Muscle Invasive Bladder CancerPhase 1/2ANTICIPATENCT04813107
A Study to Evaluate the Safety and Efficacy of Oral APL-1202 in Combination With Tislelizumab Compared to Tislelizumab Alone as Neoadjuvant Therapy in Patients With Muscle Invasive Bladder Cancer
A Phase 1/2 study testing APL-1202 in combination with tislelizumab and Tislelizumab alone in people with Muscle Invasive Bladder Cancer, run by Jiangsu Yahong Meditech Co., Ltd aka Asieris at 2 sites in 2 countries.
Trial summary
This trial is designed to evaluate the safety, efficacy, and biomarker response of APL-1202 in combination with tislelizumab as neoadjuvant therapy for patients with MIBC who are cisplatin ineligible or refuse cisplatin-based chemotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Muscle Invasive Bladder Cancer
- What is being tested?
- APL-1202 in combination with tislelizumab and Tislelizumab alone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 79 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 28 Dec 2021to 1 Mar 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willing and able to provide written informed consent.
- Age ≥ 18 years.
- Histopathologically confirmed transitional cell carcinoma of the bladder. Patients with mixed histologies are required to have a dominant (i.e. > 50%) transitional cell pattern.
- Radical cystectomy is planned (according to local guidelines).
- Patients who refuse neoadjuvant cisplatin based chemotherapy or in whom neoadjuvant cisplatin based therapy is contraindicated. Contraindications to cisplatin is defined by meeting at least one of the following criteria:
- Impaired renal function with calculated CrCl 30 to 59 mL/min (by Cockcroft-Gault equation).
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- Eastern Cooperative Oncology Group (ECOG) Performance Status 2.
- CTCAE v.5 Grade ≥2 audiometric hearing loss.
- In the clinical judgement of the investigator, potential adverse effects from cisplatin-based neoadjuvant chemotherapy outweighs its benefits.
- Clinical stage T2-T4a N0 M0 disease by CT (or MRI) (within 4 weeks of randomization).
- Residual disease after transurethral resection of bladder (TURB) (surgical opinion, cystoscopy or radiological presence).
- Availability of representative formalin-fixed paraffin-embedded (FFPE) tumor specimens or unstained slides, with an associated pathology report, and determined to be evaluable for tumor PD-L1 expression prior to study enrollment;
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
- Adequate hematologic and end-organ functions:
- Hemoglobin > 9.0 g/dL;
- Absolute neutrophil count (ANC) > 1.5×109 /L;
- Platelet count > 100×109 /L;
- Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN).
- Aspartate aminotransferase (AST) /alanine aminotransferase (ALT) ≤ 2.5 x institutional upper limit of normal ULN.
- CrCl (calculated using Cockcroft-Gault equation) ≥ 30 mL/min (calculated CrCl ≥ 50 mL/min in Phase Ⅰ: Dose-Escalation).
- INR < 1.5. This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose.
- Female patients should be surgically sterilized or post-menopausal or must agree to take effective contraceptive measures during the treatment. Male patients must be surgically sterilized or must agree to take effective contraceptive measures during treatment. Patients must continue to take contraceptive measures for 3 months after the investigational therapy was completed.
Who cannot join
- Previous systemic therapy for bladder cancer.
- Malignancies other than urothelial bladder cancer within 5 years prior to cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ of breast treated surgically with curative intent).
- Evidence of measurable nodal or metastatic disease.
- Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome).
- Pregnant female patients. All female patients with a positive pregnancy test within 2 weeks prior to the first dose of study treatment will be excluded from the study.
- Significant cardiovascular disease, such as New York Heart Association cardiac disease (more than Class II), myocardial infarction within 3 months prior to enrollment, unstable arrhythmias, or unstable angina.
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- Severe infections within 4 weeks prior to enrollment in the study including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
- Major surgical procedure within 4 weeks prior to enrollment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis.
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
- Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the tislelizumab or APL-1202 formulation.
- History of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
- History of autoimmune-related hypothyroidism, unless on a stable dose of thyroid-replacement hormone.
- History of idiopathic pulmonary fibrosis.
- Uncontrolled Type 1 diabetes mellitus.
- Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or calcium > 12 mg/dL or corrected serum calcium > ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab.
- Prior allogeneic stem cell or solid organ transplantation.
