Tislelizumab in Combination With Bevacizumab and Capecitabine in Advanced Solid Tumors With Evaluation in Immunotherapy-Resistant and Central Nervous System Disease

NCT07681297 | Not Yet Recruiting Phase 1

• 2 other identifiers: BR01/01/262026-0764
• Study Type: interventional
• Target: 154
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to establish the safety of the combination of PD-1 inhibitor tislelizumab, an anti-angiogenic agent bevacizumab and a chemotherapeutic agent capecitabine, in a phase Ib setting and to evaluate preliminary efficacy in selected expansion cohorts, including PD-L1-negative metastatic triple negative breast cancer (TNBC) and patients with active CNS disease. A sequential approach to cohort expansion will allow further evaluation in hormone receptor positive (HR+), HER2 negative (HER2-) disease if a signal of activity is observed in PD-L1 negative TNBC.

Conditions

Advanced Solid Tumor Cancer; Triple-Negative Breast Cancer (TNBC); CNS Disease; Breast Cancer

Keywords

Tislelizumab; Bevacizumab; Capecitabine; Breast Cancer; Advanced Solid Tumour Cancer; CNS disease; Triple-Negative Breast Cancer (TNBC)

Outcome Measures

Primary Outcomes (5)

• Phase Ib: Number and percentage of participants with treatment-related adverse events as assessed by CTCAE v5.0

  2 years

• Phase Ib: Phase II recommended dose of capecitabine in combination with tislelizumab and bevacizumab

  2 years

• Phase II TNBC Cohort: 12-month progression-free survival rate with tislelizumab, bevacizumab and capecitabine

  12 months

• Phase II CNS Cohort: Intracranial objective response rate with tislelizumab, bevacizumab and capecitabine

  2 years

• Phase II HR-positive/HER2-negative Cohort (if activated): 12-month progression-free survival rate with tislelizumab, bevacizumab, and capecitabine.

  12 months

Secondary Outcomes (11)

• Phase Ib: Incidence and severity of adverse events (AEs), including serious adverse events (SAEs) and immune-related adverse events (irAEs)

  2 years

• Phase II (TNBC, HR+/HER2- MBC): Objective response rate (ORR)

  2 years

• Phase II (TNBC, HR+/HER2- MBC): Disease control rate (DCR)

  2 years

• Phase II (TNBC, HR+/HER2- MBC): Duration of response (DoR)

  2 years

• Phase II (TNBC, HR+/HER2- MBC): Median progression-free survival (PFS)

  2 years

Other Outcomes (5)

• All Phases and Cohorts: Association between tumor genetic biomarkers and treatment response (ORR, DCR, PFS)

  2 years

• All Phases and Cohorts: Association between tumor immunohistochemistry biomarkers and treatment response (ORR, DCR, PFS)

  2 years

• All Phases and Cohorts: Association between plasma protein biomarkers and treatment response (ORR, DCR, PFS)

  2 years

Study Arms (4)

Phase Ib: Dose-Finding / Safety Confirmation

EXPERIMENTAL

Patients with advanced solid tumors will be enrolled into a standard 3+3 design. Dose escalation will proceed using two predefined dose levels (DL1 and DL-1). There will be no dose reductions permitted for either tislelizumab or bevacizumab; dose modifications, if required, will apply only to capecitabine in accordance with protocol-defined guidelines. If the DL-1 dose level is not tolerated, further dose de-escalation is not pre-specified. In such a scenario, a formal review will be undertaken in consultation with the Study's Scientific Committee to determine the appropriate next steps, including consideration of additional dose reduction strategies or discontinuation of further dose exploration for the combination.

Drug: Tislelizumab + Bevacizumab + Capecitabine

Phase II: Multi-Cohort Expansion - PD-L1 negative TNBC cohort

EXPERIMENTAL

Drug: Tislelizumab + Bevacizumab + Capecitabine

Phase II: Multi-Cohort Expansion - Active CNS disease cohort

EXPERIMENTAL

Drug: Tislelizumab + Bevacizumab + Capecitabine

Phase II: Multi-Cohort Expansion - HR+/HER2- MBC cohort

EXPERIMENTAL

Drug: Tislelizumab + Bevacizumab + Capecitabine

Interventions

Tislelizumab + Bevacizumab + Capecitabine DRUG

Phase Ib Dose Levels Dose Level DL1 (Starting Dose) * Tislelizumab: 200 mg IV Day 1 q3w * Bevacizumab: 7.5 mg/kg IV Day 1 q3w * Capecitabine: 1000 mg/m² PO BID Days 1-14 q3w DL-1 (De-escalation) * Tislelizumab: 200 mg IV Day 1 q3w * Bevacizumab: 7.5 mg/kg IV Day 1 q3w * Capecitabine: 800 mg/m² PO BID Days 1-14 q3w

