Cervical CancerPhase 1NCT03676959
A Clinical Study of PD-L1 Antibody ZKAB001（Drug Code） in Recurrent or Metastatic Cervical Cancer
A Phase 1 study testing ZKAB001 5mg/kg, ZKAB001 10mg/kg and ZKAB001 15mg/kg in people with Cervical Cancer, run by Lee's Pharmaceutical Limited at 1 site in China.
Trial summary
This is a Phase 1, open-label, dose-escalation, and multidose study, aiming to investigate the safety, tolerability and pharmacokinetics(PK) 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 years and older, women only
- Conditions the study is for
- Cervical Cancer
- 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
- 101 participants
- Where
- 1 siteChina
- Study dates
- 16 Aug 2018to 15 Oct 2022
- Phase
- Phase 1
- 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 years and older
- Women only
- 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 subjects aged≥18 years.
- Recurrent or metastatic cervical cancer was diagnosed by histopathology or cytology and received first-line platinum-containing regimens that failed or could not be tolerated. The definition of first-line failure: progress during adjuvant therapy or within 6 months after the end of treatment, and the first progress after palliative treatment.
- Based on RECIST1.1, imaging evaluation confirmed that there was at least one measurable disease.
- 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) Absolute neutrophil count（ANC）≥109/L 2) Platelets ≥100x109/L 3) Hemoglobin ≥9g/dL 4) Serum albumin ≥2.8g/dL 5) Bilirubin ≤1.5x Upper limit of normal（ULN） 6) ALT and AST ≤1.5xULN, if If liver metastases are present, alanine transaminase（ALT） and aspartate transaminase（AST） should be ≤5xULN 7) Creatinine clearance rate ≥50ml/min (Cockcroft-Gault equation) 7.Female reproductive subjects 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 subject is enrolled.
Who cannot join
- There are known active or suspected autoimmune diseases. Those who are in a stable state and do not need systemic immunosuppressive therapy can be included.
- 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 for skin basal cell and squamous cell carcinoma.
- 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 diseases of the heart 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, have left ventricular ejection fraction < 50% at rest in the ultrasound cardiogram.
- Patients who had received radiotherapy, chemotherapy, surgery or molecular targeted therapy before, were given less than 4 weeks.
- Within 14 days before the first use of the drug, any active infection requiring systematic anti-infective treatment.
- Human immunodeficiency virus (HIV) positive, untreated active hepatitis (hepatitis B surface antigen positive and peripheral blood HBV-DNA titer ≥ 500IU/ml or positive copy number detected by the research center; hepatitis C virus antibody positive)
- There is a history of active pulmonary tuberculosis within 1 year before entering the group.
- 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.
- Received blood transfusion and hematopoietic stimulating factors, such as colony stimulating factor, erythropoietin, thrombopoietin, etc., within 14 days before screening.
- 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).
- Subjects who received live vaccine within 4 weeks 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 patients, family or social factors that may affect the study data and sample collection.
Trial locations and contacts
1 site in 1 country.
hong Fang, master contact
China1 site, 1 recruiting
- Recruiting
Chinese Academy of Medical Sciences and Peking Union Medical College
Beijing, Beijing Municipality, 100000
About this study
Official title: An Open-label, Dose-escalation, Bi-weekly Phase I Clinical Trial in Treating Patients With Recurrent or Metastatic Cervical Cancer
This is a Phase 1, open-label, dose-escalation, and multidose study, aiming to investigate the safety, tolerability and pharmacokinetics(PK) 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 recurrent or metastatic cervical cancer.
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 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.
The study was divided into two stages. After the recommended phase II dose (RP2D) is determined in the first stage, the sample size will be amplified with RP2D in the second stage. When a total of 15 cases are included in the two stages, an interim analysis will be conducted to decide whether to expand the total number of cases to 60 based on the results of the analysis. If more than 2 cases of response will be observed in 15 cervical cancer subjects, 45 cases (with a total sample size of 60 cases) could be included to further observe the safety and efficacy.
