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

NCT04813107 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: YHGT-NP-01
• Study Type: interventional
• Target: 79
• Locations: 2 countries
• Sites: 2

Brief 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.

Conditions

Muscle Invasive Bladder Cancer

Outcome Measures

Primary Outcomes (3)

• Adverse events (AE) and serious adverse events (SAE).

  Adverse events (AE) and serious adverse events (SAE) in Phase Ⅰ(Dose-Escalation)

  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)

  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.

  26 months

Secondary Outcomes (11)

• Radiological response (RR).

  26 months

• Cmax

  26 months

• Tmax

  26 months

• t1/2

  26 months

• AUC

  26 months

Study Arms (2)

APL-1202 in combination with tislelizumab

ACTIVE COMPARATOR

Drug: APL-1202 in combination with tislelizumab

Tislelizumab alone

PLACEBO COMPARATOR

Drug: Tislelizumab alone

Interventions

APL-1202 in combination with tislelizumab DRUG

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.

APL-1202 in combination with tislelizumab

Tislelizumab alone DRUG

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.

Tislelizumab alone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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;

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Jiangsu Yahong Meditech Co., Ltd aka Asieris: lead

Study Sites (2)

Mount Sinai Medical Center

New York, New York, 10001, United States

RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 201203, China

RECRUITING

MeSH Terms

Interventions

tislelizumab

Central Study Contacts

Mingming Zhang, MD

CONTACT

+8613816002336; mmzhang@asieris.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2021
• First Posted: March 24, 2021
• Study Start: December 28, 2021
• Primary Completion: November 1, 2023
• Study Completion: March 1, 2024
• Last Updated: February 22, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1); US (1)