Bladder CancerPhase 1/2NCT06364956
Clinical Trail of Neoadjuvant of Tislelizumab Combined With Palbociclib in Patients With Platinum-refractory Bladder Urothelial Carcinoma
A Phase 1/2 study testing Tislelizumab combined with two predefined dose groups of palbociclib and RP2D dose Of Tislelizumab combined with palbociclib was selected for phase II clinical trial. in people with Bladder Cancer, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University at 8 sites in China.
Trial summary
In order to explore the safety and antitumor efficacy of different doses of CDK4/6 inhibitor Palbociclib in combination with the Tislelizumab in platinum-refractory cT2-4aN0M0 bladder urothelial carcinoma, a phase Ib/II study was conducted. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bladder Cancer
- What is being tested?
- Tislelizumab combined with two predefined dose groups of palbociclib and RP2D dose Of Tislelizumab combined with palbociclib was selected for phase II clinical trial.
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 8 sitesChina
- Study dates
- 15 May 2024to Jun 2026
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Voluntarily participate in this study, able to provide written informed consent and can understand and agree to comply with the requirements of the study and schedule of assessments.
- Aged over 18 years on day of signing informed consent
- Patients with urothelial bladder cancer, having residual lesions following TURBT surgery, staged cT2-T4aN0M0 as histologically confirmed and radiologically assessed based on the TNM Staging System for Bladder Cancer of American Joint Committee on Cancers (AJCC) ; predominantly histological classification of urothelial carcinoma (at least 50%) for patients with mixed-histology bladder cancer.
- Patients with mutations or copy number variation (CNV) alterations, such as CDKN2A, CDKN2B CNV deletion, indicating the activation of cell cycle-related pathways.
- ECOG Performance Status 0 or 1
- Ineligible for Cisplatin treatment as judged by investigator. Patients who are ineligible for Cisplatin chemotherapy should meet at least one of the following criteria: ECOG performance status > 1 or Karnofsky performance status 60% to 70%; creatinine clearance less than 60 mL/min; ≥ Grade 2 hearing loss according to NCI-CTCAE v5.0; ≥ Grade 2 neuropathy peripheral according to NCI-CTCAE v5.0; ≥ Grade 3 cardiac failure according to New York Heart Association Cardiac Function Classification
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- Patients will receive radical cystectomy following neoadjuvant therapy as assessed by investigator, meet surgical indication and are willing to receive the surgery.
- Tumor tissue samples collected during TURBT must be available, and relevant pathological reports are required. Fresh surgical tissue samples or pathological slides are optional
- Have adequate organ function as indicated by the following screening laboratory values (obtained ≤ 14 days prior to enrollment):
- a.Patients must not be administered with growth factors ≤ 14 days prior to sampling for the screening tests of: i.Absolute neutrophil count ≥ 1.5 x 109/L ii.Platelets ≥ 90 x 109/L iii.Hemoglobin ≥ 90 g/L b.International normalized ratio or activated partial thromboplastin time ≤ 1.5 x upper limit of normal (ULN).
- c.Serum total bilirubin ≤ 1.5 x ULN (≤ 3 x ULN, if Gilbert's syndrome or if indirect bilirubin concentrations were suggestive of extrahepatic source of the elevation).
- e.Aspartate transaminase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ≤ 2.5 x ULN f.Patients can tolerate major abdominal surgery as suggested by pulmonary function test results
- Unpregnant females or females of childbearing potential must be willing to use a highly effective contraceptive method for the duration of the study, and ≥ 120 days after the last dose of Tislelizumab or chemotherapy agents, whichever is later, and have a negative urine or serum pregnancy test ≤ 7 days prior to enrollment.
Who cannot join
- Received prior therapies targeting PD-1, PD-L1, PD-L2, CTLA4, or other antibodies or drugs specifically targeting T-cell costimulation or checkpoint pathways.
- Received other approved systemic anticancer therapies or systemic immunomodulators (including but not limited to interferon, interleukin 2, and tumor necrosis factor) within 28 days prior to enrollment.
- Received prior radiotherapy for bladder cancer.
- Received anticancer drug therapies with the following exceptions:
- For patients who have received prior systemic chemotherapy, a treatment-free interval of at least 12 months from the last dose of chemotherapy until the start of neoadjuvant therapy is required
- Local intravesical chemotherapy or immunotherapy must be discontinued at least 1 week before start of the investigational neoadjuvant medication treatment
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- Received major surgery or had major trauma within 28 days prior to enrollment (vascular access placement and TURBT are not considered as major surgeries).
- Severe chronic or active infections requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days prior to enrollment (HBV infection will be ruled out according to Exclusion Criteria # 12).
