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Urothelial CarcinomaPhase 1/2NCT03676946

A Clinical Study of PD-L1 Antibody ZKAB001（Drug Code） in Locally Advanced and Metastatic Urothelial Carcinoma

A Phase 1/2 study testing ZKAB001 5mg/kg, ZKAB001 10mg/kg and ZKAB001 15mg/kg in people with Urothelial Carcinoma, run by Lee's Pharmaceutical Limited at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This is a Phase 1+2, open-label, dose-escalation, and multidose study, aiming to investigate the safety, tolerability and pharmacokinetics of ZKAB001 (a fully human monoclonal antibody targeting the Programmed Death - Ligand 1 (PD-L1) membrane receptor on T lymphocytes and other cells of the immune system)… Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Urothelial Carcinoma
What is being tested?
ZKAB001 5mg/kg, ZKAB001 10mg/kg and ZKAB001 15mg/kg
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteChina
Study dates
10 Oct 2018to 23 Jun 2023
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 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • The subject voluntarily gives written informed consent to participate in the study.
  • Female and male patients aged between 18 and 75 (inclusive).
  • Subjects must have a histologically and/or cytologically confirmed diagnosis of urothelial carcinoma and the recurrence or metastasis is confirmed again after recurrence, and must have failed or are intolerable to standard therapies or for whom no standard therapies exist.
  • Must have measurable disease with at least 1 unidimensional measurable lesion (recorded as the maximum diameter) based on RECIST 1.1.
  • Eastern Cooperative Oncology Group(ECOG) performance status of 0 or 1, with estimated life expectancy of at least 3 months.
  • Adequate blood routine, hepatic and renal function:
  • 1)neutrophil count (ANC) absolutely acuity≥1.5 x 109 / L; 2)platelet count≥80 x 109 / L ; 3)hemoglobin≥90 g/L; 4)serum albumin≥28 g/L; 5)bilirubin≤1.5 x ULN (upper limit of normal ); 6)ALT and AST≤1.5 x ULN, such as liver metastasis, ALT (alanine transaminase) and AST≤5 x ULN; 7)serum Cr≤1.25 x ULN or endogenous creatinine clearance≥50 ml/min (according Cockcroft Gault formula).
  • 7.Female patients of reproductive age should take effective contraception during the study period and within 3 months after the study treatment period. The serum or urine human chorionic gonadotropin (HCG) examination must be negative within 7 days before the study was enrolled.

Who cannot join

  • Any active autoimmune disease or history of autoimmune disease (such as, but not limited to, interstitial pneumonia, uveitis, enteritis, hepatitis, arthritis, nephritis, pituitary inflammation, hyperthyroidism, hypothyroidism, etc.); Patients with vitiligo or asthma in childhood, and still need medical intervention in adult; Patients need bronchodilators for medical intervention of asthma.
  • Patients are using immunosuppressive agents, or systemic, or absorbable topical corticosteroid medications to achieve immunosuppressive purposes (doses >10mg/day prednisone or equivalent), which is ongoing 2 weeks before enrollment.
  • Have received any form of organ transplantation, including allogeneic stem cell transplantation.
  • Known allergy to macromolecular protein inhibitors or any of the components of ZKAB001.
  • Suffering from other malignant tumors other than this diseases in 5 years except skin basal cell and squamous cell carcinoma or cervical carcinoma in situ.
  • Central nervous system metastases with clinical symptoms (such as cerebral edema and brain metastases requiring corticosteroid intervention). Previous treatment with brain or meningeal metastasis, such as clinical stabilization (MRI) less than 2 months, or systemic corticosteroid (dose >10mg/day prednisone or equivalent) less than 2 weeks.
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  • Patients with clinical symptoms or heart diseases that cannot be well controlled, such as heart failure above New York Heart Association (NYHA) 2 grade, unstable angina pectoris, myocardial infarction in 1 year, and clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention, left ventricular ejection fraction < 50% at rest as shown in the ultrasound cardiogram.
  • Patients who had received radiotherapy, chemotherapy, surgery or molecular targeted therapy before, were given less than 4 weeks or 5 half-life (longer time) after the treatment (if treated with nitrosourea or mitomycin previously, the time interval between the end of chemotherapy and study inclusion was less than 6 weeks); Adverse events caused by previous treatment did not recover to level 1 of CTCAE, except for hair loss.
  • Active infection, or unexplained fever> 38.5 degrees during screening period or before the first dose of ZKAB001 (subjects with fever from the tumor could be enrolled upon investigator's decision).
  • Human immunodeficiency virus (HIV) positive, syphilis spirochete positive, untreated active hepatitis.
  • The patient is participating in other clinical studies or is less than 1 month away from the end of the previous clinical study.
  • Patients may need to receive other systemic cancer treatment during study period.
  • Prior therapy with an anti-PD 1, anti-PD L1, or anti-CTLA-4 (Cytotoxic T Lymphocyte Antigen-4) antibody (or any other agents that target immunoregulatory receptor).
  • Recent history of prophylactic non-cancer vaccination (such as seasonal influenza vaccine and human papillomavirus (HPV) vaccine) within 28 days before screening.
  • History of mental drug abuse, alcohol abuse or drug abuse.
  • Pregnant or lactating women.
  • Any mental condition that prevents the understanding or provision of an informed consent.
  • It is determined by the investigator that the patient has other factors that may lead to the termination of the study, such as other serious diseases or serious laboratory test abnormalities or other factors that may affect the safety of the subjects, family or social factors that may affect the study data and sample collection.

Trial locations and contacts

1 site in 1 country.

