A Phase 1b/2 Clinical Study to Evaluate the Safety and Tolerability and Efficacy of AZD4547

NCT05086666 | Unknown Phase 1

• 1 other identifier: ABSK091-201
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

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.

Conditions

Urothelial Carcinoma

Keywords

urothelial carcinoma; FGFR2/3

Outcome Measures

Primary Outcomes (3)

• DLT

  Incidence of dose limiting toxicity (DLT)

  21 days

• AEs and SAEs

  Incidence and grade of adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESI) (based on Common Terminology Criteria for Adverse Events, CTCAE 5.0) .

  at least 6 months

• ORR

  To confirm objective response rate (assessed by RECIST 1.1) in FGFR2/3 gene altered (including mutations and/or fusions) subjects with locally advanced or metastatic urothelial cancer with treated with AZD4547

  6 months

Secondary Outcomes (3)

• DOR

  at least 6 months

• DCR

  at least 6 months

• PFS

  at least 6 months

Study Arms (1)

Urothelial Carcinoma with FGFR2/3 Gene Alterations

EXPERIMENTAL

Evaluate the Efficacy of AZD4547 in Urothelial Carcinoma Patients with FGFR2/3 Gene Alterations

Drug: AZD4547

Interventions

AZD4547 DRUG

In Phase 1b study, subjects will receive continuous twice daily dosing in 21-day cycles (no matter if missed doses or delays exist), with pre-set dose cohorts of 80 mg BID and 120 mg BID. In Phase 2, subjects will receive continuous twice daily dosing in 21-day cycles with the RP2D or other doses as determined by the investigator and sponsor.

Also known as: ABSK091

Urothelial Carcinoma with FGFR2/3 Gene Alterations

Eligibility Criteria

• Age: 25 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged ≥ 25, both male and female;
• 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)
• ECOG PS (performance status) score of 0-2;
• Expected survival of ≥ 3 months;
• 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):
• 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;
• Subjects must voluntarily participate in this clinical trial, understand the study procedures and be able to sign an informed consent form in writing.

You may not qualify if:

• Known to be allergic to AZD4547 tablets or constituents;
• 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);
• 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);
• 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;
• 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;
• 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;
• 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.);
• There is a persistent increase in serum phosphorus levels (\> ULN) requiring treatment control within 14 d prior to the first dose for study treatment;
• 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);
• There are uncontrolled cardiovascular diseases or a history thereof
• 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;
• There are severe untreated skin/mucosal ulcers, chronic ulcers of the lower extremities, known gastric ulcers or incisions;
• 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);
• There are any abnormal corneal or retinal changes during screening that may increase the risk of ocular toxicity
• 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.

Sponsors & Collaborators

• Abbisko Therapeutics Co, Ltd: lead

Study Sites (1)

Fudan University Cancer Hospital

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

AZD4547

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• yuan lu, PhD

  Abbisko Therapeutics Co, Ltd

  STUDY DIRECTOR

Central Study Contacts

yuan yuan

CONTACT

+86-021-68912098; yuan.lu@abbisko.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2021
• First Posted: October 21, 2021
• Study Start: June 3, 2021
• Primary Completion: August 14, 2023
• Study Completion: May 27, 2024
• Last Updated: October 21, 2021

Record last verified: 2021-06

Locations

CN (1)