- Received live vaccines within 28 days prior to enrollment (seasonal vaccines for influenza are generally inactivated vaccines and are allowed. Intranasal vaccines are live vaccines and are not allowed.)
- Active autoimmune diseases that requires systemic treatment and may impact study treatment as assessed by investigator
- Any condition that requires extensive chronic treatment with either hormones or any other immunosuppressive medications that may impact study treatment as assessed by investigator.
- With history of potassium, sodium, calcium abnormalities or hypoalbuminemia, interstitial lung disease, pneumonitis or history of uncontrolled systemic diseases, including diabetes, hypertension, cardiovascular diseases (such as active cardiac diseases within 6 months prior to enrollment, including: severe/unstable angina pectoris, myocardial infarction, symptomatic congestive heart failure, and ventricular arrhythmia requiring medical treatment) that may impact study treatment as assessed by investigator.
- HBV Patients with untreated chronic hepatitis B or hepatitis B virus (HBV) carriers with HBV DNA ≥ 500 IU/mL (2500 copies/mL) cannot be enrolled. Note: inactive hepatitis B surface antigen (HBsAg) carriers and patients who received continuous antiviral treatments and have stable active hepatitis B infection (HBV DNA < 500 IU/mL or < 2500 copies/mL) can be enrolled. HBV DNA testing will be performed only for patients testing positive for antibody to hepatitis B core antigen (anti-HBc).
- Patients with active hepatitis C cannot be enrolled. Patients with a negative HCV antibody test at Screening or positive HCV antibody test followed by a negative HCV RNA test at Screening can be enrolled. The HCV RNA test will be performed only for patients testing positive for HCV antibody.
- History of immunodeficiency (including human immunodeficiency virus [HIV] positive, other acquired, congenital immunodeficiency diseases) or history of allogeneic stem cell transplantation or organ transplantation.
- Known hypersensitivity to other monoclonal antibodies.
- Known hypersensitivity to any investigational agents or their excipients.
- Patients with toxicities or AEs (as a result of any prior treatment) which have not recovered to baseline or stabilized, except for toxicities or AEs not considered a likely safety risk (eg, alopecia, neuropathy, and specific laboratory abnormalities) as assessed by investigator.
- Underlying medical conditions or alcohol or drug abuse or dependence that were to be unfavorable for the administration of investigational agents or may have affected the interpretation of the results or rendered the patient at high risk from treatment complications.
- Concurrent participation in another therapeutic clinical study.
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
8 sites in 1 country
China8 sites, 8 recruiting
- Recruiting
Hunan Cancer Hospital
Changsha, Hunan
Yu Xie, Ph.D
- Recruiting
Xiangya Hospital, Central South University
Changsha, Hunan
Xiongbing Zu, Ph.D
- Recruiting
Nanfang Hospital, Southern Medical University
Guangzhou, Guangdong
Fan Wu, Ph.D
- Recruiting
Sun Yat-sen Memorial Hospital
Guangzhou, Guangdong
Wenlong Zhong, Ph.D
- Recruiting
The First Affiliated Hospital of Sun Yat-sen University
Guangzhou, Guangdong
Junxin Chen, Ph.D
- Recruiting
The Third Affiliated Hospital of Sun Yat-sen University
Guangzhou, Guangdong
Yun Luo, Ph.D
- Recruiting
Zhujiang Hospital of Southern Medical University
Guangzhou, Guangdong
Ebai Xu, Ph.D
- Recruiting
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei
Zheng Liu, Ph.D
About this study
Official title: A Phase Ib/II Prospective Study to Evaluate the Safety and Efficacy of the Combination of Neoadjuvant Palbociclib and Tislelizumab in Platinum-refractory cT2-4aN0M0 Bladder Urothelial Carcinoma.
In order to explore the safety and antitumor efficacy of different doses of CDK4/6 inhibitor Palbociclib in combination with the Tislelizumab in platinum-refractory cT2-4aN0M0 bladder urothelial carcinoma, a phase Ib/II study was conducted.
This study will adopt a 3+3 design and include two predefined dose groups of palbociclib: 100mg QD, 125mg QD. Initially, Tislelizumab, 200 mg administered by intravenous infusion on Day 1 of each 21-day will be administered in combination. The trial will use the first cycle (28 days) as the observation period for tolerability, observing and evaluating the occurrence of DLTs after medication and determining the maximum tolerated dose/maximum administered dose (MTD/MAD) and recommended phase 2 dose (RP2D) of the combination therapy (30 patients) .
This study provide further evidence for improving the efficacy of neoadjuvant treatment forplatinum-refractory cT2-4aN0M0 bladder urothelial carcinoma and to offer new options for precision treatment of bladder cancer.