- Positive test for HIV.
- Uncontrolled hepatitis infection.
- Active tuberculosis.
- Optic nerve disorders or with a history of optic nerve disorders.
- Cataract or with a history of cataract.
- Prior treatment with anti-programmed death-1 (PD-1), or anti-PD-L1 therapeutic antibody or pathway-targeting agents.
- Patients taking regular oral steroids, above the allowed limit of 10 mg/day methylprednisolone/prednisone or analogues, for any reason. Patients must not have had steroids for 4 weeks prior to study entry.
- Administration of vaccine within 4 weeks prior to enrollment or anticipation that such a vaccine will be required during the study.
- Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 4 weeks prior to enrollment.
- Treatment with systemic immunostimulatory agents within 4 weeks prior to enrollment.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site, 1 recruiting
- Recruiting
Mount Sinai Medical Center
New York, New York, 10001
Galsky Matthew, MD,PhD, matthew.galsky@mssm.edu
Galsky Matthew, MD,PhD
China1 site, 1 recruiting
- Recruiting
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, 201203
Dingwei Ye, MD,PhD, +8602164175590
Dingwei Ye, MD,PhD
About this study
Official title: A Phase I/II Open-Label Multicenter Study to Evaluate the Safety and Efficacy of Oral APL-1202 in Combination With Tislelizumab Compared to Tislelizumab Alone as Neoadjuvant Therapy in Patients With Muscle Invasive Bladder Cancer (MIBC)
This trial is designed to evaluate the safety, efficacy, and biomarker response of APL-1202 in combination with tislelizumab as neoadjuvant therapy for patients with MIBC who are cisplatin ineligible or refuse cisplatin-based chemotherapy.
Read the detailed description
This trial is an open-label, multi-center clinical study consisting of two periods: Phase Ⅰ and Phase Ⅱ. Phase I is a dose escalation study to determine MTD (maximum tolerated dose) and/or RP2D. Phase II is an expanded proof of concept (POC) study to evaluate the safety and efficacy of APL-1202 in combination with tislelizumab compared to tislelizumab alone as neoadjuvant therapy for MIBC as measured by pCR.
Phase Ⅰ and Phase Ⅱ both are divided into 3 periods: screening period, neoadjuvant therapy and follow-up period:
- The screening period is up to 4 weeks before the first doses of study treatments.
- During the neoadjuvant therapy, each patient will receive the combined treatment of tislelizumab and APL-1202 or tislelizumab alone, every 21 days as a dosing cycle for a total of 3 cycles of treatment prior to radical cystectomy.
- The follow-up period includes a safety follow-up at 4 weeks after radical cystectomy.
Phase Ⅰ: Dose-Escalation The dose escalation phase will assess the safety, tolerability, and pharmacokinetics of APL-1202 in combination with tislelizumab in MIBC patients. Results from this period will determine the RP2D of APL-1202 in combination with tislelizumab as neoadjuvant therapy for MIBC.
Patients enrolled in this phase must meet the following criteria: those with newly diagnosed MIBC for whom RC is planned, and who are cisplatin ineligible or refuse to receive cisplatin based neoadjuvant chemotherapy, and with calculated CrCl ≥ 50 mL/min (by Cockcroft-Gault equation).
A standard 3+3 dose-escalation design will be used. The dose of APL-1202 will start at 375 mg (125 mg, TID) and increase sequentially to 750 mg (250 mg, TID) and 1,125 mg (375 mg, TID). For more information on the dose escalation design, please see the Dose Escalation Criteria section.
Table 1: Dose-Escalation plan
Dose Level Tislelizumab APL-1202 Patients (n)
- 200 mg, IV, Q3w 125 mg, PO, TID ≥ 3
- 200 mg, IV, Q3w 250 mg, PO, TID ≥ 3
- 200 mg, IV, Q3w 375 mg, PO, TID ≥ 3 Patients will be assigned to one of three APL-1202 dose levels. Each patient will receive 3 cycles of treatment prior to RC and each cycle is 3 weeks. On day 1 of each cycle, a single dose of 200 mg tislelizumab will be administered intravenously and APL-1202 will be administered orally TID daily for 3 weeks. If the dose level 1 is determined to be safe and tolerable, 3 patients will be enrolled to Dose Level 2 and will receive their treatments in 3-week treatment cycles and safety will be assessed. This process is repeated one more time for the Dose Level 3.