- Conditions
- Cervical Cancer
- Being tested
- ZKAB001 5mg/kg, ZKAB001 10mg/kg, ZKAB001 15mg/kg
- Medical subject headings
- Uterine Cervical Neoplasms
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 group | Role | What they receive |
|---|---|---|
| ZKAB001 5mg/kg | Experimental | Three 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 10 mg/kg | Experimental | Three or six patients will be treated with the dose of 10 mg/kg/time of ZKAB001 IV bi-weekly. DLT will be observed within 28 days after administration. Receives: Drug: ZKAB001 10mg/kg |
| ZKAB001 15 mg/kg | Experimental | Three or six patients will be treated with the dose of 15 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.
RP2D
Recommended phase II dose.
Measured: 28 days after first dose
Objective response rate
The proportion of subjects who achieved the best objective response rate (PR or CR).
Measured: 2 years
Tolerance
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Measured: 2 years
Secondary outcomes (8)
Effect of ZKAB001 on T cell function and cytokine expression
The response of CD4+ and CD8+ cells to tumor at baseline and after each administration will be detected by flow cytometry.
Measured: through study completion, an average of 2 years
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 years
Receptor occupancy
Monocytes will be isolated from peripheral blood before each cycle of administration, and the receptor occupancy of PD-L1 on CD3+T cells will be determined.
Measured: through study completion, an average of 2 years
PD-L1 expression
Detection of PD-L1 expression in tumor tissues.
Measured: through study completion, an average of 2 years
progression free survival（PFS）
Evaluate the PFS of the study population
Measured: through study completion, an average of 2 years
overall survival
Evaluate the OS of the study population
Measured: through study completion, an average of 2 years
duration of response
Evaluate the DOR of the study population
Measured: through study completion, an average of 2 years
best of response
Evaluate the BOR of the study population
Measured: through study completion, an average of 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2018
- Study start16 Aug 2018
- Primary completion15 May 2022 (estimated)
- Study completion15 Oct 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cervical CancerStudies 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 101 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Lee's Pharmaceutical Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- lingying Wu, M.D, Study director, Tumor Hospital of the Chinese Academy of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03676959
- Sponsor's protocol ID
- NTL-LEES-2017-02
- Status last verified
- May 2021
- First submitted
- 12 Sep 2018
- Last updated
- 13 May 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
An J, Tang J, Li BX, Xiong H, Qiu H, Luo L, Wang L, Wang D, Zhou Q, Xu Q, Song H, Zhang Y, Zhang H, Li Y, Yu X, Zhang J, Ng R, Zhao W, Wong M, Dai X, Li G, Wu L. Efficacy and Safety of the Anti-PD-L1 mAb Socazolimab for Recurrent or Metastatic Cervical Cancer: a Phase I Dose-Escalation and Expansion Study. Clin Cancer Res. 2022 Dec 1;28(23):5098-5106. doi: 10.1158/1078-0432.CCR-22-1280.
PubMed 36136294
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Dose-escalation, Bi-weekly Phase I Clinical Trial in Treating Patients With Recurrent or Metastatic Cervical Cancer
- ClinicalTrials.gov ID
- NCT03676959
- Acronym / sponsor ID
- NTL-LEES-2017-02
- Conditions
- Cervical Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 101 participants (estimated)
- Lead sponsor
- Lee's Pharmaceutical LimitedIndustry (pharma, biotech, devices)
- Study start
- 16 Aug 2018 (actual)
- Primary completion
- 15 May 2022 (estimated)
- Study completion
- 15 Oct 2022 (estimated)
- First posted
- 19 Sep 2018 (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.
This is a Phase 1, open-label, dose-escalation, and multidose study, aiming to investigate the safety, tolerability and pharmacokinetics(PK) 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 recurrent or metastatic cervical cancer.
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 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.