- Conditions
- Bladder Cancer
- Being tested
- Tislelizumab combined with two predefined dose groups of palbociclib, RP2D dose Of Tislelizumab combined with palbociclib was selected for phase II clinical trial.
- Keywords
- Tislelizumab, Palbociclib, neoadjuvant, bladder cancer
- Medical subject headings
- Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tislelizumab combined with two predefined dose groups of palbociclibDrug
Tislelizumab, 200mg q3W, combined with two predefined dose groups of palbociclib: 100mg QD and 125mg QD, separately.
RP2D dose Of Tislelizumab combined with palbociclib was selected for phase II clinical trial.Drug
After the exploration of Tislelizumab, 200mg q3W combined with palbociclib, and the maximal tolerated dose (MTD) was determined, then RP2D dose of Tislelizumab combined with palbociclib was selected for phase II clinical trial.
| Study group | Role | What they receive |
|---|---|---|
| Phase Ib clinical trial | Experimental | Tislelizumab, 200mg q3W, combined with two predefined dose groups of palbociclib: 100mg QD and 125mg QD, separately. Receives: Drug: Tislelizumab combined with two predefined dose groups of palbociclib |
| Phase II clinical trial | Experimental | Tislelizumab, 200mg q3W, combined with RP2D dose of palbociclib was selected for phase II clinical trial. Receives: Drug: RP2D dose Of Tislelizumab combined with palbociclib was selected for phase II clinical trial. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: The safety dose of the combination of Tislelizumab and Palbociclib
The study aims to evaluate the safety dose of the combination of Tislelizumab combined with palbociclib in patients with cT2-4aN0M0 bladder cancer. The safety dose was according to "3+3" dose escalation principle.
Participants with dose-limiting toxicity (DLT) as assessed by NCI CTC 5.0 and the administered drug dose.
Measured: 12 months
Phase II: Percentage of Participants With Pathological Complete Response(pCR)
Pathological evaluation of the resected tumor tissue and regional lymph nodes showed no residual tumor cells, complete disappearance of the tumor lesions, and no evidence of new lesions.
Measured: 24 months
Secondary outcomes (4)
Percentage of Participants With Pathological Downstaging(pDS)
The pathological downstaging rate is defined as the evaluation of whether the staging is degraded to ≤ T2 based on the post-surgery pathological findings. The rates of cT2N0 → pT0N0, cT3-4aN0 → pT0N0, cT2N0 → ≤ pT1N0, cT3-4aN0 → ≤ pT1N0 will be calculated, and the 2 sided Clopper-Pearson 95% confidence interval (CI) of pathological downstaging rate will be calculated to assess the precision of the estimated pathological downstaging rate.
Measured: 24 months
Event-free survival (EFS)
Event-free survival (EFS) was determined from start date of the first dose of neoadjuvant treatment to date of disease progression, death from any cause, or onset of other tumors.
Measured: 24 months
overall survival (OS)
OS was measured from the date the participant started study to death for any reason.
Measured: 24 months
Safety and AE
Number of unique patients who had a treatment-related (possible, probable, or definite) adverse event using the Medical Dictionary for Regulatory Activities (MedDRA) terms and graded per NCI-CTCAE v5.0.
Number and Grade of patients who had a surgery-related adverse event (surgery-related AE) will be measured according to the Clavien-Dindo classification.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2024
- Study start15 May 2024
- Primary completionJun 2026 (estimated)
- Study completionJun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bladder CancerStudies of the same condition, open and under way.
- More trials run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityThe sponsor's other registered studies.
- 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tianxin Lin, Ph.D, Study chair, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06364956
- Sponsor's protocol ID
- SYSKY-2024-124-02
- Status last verified
- Aug 2025
- First submitted
- 6 Mar 2024
- Last updated
- 11 Aug 2025
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II Prospective Study to Evaluate the Safety and Efficacy of the Combination of Neoadjuvant Palbociclib and Tislelizumab in Platinum-refractory cT2-4aN0M0 Bladder Urothelial Carcinoma.
- ClinicalTrials.gov ID
- NCT06364956
- Acronym / sponsor ID
- SYSKY-2024-124-02
- Conditions
- Bladder Cancer
- Keywords
- Tislelizumab, Palbociclib, neoadjuvant, bladder cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityUniversity, hospital or other
- Study start
- 15 May 2024 (actual)
- Primary completion
- Jun 2026 (estimated)
- Study completion
- Jun 2026 (estimated)
- First posted
- 15 Apr 2024 (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.
In order to explore the safety and antitumor efficacy of different doses of CDK4/6 inhibitor Palbociclib in combination with the Tislelizumab in platinum-refractory cT2-4aN0M0 bladder urothelial carcinoma, a phase Ib/II study was conducted.