The DLT observation window for any dose level will be treatment cycle 1 (1-21 days).
Patients who do not complete the DLT observation period (cycle 1) will be replaced unless the discontinuation of treatment is DLT-related.
DLT assessment will be performed during the first cycle (1-21 days) of study treatments. An evaluable patient is defined as a patient who has received at least 75% of planned APL-1202 doses during the first cycle of treatment and completed all the safety evaluations required for the first cycle, or any patient who has DLT during the first cycle. If a patient receives less than 75% of planned APL-1202 doses during the first cycle or withdraws from the study due to reasons other than DLT, the patient will be replaced.
There will be no intra-patient dose escalation. A patient will receive treatments of cycle 2 and cycle 3 or until unacceptable toxicity, disease progression, or discontinuation for any other reason.
Phase Ⅱ: Proof of Concept (POC) The primary objective of this phase is to evaluate the safety and efficacy of APL-1202 in combination with tislelizumab compared to tislelizumab alone as neoadjuvant therapy for MIBC as measured by pathologic complete response (pCR).
Patients enrolled in this phase must meet the following criteria: those with newly diagnosed MIBC for whom RC is planned, and who are cisplatin ineligible or refuse to receive cisplatin based neoadjuvant chemotherapy.
As shown in Figure 1 below, eligible patients will be randomly assigned to group 1 or group 2, with PD-L1expression level as a stratification factor. For those assigned to group 1, each patient will receive 3 cycles of treatment prior to RC and each cycle is 3 weeks. On day 1 of each cycle, a single dose of 200 mg tislelizumab will be administered intravenously. APL-1202 will be administered orally TID daily for 3 weeks at the RP2D defined from Phase I. For patients assigned to group 2, each patient will receive 3 cycles of treatments with a single dose of 200 mg tislelizumab administered on day 1 of each cycle, followed by RC. A patient will stay on treatment until completion of planned treatments, unacceptable toxicity, disease progression, or discontinuation for any other reason.
In this period, patients with renal function with calculated CrCl ≥ 30 mL/min (by Cockcroft-Gault equation) will be recruited. if patients with CrCl ≥ 50 mL/min, start dose of APL-1202 is recommended to be RP2D defined from Phase I; for patients with CrCl 30-50 mL/min, the dose of APL-1202 is recommended to be reduced by 1 dose level from RP2D defined from Phase I (from 1125 mg/day to 750 mg/day, or from 750 mg/day to 375 mg/day).
- Conditions
- Muscle Invasive Bladder Cancer
- Being tested
- APL-1202 in combination with tislelizumab, Tislelizumab alone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APL-1202 in combination with tislelizumabDrug
For those assigned to this group (1), each patient will receive 3 cycles of treatment prior to RC and each cycle is 3 weeks. On day 1 of each cycle, a single dose of 200 mg tislelizumab will be administered intravenously. APL-1202 will be administered orally TID daily for 3 weeks at the RP2D defined from Phase I.
Tislelizumab aloneDrug
For patients assigned to this group (2), each patient will receive 3 cycles of treatments with a single dose of 200 mg tislelizumab administered on day 1 of each cycle, followed by RC.
| Study group | Role | What they receive |
|---|---|---|
| APL-1202 in combination with tislelizumab | Active comparator | Not described Receives: Drug: APL-1202 in combination with tislelizumab |
| Tislelizumab alone | Placebo comparator | Not described Receives: Drug: Tislelizumab alone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events (AE) and serious adverse events (SAE).
Adverse events (AE) and serious adverse events (SAE) in Phase Ⅰ(Dose-Escalation)
Measured: 9 weeks
The RP2D of APL-1202 in combination with tislelizumab.
The RP2D of APL-1202 in combination with tislelizumab in Phase Ⅰ(Dose-Escalation)
Measured: 9 weeks
The rate of pathologic complete response (pCR) in Phase 2.
Pathological complete response (pCR) is defined as no microscopic evidence of residual disease in the bladder based on histological evaluation of the resected bladder specimen collected during cystectomy.
Measured: 26 months
Secondary outcomes (11)
Radiological response (RR).
