NCT04817826

TremelImumab aNd Durvalumab For the Non-operatIve Management (NOM) of MSI-high Resectable GC/GEJC.

TremelImumab aNd Durvalumab Combination For the Non-operatIve Management (NOM) of Microsatellite InstabiliTY (MSI)-High Resectable Gastric or Gastroesophageal Junction Cancer: The Multicentre, Single-arm, Multi-cohort, Phase II INFINITY Study.

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 31 (estimated)
• Sponsor: Gruppo Oncologico del Nord-Ovest · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

INFINITY is a Phase II, multicentre, single-arm, multi-cohort trial aimed at evaluating the activity and safety of the combination of tremelimumab and durvalumab as neoadjuvant (Cohort 1) and definitive (Cohort 2) treatment for MSI-high gastric/gastroesophageal juction cancer patients eligible for radical surgery.

Detailed description

This study will pre-screen approximately 310 patients, in order to enrol a total number of 31 patients, 18 in Cohort 1 and 13 in Cohort 2, across 25 Italian Centres. After central confirmation of MSI-high, dMMR and EBV-negative status, patients with resectable gastric or gastroesophageal junction cancer (Siewert II/III), categorized as cT≥2, any cN, M0 or any cT, cN1-3, M0 according to TNM classification 8th edition, will be enrolled and they will receive a pre-operative treatment with tremelimumab 300 mg single administration (day 1) and durvalumab 1500 mg Q4W for 3 cycles (day 1, 29 and 57). All patients will undergo a complete disease restaging with chest-abdomen-pelvis CT scan, 18-FDG PET/CT, EUS with biopsies and liquid biopsy. In Cohort 1, patients will undergo standard gastrectomy with D2 lymphadenectomy between weeks 15 and 18 from enrolment (at least six weeks after the last treatment administration), followed by an active follow-up every 12 weeks for two years and then a standard follow-up every six months until the end of the fifth year from surgery. In Cohort 2, patients with no evidence of complete clinical response (defined as absence of disease persistence at radiological imaging, liquid biopsy and EUS) will be treated as in Cohort 1. Patients with complete clinical response will undergo a non-operative management (NOM) and will start an active follow-up phase every 12 weeks for two years with chest-abdomen-pelvis CT with contrast, 18-FDG PET/TC, if clinically indicated by the Investigator, EUS with multiple random biopsies of the tumor site and FNA of clinically suspicious regional nodes and liquid biopsy, followed by standard follow-up every six months until the end of the fifth year. At any time during follow-up, in case of clinical suspicion or confirmation of residual gastric cancer, either at imaging, pathologically at tissue biopsies/cytological specimens or at ctDNA in liquid biopsy, the patients will undergo standard surgery according to the clinical practice at their Centre (subtotal/total gastrectomy with D2 lymphadenectomy). Enrolment in Cohort 2 will start only after the completion of enrolment in Cohort 1 and after the extensive evaluation of the final results of Cohort 1 regarding to all endpoints (including exploratory endpoints) and after potential amendment(s) on study design, eligibility criteria and study procedures requested by the Sponsor's Steering Committee and an Independent Data Monitoring Committee made of foreign experts, and after the approval of the Ethics Committee and the Italian Medicines Agency.

Conditions

• Gastric Cancer
• Microsatellite Instability

Interventions

Type	Name	Description
DRUG	Durvalumab	durvalumab 1500 mg Q4W for 3 cycles (day 1, 29 and 57).
DRUG	Tremelimumab	tremelimumab 300 mg single administration (day 1)

Timeline

• Start date: 2021-04-01
• Primary completion: 2025-04-30
• Completion: 2026-04-30
• First posted: 2021-03-26
• Last updated: 2025-06-10

Locations

1 site across 1 country: Italy