for localized lesions), radiation therapy (> 30% bone marrow
exposure), conventional chemotherapy, targeted therapy, immunotherapy, other
interventional clinical study therapy (< 6 weeks for treatment with nitrosoureas or
mitomycin); < 2 weeks or 5 drug half-lives (whichever is shorter) for endocrine
therapy, herbal or Chinese medicinal preparations with antitumor indications, or
herbal or Chinese medicinal preparations with adjuvant antitumor therapeutic effects;
7. Patients not recovered to ≤ CTCAE Grade 1 from reversible adverse events due to prior
antineoplastic therapy (except for toxicities of no clinical significance such as
alopecia, skin hypopigmentation, etc.);
8. There is a persistent increase in serum phosphorus levels (> ULN) requiring treatment
control within 14 d prior to the first dose for study treatment;
9. Patients are using, or have used, within 14 d prior to the first dose of study
treatment, the following drugs/foods: CYP3A4, 2D6 strong inhibitors or inducers
(including grapefruit juice, grapefruit hybrids, pomegranate, star fruit, pomelo,
Seville oranges and juice or other processed products);
10. There are uncontrolled cardiovascular diseases or a history thereof
11. Patients are taking medications during screening that may cause prolonged QTc interval
or torsades de pointes (see section 5.4.3). Patients should discontinue such drugs for
at least 5 d or 5 half-lives of the drug (whichever is longer) prior to the first dose
for study treatment;
12. There are severe untreated skin/mucosal ulcers, chronic ulcers of the lower
extremities, known gastric ulcers or incisions;
13. There is human immunodeficiency virus (HIV) infection (positive serologic test for HIV
antibodies); active hepatitis B virus (HBV)/hepatitis C virus (HCV) infection
(excluding those with a previous history of hepatitis C but a negative PCR test for
hepatitis C virus during the screening period, or those with only positive hepatitis B
virus surface antibodies on the hepatitis B test, or positive hepatitis B virus
surface antigen but HBV DNA <1000 IU/mL);
14. There are any abnormal corneal or retinal changes during screening that may increase
the risk of ocular toxicity
15. Any other medical (e.g., respiratory, metabolic, infectious, immune, congenital,
endocrine, or central nervous system disorders), psychiatric, or social factors that
may affect the subject's rights, safety, or the subject's ability to sign the informed
consent form, cooperate, participate in the clinical study, or affect the
interpretation of the study results as determined by the investigator.
Gender
All
Ages
25 Years - N/A
Accepts Healthy Volunteers
No
Contacts
yuan lu, PhD, +86-021-68912098, [email protected]
Location Countries
China
Location Countries
China
Administrative Informations
NCT ID
NCT05086666
Organization ID
ABSK091-201
Responsible Party
Sponsor
Study Sponsor
Abbisko Therapeutics Co, Ltd
Study Sponsor
yuan lu, PhD, Study Director, Abbisko Therapeutics Co, Ltd
Verification Date
June 2021