CT or MRI scan taken at screening and pre-radical cystectomy visits. Response will be evaluated using standard RECIST 1.1 criteria.
Measured: 26 months
Cmax
PK parameters of APL-1202 expressed as Cmax when administered concurrently with tislelizumab.
Measured: 26 months
Tmax
PK parameters of APL-1202 expressed as Tmax when administered concurrently with tislelizumab.
Measured: 26 months
t1/2
PK parameters of APL-1202 expressed as t1/2 when administered concurrently with tislelizumab.
Measured: 26 months
AUC
PK parameters of APL-1202 expressed as AUC when administered concurrently with tislelizumab.
Measured: 26 months
Cumulative amount in urinary excretion (Ae)
PK parameters of APL-1202 expressed as Ae when administered concurrently with tislelizumab.
Measured: 26 months
cumulative fraction of dose in urinary excretion (Ae%)
PK parameters of APL-1202 expressed as Ae% when administered concurrently with tislelizumab.
Measured: 26 months
Tumor mutation burdens (TMB) in pre- and post-treatment plasma ctDNA (circulating tumor DNA).
Plasma circulating tumor DNA (ctDNA) were extracted from the patients before and after treatment; somatic mutations were detected by targeted region sequencing. Tumor mutation burdens (TMB) was calculated by mutations per million sequenced bases.
Measured: 26 months
Tumor mutation burdens (TMB) in pre- and post-treatment urine cfDNA (cell free DNA).
Urine cell free DNA (cfDNA) were extracted from the patients before and after treatment; somatic mutations were detected by targeted region sequencing. Tumor mutation burdens (TMB) was calculated by mutations per million sequenced bases.
Measured: 26 months
Tumor mutation burdens (TMB) in pre- and post-treatment tumor tissues.
Tumor tissue FFPE slides were collected from the patients before and after treatment. DNA was extracted from the FFPE slides. Somatic mutations were detected by targeted region sequencing. Tumor mutation burdens (TMB) was calculated by mutations per million sequenced bases.
Measured: 26 months
PD-L1 protein expression levels in pre- and post-treatment tumor tissues.
Tumor tissue FFPE slides were collected from the patients before and after treatment. PD-L1 protein expression levels were evaluated by IHC (immunohistochemistry, VENTANA PD-L1/SP263 Assay).
Measured: 26 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2021
- Study start28 Dec 2021
- Primary completion1 Nov 2023 (estimated)
- Study completion1 Mar 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Muscle Invasive Bladder 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 79 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jiangsu Yahong Meditech Co., Ltd aka Asieris
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04813107
- Sponsor's protocol ID
- YHGT-NP-01
- Acronym
- ANTICIPATE
- Status last verified
- Feb 2022
- First submitted
- 21 Mar 2021
- Last updated
- 22 Feb 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Open-Label Multicenter Study to Evaluate the Safety and Efficacy of Oral APL-1202 in Combination With Tislelizumab Compared to Tislelizumab Alone as Neoadjuvant Therapy in Patients With Muscle Invasive Bladder Cancer (MIBC)
- ClinicalTrials.gov ID
- NCT04813107
- Acronym / sponsor ID
- ANTICIPATE / YHGT-NP-01
- Conditions
- Muscle Invasive Bladder Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 79 participants (estimated)
- Lead sponsor
- Jiangsu Yahong Meditech Co., Ltd aka AsierisIndustry (pharma, biotech, devices)
- Study start
- 28 Dec 2021 (actual)
- Primary completion
- 1 Nov 2023 (estimated)
- Study completion
- 1 Mar 2024 (estimated)
- First posted
- 24 Mar 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.
This trial is designed to evaluate the safety, efficacy, and biomarker response of APL-1202 in combination with tislelizumab as neoadjuvant therapy for patients with MIBC who are cisplatin ineligible or refuse cisplatin-based chemotherapy.
Detailed description
This trial is an open-label, multi-center clinical study consisting of two periods: Phase Ⅰ and Phase Ⅱ. Phase I is a dose escalation study to determine MTD (maximum tolerated dose) and/or RP2D. Phase II is an expanded proof of concept (POC) study to evaluate the safety and efficacy of APL-1202 in combination with tislelizumab compared to tislelizumab alone as neoadjuvant therapy for MIBC as measured by pCR.