The study was divided into two stages. After the recommended phase II dose (RP2D) is determined in the first stage, the sample size will be amplified with RP2D in the second stage. When a total of 15 cases are included in the two stages, an interim analysis will be conducted to decide whether to expand the total number of cases to 60 based on the results of the analysis. If more than 2 cases of response will be observed in 15 cervical cancer subjects, 45 cases (with a total sample size of 60 cases) could be included to further observe the safety and efficacy.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| ZKAB001 5mg/kg | Experimental | Drug: ZKAB001 5mg/kgThree 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. |
| ZKAB001 10 mg/kg | Experimental | Drug: ZKAB001 10mg/kgThree or six patients will be treated with the dose of 10 mg/kg/time of ZKAB001 IV bi-weekly. DLT will be observed within 28 days after administration. |
| ZKAB001 15 mg/kg | Experimental | Drug: ZKAB001 15mg/kgThree or six patients will be treated with the dose of 15 mg/kg/time of ZKAB001 IV bi-weekly. DLT will be observed within 28 days after administration. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- The subject voluntarily gives written informed consent to participate in the study.
- Female subjects aged≥18 years.
- Recurrent or metastatic cervical cancer was diagnosed by histopathology or cytology and received first-line platinum-containing regimens that failed or could not be tolerated. The definition of first-line failure: progress during adjuvant therapy or within 6 months after the end of treatment, and the first progress after palliative treatment.
- Based on RECIST1.1, imaging evaluation confirmed that there was at least one measurable disease.
- Eastern Cooperative Oncology Group（ECOG） performance status of 0 or 1, with estimated life expectancy of at least 3 months.
Key exclusion criteria (20 listed)
- There are known active or suspected autoimmune diseases. Those who are in a stable state and do not need systemic immunosuppressive therapy can be included.
- 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 for skin basal cell and squamous cell carcinoma.
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 |
|---|---|---|
| ZKAB001 5mg/kgAlso: PD-L1 monoclonal antibody5mg/kg/times bi-week IV administration of ZKAB001 | Drug | ZKAB001 5mg/kg |
| ZKAB001 10mg/kgAlso: PD-L1 monoclonal antibody10mg/kg/times bi-week IV administration of ZKAB001 | Drug | ZKAB001 10 mg/kg |
| ZKAB001 15mg/kgAlso: PD-L1 monoclonal antibody15mg/kg/times bi-week IV administration of ZKAB001 | Drug | ZKAB001 15 mg/kg |
Primary outcome
RP2D
Time frame: 28 days after first dose
Recommended phase II dose.
Objective response rate
Time frame: 2 years
The proportion of subjects who achieved the best objective response rate (PR or CR).
Tolerance
Time frame: 2 years
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
8 secondary outcomes
Effect of ZKAB001 on T cell function and cytokine expression
Time frame: through study completion, an average of 2 years
The number of subjects presenting detectable anti drug antibodies (ADAs)
Time frame: through study completion, an average of 2 years
Receptor occupancy
Time frame: through study completion, an average of 2 years
PD-L1 expression
Time frame: through study completion, an average of 2 years
progression free survival（PFS）
Time frame: through study completion, an average of 2 years
overall survival
Time frame: through study completion, an average of 2 years
duration of response
Time frame: through study completion, an average of 2 years
best of response
Time frame: through study completion, an average of 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2021.
- Derived from this study: PubMed 36136294An J, Tang J, Li BX, Xiong H, Qiu H, Luo L, Wang L, Wang D, Zhou Q, Xu Q, Song H, Zhang Y, Zhang H, Li Y, Yu X, Zhang J, Ng R, Zhao W, Wong M, Dai X, Li G, Wu L. Efficacy and Safety of the Anti-PD-L1 mAb Socazolimab for Recurrent or Metastatic Cervical Cancer: a Phase I Dose-Escalation and Expansion Study. Clin Cancer Res. 2022 Dec 1;28(23):5098-5106. doi: 10.1158/1078-0432.CCR-22-1280.
- Individual participant dataSharing planned: No
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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.
hong Fang, master contact
lingying Wu, M.D study director
Tumor Hospital of the Chinese Academy of Medical Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ZKAB001 5mg/kg, ZKAB001 10mg/kg and ZKAB001 15mg/kg in people with Cervical Cancer, 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 7 inclusion and 20 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 13 May 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 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.
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 lingying Wu, M.D (13910865483, wulingying@csco.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
RP2D (time frame: 28 days after first dose). 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?
On the ClinicalTrials.gov record for NCT03676959, which also lists 1 linked publication.
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 13 May 2021.