Urothelial CarcinomaPhase 1/2NCT05086666
A Phase 1b/2 Clinical Study to Evaluate the Safety and Tolerability and Efficacy of AZD4547
A Phase 1/2 study testing AZD4547 in people with Urothelial Carcinoma, run by Abbisko Therapeutics Co, Ltd at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 25 years and older
- Conditions the study is for
- Urothelial Carcinoma
- What is being tested?
- AZD4547
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 108 participants
- Where
- 1 siteChina
- Study dates
- 3 Jun 2021to 27 May 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Fudan University Cancer Hospital
Shanghai, Shanghai Municipality, 200032
dingwei ye, PhD, 021-64175590-81807, dwyeli@163.com
About this study
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
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.
Read the 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.
- Conditions
- Urothelial Carcinoma
- Being tested
- AZD4547
- Keywords
- urothelial carcinoma, FGFR2/3
- Medical subject headings
- Carcinoma, Transitional Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD4547Drug
Also called ABSK091
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.
| Study group | Role | What they receive |
|---|---|---|
| Urothelial Carcinoma with FGFR2/3 Gene Alterations | Experimental | Evaluate the Efficacy of AZD4547 in Urothelial Carcinoma Patients with FGFR2/3 Gene Alterations Receives: Drug: AZD4547 |
What is being measured
The primary outcome is the main question the study is designed to answer.
DLT
Incidence of dose limiting toxicity (DLT)
Measured: 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) .
Measured: 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
Measured: 6 months
Secondary outcomes (3)
DOR
Duration of response (DoR): The time from the first evaluation of [CR] or [PR] until disease progression;
Measured: at least 6 months
DCR
Disease control rate (DCR): DCR = [CR] + [PR] + stable disease [SD];
Measured: at least 6 months
PFS
Progression-free survival (PFS): time to progression or death from the first day subjects receive AZD4547;
Measured: at least 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2021
- Study start3 Jun 2021
- Primary completion14 Aug 2023 (estimated)
- Study completion27 May 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Urothelial CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 108 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Abbisko Therapeutics Co, Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- yuan lu, PhD, Study director, Abbisko Therapeutics Co, Ltd
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05086666
- Sponsor's protocol ID
- ABSK091-201
- Status last verified
- Jun 2021
- First submitted
- 9 Oct 2021
- Last updated
- 21 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05086666
- Acronym / sponsor ID
- ABSK091-201
- Conditions
- Urothelial Carcinoma
- Keywords
- urothelial carcinoma, FGFR2/3
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 108 participants (estimated)
- Lead sponsor
- Abbisko Therapeutics Co, LtdIndustry (pharma, biotech, devices)
- Study start
- 3 Jun 2021 (actual)
- Primary completion
- 14 Aug 2023 (estimated)
- Study completion
- 27 May 2024 (estimated)
- First posted
- 21 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Urothelial Carcinoma with FGFR2/3 Gene Alterations | Experimental | Drug: AZD4547Evaluate the Efficacy of AZD4547 in Urothelial Carcinoma Patients with FGFR2/3 Gene Alterations |
Who may qualify
- Ages
- 25 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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):
Key exclusion criteria (15 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD4547Also: ABSK091In 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. | Drug | Urothelial Carcinoma with FGFR2/3 Gene Alterations |
Primary outcome
DLT
Time frame: 21 days
Incidence of dose limiting toxicity (DLT)
AEs and SAEs
Time frame: at least 6 months
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) .
ORR
Time frame: 6 months
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
3 secondary outcomes
DOR
Time frame: at least 6 months
DCR
Time frame: at least 6 months
PFS
Time frame: at least 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
yuan lu, PhD study director
Abbisko Therapeutics Co, Ltd
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AZD4547 in people with Urothelial Carcinoma, run by Abbisko Therapeutics Co, Ltd at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact yuan yuan (+86-021-68912098, yuan.lu@abbisko.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DLT (time frame: 21 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2021.