Gastric Cancer
Conditions
Interventions
The current sub-protocol allows the patients to receive the following
combinations of study treatment:
1. Nivolumab + Ipilimumab: Nivolumab will be given at 1mg/kg in combination
with Ipilimumab 3mg
Sponsors
Bristol-Myers Squibb
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1) Participants must provide consent for 3 mandatory tumor biopsy samples (as detailed in*J* below). 2) All participants must have inoperable, advanced, or metastatic GC or GEJ carcinoma(including adenocarcinoma arising from the lower esophagus) and have histologically confirmed predominant adenocarcinoma. The documentation of GEJ involvement can include biopsy, endoscopy, or imaging. 3) Participants with human epidermal growth factor receptor 2 (HER2) overexpressing tumor who progress after trastuzumab (or are ineligible for or unwilling to be treated with trastuzumab) are eligible to be enrolled. 4) Prior adjuvant or neoadjuvant chemotherapy, radiotherapy, and/or chemoradiotherapy are permitted as long as the last administration of the last regimen (whichever was given last) occurred at least 4 weeks prior to randomization. 5) Participants must have an Eastern Cooperative Oncology Group performance status of <= 1 (see Appendix 7)., 6) Track-specific eligibility criteria Track 1: anti-PD-1, anti-PD-L1, and anti-CTLA-4 treatment-naïve participants 1).Participants must not have received any anti-PD-1, anti-PD-L1, or anti-CTLA-4 treatment prior to this study. Participants previously treated with agents other than anti-PD-1, anti-PD-L1, or anti-CTLA-4 are eligible for Track 1. 2).Participants may have been offered platinum-based chemotherapy for progressive or recurrent disease. 3).Participants must have documented PD-L1 tumor status following a required pretreatment biopsy as described below. After signing informed consent, participants will be required to submit a fresh tumor biopsy meeting the criteria defined above for IHC staining to determine PD-L1 status., Track 2: anti-PD-1, anti-PD-L1, or anti-CTLA-4 treatment-experienced participants 1).Participants must have had progressive or recurrent disease during or after anti-PD-1, anti-PD-L1, or anti-CTLA-4 treatment. (Participants treated with any study treatment targeting PD-1, PD-L1, or CTLA-4 will be considered anti-PD-1, anti-PD-L1, or anti-CTLA-4 treatment experienced, respectively) 2).Participants may have been offered a platinum-based chemotherapy for GC or GEJ. The platinum-based chemotherapy may have been in the adjuvant, neoadjuvant, or recurrent setting. 3).Participants who have had prior treatment with any 1 of the agents (or any other agent targeting PD-1, PD-L1, or CTLA-4) in monotherapy or in any combination regimen in a FRACTION-Gastric Cancer Sub-Protocol are eligible for treatment on Track 2. 4).Participants who have had prior combination treatment with the same IO combination agents (or IO agents directed against the same targets) as 1 of the combination regimens in a FRACTION-Gastric Cancer Sub-Protocol are eligible for study treatment on Track 2 but must be randomized to another combination regimen. 5).After signing informed consent, participants will be required to submit a fresh tumor biopsy for IHC staining to determine PD-L1 status., 7) At the time of screening, participants must have a life expectancy of at least 3 months following their most recent chemotherapy or immunotherapy for entry into all Tracks. a. Participants who wish to be re-randomized to a new study treatment combination on Track 2 following progression on a prior study treatment in Tracks 1 or 2 must have a li
Exclusion criteria
Exclusion criteria: a) Participants with overexpressing HER2 positive tumor and previously untreated with trastuzumab are excluded; participants who are ineligible for or unwilling to be treated with trastuzumab are still eligible. b) Participants with ascites that cannot be controlled with appropriate interventions. c) Participants must not have suspected, known, or progressive CNS metastases; have untreated CNS metastases; or have the CNS as the only site of disease. i) Participants are eligible if CNS metastases are adequately treated and participants neurologically return to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to study entry. In addition, participants mus tbe either off corticosteroids or on a stable or decreasing dose of prednisone 10 mg daily or equivalent) or other immunosuppressive medications within 14 days of study treatment administration. i) Inhaled or topical steroids and adrenal replacement steroid (prednisone > 10 mg daily or equivalent) are permitted in the absence of active autoimmune disease. j) Participants must not have a history of life-threatening toxicity related to prior IO treatment (eg, anti-CTLA-4 or anti-PD-1/PD-L1 treatment or any other antibody or treatment specifically targeting T-cell co-stimulation or immune checkpoint pathways). k) Participants must not have interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected treatment-related pulmonary toxicity. l) Participants must not have uncontrolled or significant cardiovascular disease including, but not limited to, any o
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To investigate the efficacy (by measuring Overall Response Rate, duration of response, and progression free survival rate at 24 weeks) of each treatment combination within the FRACTION study(as compared to Nivolumab in combination with Ipilimumab when applicable) in patients with advanced Gastric Cancer | — |
Secondary
| Measure | Time frame |
|---|---|
| To investigate the additional safety and tolerability of each study treatment combination in patients with advanced Gastric Cancer. Exploratory objectives: -To determine the pharmacodynamics effects of the medications by evaluating a selection of biomarkers in blood and tumour biopsy samples. -To assess the overall survival in treated patients -To explore the potential associations between anti-tumour activity or safety and select biomarker measures in tumor biopsy specimens and blood prior to study treatment and following drug administration. -To evaluation the pharmacokinetics of each investigational product. -To evaluate the immunogenicity of each investigational product. -To evaluate disease-related symptoms improvement using the GaCs in treated patients. -To evaluate general health using the EQ-5D in treated patients. | — |
Countries
Netherlands
Outcome results
None listed