Phase Ib/II Study to Evaluate the Safety and Efficacy of Nivolumab in Combination With Paclitaxel in Epstein-Barr Virus(EBV)-Related, or Microsatellite Instability-High (MSI-H), or Programmed Cell Death Ligand 1 (PD-L1) Positive Advanced Gastric Cancer

Yonsei University

Status and phase

Completed

Phase 2

Phase 1

Conditions

Recurrent/Metastatic Gastric Cancer

Treatments

Drug: Nivolumab, Paclitaxel

Study type

Interventional

Funder types

Other

Identifiers

NCT05535569

4-2017-0277

Details and patient eligibility

About

This is a Phase Ib/II study to identify the recommended dose of paclitaxel and nivolumab for further study, and to assess the safety and clinical efficacy of this combined treatment in EBV-related, MSI-high, or PD-L1 positive advanced gastric cancer after first line treatment.

Full description

Patients who are EBV-related, MSI-high, or PD-L1 positive will be confirmed by immunohistochemistry (IHC) in a central laboratory (Yonsei Cancer Center), and who meet all eligibility criteria will be enrolled to this study and receive treatment with nivolumab and paclitaxel until progressive disease is confirmed or at least 1 discontinuation criterion is met. It was assumed that about 15% of screened patients will be categorized EBV-related, MSI-high, or PD-L1 positive gastric cancer based on previously reported study results. Part 1>> Phase Ib Phase Ib: 6-12 (The actual number of subjects will be determined by the number of dose escalations to identify MTD and RP2D) Part 2>> Phase II - At the RP2D dose level in phase I part, we will expand phase 2 study for a total of 50 patients. Patients will be treated until the time of disease progression, intolerable toxicities, patient's refusal or consent withdrawal. Tumor assessment will be done every 6 weeks.

Enrollment

50 patients

Sex

All

Ages

19+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Has provided digned written informed Consent
Is male or female ≥19 years of age
Has a histologically or cytologically confirmed diagnosis of advanced gastric adenocarcinoma
Has documented EBV-related, MSI-high, or PD-L1 positive tumor in primary or metastatic tumor tissue
Has a life expectancy of at least 3 months
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Has measurable or evaluable disease as determined by RECIST 1.1.
Is able to swallow and retain orally administered medication
Has an adequate baseline organ function defined as:
- White blood cells ≥3000/mm3 and neutrophils ≥1500/mm3
- Platelets ≥100000/mm3
- Hemoglobin ≥9.0 g/dL
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 × upper limit of normal (ULN) of the study site (or ≤5.0 × ULN in patients with liver metastases)
- Total bilirubin ≤2.0 × ULN
- Creatinine≤1.5 × ULN or creatinine clearance (either measured value or estimated value using the Cockcroft-Gault equation) >60ml/min.

Exclusion criteria

Has HER2-positive or indeterminate gastric cancer
Have multiple cancers
Have a current or past history of severe hypersensitivity to any other antibody products
Have concurrent autoimmune disease or a history of chronic or recurrent autoimmune disease
Have a current or past history of interstitial lung disease or pulmonary fibrosis diagnosed based on imaging (preferably CT) or clinical findings
Have brain or meninx metastases. Patients may be randomized for the study if they are asymptomatic and require no treatment.
Have pericardial fluid, pleural effusion, or ascites requiring treatment
Have a history of uncontrollable or significant cardiovascular disease
Have systemic infection requiring treatment
Are contraindicated for paclitaxel
Has had prior treatment with:
- Require or, within 28 days before treatment, have received systemic corticosteroids or immunosuppressants
Have undergone surgery (any surgery involving general anesthesia) within 28 days before study treatment
Have received radiotherapy for gastric cancer within 28 days before treatment or radiotherapy for bone metastases within 14 days before treatment
Have a positive test result for human immunodeficiency virus-1 (HIV-1) antibody,
Hepatitis B surface protein (HBs) antigen and HBV titer >2000 IU/ml (10,000 copy/ml), or hepatitis C virus (HCV) antibody positive result
Are pregnant or breastfeeding, or possibly pregnant
Has any unresolved ≥Grade 2 (per CTCAE v4.0) toxicity from previous anti-cancer therapy at the time of enrollment such as neuropathy, except alopecia or anemia
Have previously received nivolumab, anti-programmed cell death-1 (PD-1) antibody, anti-PD-L1 antibody, anti-programmed cell death-ligand 2 (PD-L2) antibody, anti-CD137 antibody, anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody, or other therapeutic antibodies or pharmacotherapies for the regulation of T-cells
Are incapable of providing consent for specific reasons, such as concurrent dementia
Are otherwise inappropriate for this study in the investigator's or subinvestigator's opinion.