Phase II: Multi-Cohort Expansion - Active CNS disease cohort; Phase II: Multi-Cohort Expansion - HR+/HER2- MBC cohort; Phase II: Multi-Cohort Expansion - PD-L1 negative TNBC cohort; Phase Ib: Dose-Finding / Safety Confirmation

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 21 years or older at the time of informed consent.
• Histologically or cytologically confirmed advanced or metastatic solid tumor.
• Patients must have received at least one prior line of standard systemic therapy for locally advanced/unresectable or metastatic disease, OR be ineligible for, intolerant of, or have declined standard-of-care therapy, with the specific reason documented in the source records.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Estimated life expectancy of at least 12 weeks.
• At least one evaluable (measurable or non-measurable) lesion as defined by RECIST version 1.1, unless otherwise specified for a disease-specific cohort.
• Recovery to Grade 1 or baseline from acute toxicities of prior anti-cancer therapy, except for alopecia, vitiligo, or other toxicities deemed not clinically significant by the investigator.
• Adequate organ and marrow function within 14 days prior to first dose of study treatment, defined as follows:
• Absolute neutrophil count ≥1.5 × 10\^9/L
• Platelet count ≥100 × 10\^9/L
• Haemoglobin ≥9.0 g/dL
• Total bilirubin \<1.5 × upper limit of normal, except in patients with known Gilbert's syndrome, in whom total bilirubin up to 3.0 × upper limit of normal is permitted provided direct bilirubin is within normal limits
• AST and ALT \<2.5 × upper limit of normal, or \<5 × upper limit of normal in the presence of liver metastases
• Calculated creatinine clearance ≥50 mL/min (calculated using the Cockcroft-Gault formula)
• Urine protein dipstick \<2+, or if urine dipstick is 2+ or greater, 24-hour urine protein \<1 g per 24 hours

You may not qualify if:

• Treatment with an investigational agent within 14 days prior to first dose of study treatment.
• Known hypersensitivity or contraindication to tislelizumab, bevacizumab, capecitabine, fluoropyrimidines, or any excipients of the study drugs.
• Known clinically significant dihydropyrimidine dehydrogenase deficiency.
• Uncontrolled or clinically unstable CNS disease, including poor performance status attributable to CNS disease, ongoing requirement for escalating corticosteroids, uncontrolled seizures, or rapid neurologic deterioration.
• Clinically significant cardiovascular disease, including uncontrolled hypertension, unstable angina, clinically significant arrhythmia, myocardial infarction, or stroke that is of clinical concern in the opinion of the investigator.
• Significant bleeding risk or recent clinically significant hemorrhage.
• History of gastrointestinal perforation, fistula, or intra-abdominal abscess within 6 months prior to first dose, or other conditions conferring high risk in the opinion of the investigator.
• Non-healing wound, active ulcer, or untreated fracture.
• Active infection requiring systemic therapy.
• Active autoimmune disease requiring systemic immunosuppressive treatment within the past 2 years, with exceptions such as replacement therapy or other conditions judged unlikely to recur.
• Current use of systemic immunosuppressive medication, excluding physiologic corticosteroid replacement or other permitted low-dose steroids.
• Active pneumonitis or interstitial lung disease requiring treatment, or other clinically significant pulmonary condition that, in the opinion of the investigator, would increase the risk of study treatment.
• Other active malignancy requiring treatment or likely to interfere with assessment of study endpoints, in the opinion of the investigator.
• Pregnancy or breastfeeding.
• Any serious medical, psychiatric, or social condition that, in the opinion of the investigator, would compromise patient safety, interfere with study participation, or confound interpretation of study results.

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (1)

National University Cancer Institute, Singapore, National University Health System

Singapore, Singapore

Location

Related Publications (2)

• Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012 Jun 28;366(26):2455-65. doi: 10.1056/NEJMoa1200694. Epub 2012 Jun 2.

  PMID: 22658128 BACKGROUND

• Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012 Jun 28;366(26):2443-54. doi: 10.1056/NEJMoa1200690. Epub 2012 Jun 2.

  PMID: 22658127 BACKGROUND

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Central Nervous System Diseases; Breast Neoplasms

Interventions

tislelizumab; Bevacizumab; Capecitabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Soo Chin Lee

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Soo Chin Lee

CONTACT

+6567724621; soo_chin_lee@nuhs.edu.sg

Study Design

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

Study Record Dates

• First Submitted: June 2, 2026
• First Posted: July 2, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: July 10, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)