This study will adopt a 3+3 design and include two predefined dose groups of palbociclib: 100mg QD, 125mg QD. Initially, Tislelizumab, 200 mg administered by intravenous infusion on Day 1 of each 21-day will be administered in combination. The trial will use the first cycle (28 days) as the observation period for tolerability, observing and evaluating the occurrence of DLTs after medication and determining the maximum tolerated dose/maximum administered dose (MTD/MAD) and recommended phase 2 dose (RP2D) of the combination therapy (30 patients) .
This study provide further evidence for improving the efficacy of neoadjuvant treatment forplatinum-refractory cT2-4aN0M0 bladder urothelial carcinoma and to offer new options for precision treatment of bladder cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase Ib clinical trial | Experimental | Drug: Tislelizumab combined with two predefined dose groups of palbociclibTislelizumab, 200mg q3W, combined with two predefined dose groups of palbociclib: 100mg QD and 125mg QD, separately. |
| Phase II clinical trial | Experimental | Drug: RP2D dose Of Tislelizumab combined with palbociclib was selected for phase II clinical trial.Tislelizumab, 200mg q3W, combined with RP2D dose of palbociclib was selected for phase II clinical trial. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Voluntarily participate in this study, able to provide written informed consent and can understand and agree to comply with the requirements of the study and schedule of assessments.
- Aged over 18 years on day of signing informed consent
- Patients with urothelial bladder cancer, having residual lesions following TURBT surgery, staged cT2-T4aN0M0 as histologically confirmed and radiologically assessed based on the TNM Staging System for Bladder Cancer of American Joint Committee on Cancers (AJCC) ; predominantly histological classification of urothelial carcinoma (at least 50%) for patients with mixed-histology bladder cancer.
- Patients with mutations or copy number variation (CNV) alterations, such as CDKN2A, CDKN2B CNV deletion, indicating the activation of cell cycle-related pathways.
- ECOG Performance Status 0 or 1
Key exclusion criteria (20 listed)
- Received prior therapies targeting PD-1, PD-L1, PD-L2, CTLA4, or other antibodies or drugs specifically targeting T-cell costimulation or checkpoint pathways.
- Received other approved systemic anticancer therapies or systemic immunomodulators (including but not limited to interferon, interleukin 2, and tumor necrosis factor) within 28 days prior to enrollment.
- Received prior radiotherapy for bladder cancer.
- Received anticancer drug therapies with the following exceptions:
- Received major surgery or had major trauma within 28 days prior to enrollment (vascular access placement and TURBT are not considered as major surgeries).
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 |
|---|---|---|
| Tislelizumab combined with two predefined dose groups of palbociclibTislelizumab, 200mg q3W, combined with two predefined dose groups of palbociclib: 100mg QD and 125mg QD, separately. | Drug | Phase Ib clinical trial |
| RP2D dose Of Tislelizumab combined with palbociclib was selected for phase II clinical trial.After the exploration of Tislelizumab, 200mg q3W combined with palbociclib, and the maximal tolerated dose (MTD) was determined, then RP2D dose of Tislelizumab combined with palbociclib was selected for phase II clinical trial. | Drug | Phase II clinical trial |
Primary outcome
Phase I: The safety dose of the combination of Tislelizumab and Palbociclib
Time frame: 12 months
The study aims to evaluate the safety dose of the combination of Tislelizumab combined with palbociclib in patients with cT2-4aN0M0 bladder cancer. The safety dose was according to "3+3" dose escalation principle. Participants with dose-limiting toxicity (DLT) as assessed by NCI CTC 5.0 and the administered drug dose.
Phase II: Percentage of Participants With Pathological Complete Response(pCR)
Time frame: 24 months
Pathological evaluation of the resected tumor tissue and regional lymph nodes showed no residual tumor cells, complete disappearance of the tumor lesions, and no evidence of new lesions.
4 secondary outcomes
Percentage of Participants With Pathological Downstaging(pDS)
Time frame: 24 months
Event-free survival (EFS)
Time frame: 24 months
overall survival (OS)
Time frame: 24 months
Safety and AE
Time frame: 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2025.
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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.
Tianxin Lin, Ph.D study chair
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
8 sites 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 Tislelizumab combined with two predefined dose groups of palbociclib and RP2D dose Of Tislelizumab combined with palbociclib was selected for phase II clinical trial. in people with Bladder Cancer, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University at 8 sites 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 13 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: looking for participants now, as of the sponsor's last update on 11 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Wenlong Zhong, Ph.D (020-81338949, zhongwlong3@mail.sysu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase I: The safety dose of the combination of Tislelizumab and Palbociclib (time frame: 12 months). The study lists 2 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 11 Aug 2025.