Jun Guo, MD contact

010-88121122

guoj307@126.com

China1 site, 1 recruiting

  • Beijing Tumor Hospital

    Beijing, Beijing Municipality, 100000

    Jun Guo, M.D

    Recruiting

Other trials in China

About this study

Official title: An Open-label, Dose-escalation, Bi-weekly Phase I+II Clinical Trial in Treating Patients With Locally Advanced and Metastatic Urothelial Carcinoma

This is a Phase 1+2, open-label, dose-escalation, and multidose study, aiming to investigate the safety, tolerability and pharmacokinetics of ZKAB001 (a fully human monoclonal antibody targeting the Programmed Death - Ligand 1 (PD-L1) membrane receptor on T lymphocytes and other cells of the immune system) administered every 14 days in subjects with locally advanced and metastatic urothelial carcinoma.

Read the detailed description

The study will consist of 4 periods: Screening (up to 28 days), Lead-in period (Day -28), Treatment (up to 24 cycles or 1 year, whichever occurs first）, and Follow-up (up to 1 year). There will be a lead-in period on Day -28 for each dose escalation cohort in which the single-dose pharmacokinetics(PK) of ZKAB001 will be characterized prior to initiation of continuous dosing in the first cycle of treatment. The lead-in period duration, PK time-points, doses and/or regimens used in subsequent cohorts may be modified based on the exposure (AUC) observed during the lead-in period (although the number of PK samples will not be increased). Treatment of continuous dosing is up to 24 cycles or 1 year, until as per investigator's opinion, subjects experience disease progression (evaluated by RECIST 1.1 and immune-related response criteria irRECIST), no clinical benefit, or intolerable toxicity. If investigators suspect subjects experience pseudoprogression or has evidence to prove "mixed response", subjects can continue to accept treatment as investigator decided.

Being tested
ZKAB001 5mg/kg, ZKAB001 10mg/kg, ZKAB001 15mg/kg
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.

  • ZKAB001 5mg/kgDrug

    Also called PD-L1 monoclonal antibody

    5mg/kg/times bi-week IV administration of ZKAB001

  • ZKAB001 10mg/kgDrug

    Also called PD-L1 monoclonal antibody

    10mg/kg/times bi-week IV administration of ZKAB001

  • ZKAB001 15mg/kgDrug

    Also called PD-L1 monoclonal antibody

    15mg/kg/times bi-week IV administration of ZKAB001

Study groups in NCT03676946
Study groupRoleWhat they receive
ZKAB001 5mg/kgExperimentalThree or six patients will be treated with the dose of 5 mg/kg/time of ZKAB001 IV bi-weekly. DLT will be observed within 28 days after administration.
Receives: Drug: ZKAB001 5mg/kg
ZKAB001 10mg/kgExperimentalThree or six patients will be treated with the dose of 5 mg/kg/time of ZKAB001 IV bi-weekly. DLT will be observed within 28 days after administration.
Receives: Drug: ZKAB001 10mg/kg
ZKAB001 15mg/kgExperimentalThree or six patients will be treated with the dose of 5 mg/kg/time of ZKAB001 IV bi-weekly. DLT will be observed within 28 days after administration.
Receives: Drug: ZKAB001 15mg/kg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose limiting toxicity (DLT)

    Adverse events of level 3 or above related to the study drug occurring within 28 days after the first dose as assessed by CTCAE v4.0.

    Measured: 28 days after first dose

Secondary outcomes (12)

  1. Maximal tolerable dose(MTD)

    DLT occurs in less than 1/6 subjects, this lower dose is defined as MTD.

    Measured: 28 days after first dose

  2. The overall response rate(ORR)

    The proportion of subjects who achieve the optimal objective response rate (PR or CR).

    Measured: through study completion, an average of 2 year

  3. AUC(0-t)

    Area under curve 0-t

    Measured: 24 periods or 1 year

  4. AUC(INF)

    Area under curve INF

    Measured: 24 periods or 1 year

  5. Cmax

    Peak concentration

    Measured: 24 periods or 1 year

  6. Tmax

    Peak time

    Measured: 24 periods or 1 year

  7. T1/2

    Half life

    Measured: 24 periods or 1 year

  8. Vss

    Steady-state apparent volume of distribution based on plasma concentration

    Measured: 24 periods or 1 year

  9. Total body clearance(CLT)

    Total body clearance

    Measured: 24 periods or 1 year

  10. Cmin

    The trough value at steady state

    Measured: 24 periods or 1 year

  11. The percentage of the receptors of PD-L1 in CD14+(cluster of differentiation 14+) monocytes and CD3+(cluster of differentiation 3+) T cells

    To detected the percentage of the receptors of PD-L1 in CD14+ monocytes and CD3+ T cells.

    Measured: through study completion, an average of 2 year

  12. The number of subjects presenting detectable anti drug antibodies (ADAs)

    To evaluated the number of subjects presenting detectable anti drug antibodies (ADAs).

    Measured: through study completion, an average of 2 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Sep 2018
  2. Study start10 Oct 2018 (estimated)
  3. Primary completion14 Feb 2020 (estimated)
  4. Study completion23 Jun 2023 (estimated)

Resources

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
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
15 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03676946
Sponsor's protocol ID
NTL-LEES-2017-01
Status last verified
Sep 2018
First submitted
13 Sep 2018
Last updated
26 Sep 2018
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing ZKAB001 5mg/kg, ZKAB001 10mg/kg and ZKAB001 15mg/kg in people with Urothelial Carcinoma, run by Lee's Pharmaceutical Limited 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 8 inclusion and 18 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 26 Sep 2018. 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 Jun Guo, MD (010-88121122, guoj307@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose limiting toxicity (DLT) (time frame: 28 days after first dose). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03676946.

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 26 Sep 2018.

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