Phase Ⅰ and Phase Ⅱ both are divided into 3 periods: screening period, neoadjuvant therapy and follow-up period:
- The screening period is up to 4 weeks before the first doses of study treatments.
- During the neoadjuvant therapy, each patient will receive the combined treatment of tislelizumab and APL-1202 or tislelizumab alone, every 21 days as a dosing cycle for a total of 3 cycles of treatment prior to radical cystectomy.
- The follow-up period includes a safety follow-up at 4 weeks after radical cystectomy.
Phase Ⅰ: Dose-Escalation The dose escalation phase will assess the safety, tolerability, and pharmacokinetics of APL-1202 in combination with tislelizumab in MIBC patients. Results from this period will determine the RP2D of APL-1202 in combination with tislelizumab as neoadjuvant therapy for MIBC.
Patients enrolled in this phase must meet the following criteria: those with newly diagnosed MIBC for whom RC is planned, and who are cisplatin ineligible or refuse to receive cisplatin based neoadjuvant chemotherapy, and with calculated CrCl ≥ 50 mL/min (by Cockcroft-Gault equation).
A standard 3+3 dose-escalation design will be used. The dose of APL-1202 will start at 375 mg (125 mg, TID) and increase sequentially to 750 mg (250 mg, TID) and 1,125 mg (375 mg, TID). For more information on the dose escalation design, please see the Dose Escalation Criteria section.
Table 1: Dose-Escalation plan
Dose Level Tislelizumab APL-1202 Patients (n)
- 200 mg, IV, Q3w 125 mg, PO, TID ≥ 3
- 200 mg, IV, Q3w 250 mg, PO, TID ≥ 3
- 200 mg, IV, Q3w 375 mg, PO, TID ≥ 3 Patients will be assigned to one of three APL-1202 dose levels. Each patient will receive 3 cycles of treatment prior to RC and each cycle is 3 weeks. On day 1 of each cycle, a single dose of 200 mg tislelizumab will be administered intravenously and APL-1202 will be administered orally TID daily for 3 weeks. If the dose level 1 is determined to be safe and tolerable, 3 patients will be enrolled to Dose Level 2 and will receive their treatments in 3-week treatment cycles and safety will be assessed. This process is repeated one more time for the Dose Level 3.
The DLT observation window for any dose level will be treatment cycle 1 (1-21 days).
Patients who do not complete the DLT observation period (cycle 1) will be replaced unless the discontinuation of treatment is DLT-related.
DLT assessment will be performed during the first cycle (1-21 days) of study treatments. An evaluable patient is defined as a patient who has received at least 75% of planned APL-1202 doses during the first cycle of treatment and completed all the safety evaluations required for the first cycle, or any patient who has DLT during the first cycle. If a patient receives less than 75% of planned APL-1202 doses during the first cycle or withdraws from the study due to reasons other than DLT, the patient will be replaced.
There will be no intra-patient dose escalation. A patient will receive treatments of cycle 2 and cycle 3 or until unacceptable toxicity, disease progression, or discontinuation for any other reason.
Phase Ⅱ: Proof of Concept (POC) The primary objective of this phase is to evaluate the safety and efficacy of APL-1202 in combination with tislelizumab compared to tislelizumab alone as neoadjuvant therapy for MIBC as measured by pathologic complete response (pCR).
Patients enrolled in this phase must meet the following criteria: those with newly diagnosed MIBC for whom RC is planned, and who are cisplatin ineligible or refuse to receive cisplatin based neoadjuvant chemotherapy.
As shown in Figure 1 below, eligible patients will be randomly assigned to group 1 or group 2, with PD-L1expression level as a stratification factor. For those assigned to group 1, each patient will receive 3 cycles of treatment prior to RC and each cycle is 3 weeks. On day 1 of each cycle, a single dose of 200 mg tislelizumab will be administered intravenously. APL-1202 will be administered orally TID daily for 3 weeks at the RP2D defined from Phase I. For patients assigned to group 2, each patient will receive 3 cycles of treatments with a single dose of 200 mg tislelizumab administered on day 1 of each cycle, followed by RC. A patient will stay on treatment until completion of planned treatments, unacceptable toxicity, disease progression, or discontinuation for any other reason.
In this period, patients with renal function with calculated CrCl ≥ 30 mL/min (by Cockcroft-Gault equation) will be recruited. if patients with CrCl ≥ 50 mL/min, start dose of APL-1202 is recommended to be RP2D defined from Phase I; for patients with CrCl 30-50 mL/min, the dose of APL-1202 is recommended to be reduced by 1 dose level from RP2D defined from Phase I (from 1125 mg/day to 750 mg/day, or from 750 mg/day to 375 mg/day).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| APL-1202 in combination with tislelizumab | Active comparator | Drug: APL-1202 in combination with tislelizumab |
| Tislelizumab alone | Placebo comparator | Drug: Tislelizumab alone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Willing and able to provide written informed consent.
- Age ≥ 18 years.
- Histopathologically confirmed transitional cell carcinoma of the bladder. Patients with mixed histologies are required to have a dominant (i.e. > 50%) transitional cell pattern.
- Radical cystectomy is planned (according to local guidelines).
- Patients who refuse neoadjuvant cisplatin based chemotherapy or in whom neoadjuvant cisplatin based therapy is contraindicated. Contraindications to cisplatin is defined by meeting at least one of the following criteria:
Key exclusion criteria (26 listed)
- Previous systemic therapy for bladder cancer.
- Malignancies other than urothelial bladder cancer within 5 years prior to cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ of breast treated surgically with curative intent).
- Evidence of measurable nodal or metastatic disease.
- Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome).
- Pregnant female patients. All female patients with a positive pregnancy test within 2 weeks prior to the first dose of study treatment will be excluded from the study.
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 |
|---|---|---|
| APL-1202 in combination with tislelizumabFor those assigned to this group (1), each patient will receive 3 cycles of treatment prior to RC and each cycle is 3 weeks. On day 1 of each cycle, a single dose of 200 mg tislelizumab will be administered intravenously. APL-1202 will be administered orally TID daily for 3 weeks at the RP2D defined from Phase I. | Drug | APL-1202 in combination with tislelizumab |
| Tislelizumab aloneFor patients assigned to this group (2), each patient will receive 3 cycles of treatments with a single dose of 200 mg tislelizumab administered on day 1 of each cycle, followed by RC. | Drug | Tislelizumab alone |
Primary outcome
Adverse events (AE) and serious adverse events (SAE).
Time frame: 9 weeks
Adverse events (AE) and serious adverse events (SAE) in Phase Ⅰ(Dose-Escalation)
The RP2D of APL-1202 in combination with tislelizumab.
Time frame: 9 weeks
The RP2D of APL-1202 in combination with tislelizumab in Phase Ⅰ(Dose-Escalation)
The rate of pathologic complete response (pCR) in Phase 2.
Time frame: 26 months
Pathological complete response (pCR) is defined as no microscopic evidence of residual disease in the bladder based on histological evaluation of the resected bladder specimen collected during cystectomy.
11 secondary outcomes
Radiological response (RR).
Time frame: 26 months
Cmax
Time frame: 26 months
Tmax
Time frame: 26 months
t1/2
Time frame: 26 months
AUC
Time frame: 26 months
Cumulative amount in urinary excretion (Ae)
Time frame: 26 months
cumulative fraction of dose in urinary excretion (Ae%)
Time frame: 26 months
Tumor mutation burdens (TMB) in pre- and post-treatment plasma ctDNA (circulating tumor DNA).
Time frame: 26 months
Tumor mutation burdens (TMB) in pre- and post-treatment urine cfDNA (cell free DNA).
Time frame: 26 months
Tumor mutation burdens (TMB) in pre- and post-treatment tumor tissues.
Time frame: 26 months
PD-L1 protein expression levels in pre- and post-treatment tumor tissues.
Time frame: 26 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2022.
- 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.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing APL-1202 in combination with tislelizumab and Tislelizumab alone in people with Muscle Invasive Bladder Cancer, run by Jiangsu Yahong Meditech Co., Ltd aka Asieris at 2 sites in 2 countries.
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 22 inclusion and 26 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 22 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, 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. Some participants in this study may receive a placebo. 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 Mingming Zhang, MD (+8613816002336, mmzhang@asieris.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse events (AE) and serious adverse events (SAE). (time frame: 9 weeks). 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 22 Feb 2022; AzTrials last refreshed its copy on 7 Nov 2026.