C3 STAR-C

Tumour infiltration lymphocyte (TIL) immunotherapy is a cutting edge personalized therapy that has shown promising results in BTC patients. However, in Canada, TIL immunotherapy is underdeveloped and underutilized largely owing to the lack of infrastructure available to produce TILs and administer them. This is why the C3 has mandated to develop and push forward TIL immunotherapy so that it can be offered to BTC patients in Canada. We will conduct a prospective, open-label, two-center, non-randomized, Phase 1b study looking at the feasibility, safety, efficacy, and biologic features of autologous PD-1+-selected TIL combined with IL-2 and anti-PD-L1 following lymphodepletion administered in metastatic cholangiocarcinoma patients refractory to at least one line of any standard systemic treatment. Durvalumab will be administered for one year starting 2 weeks after PD-1+-selected TIL administration, to promote transfused TIL efficacy. Tumor harvest for TIL manufacturing and cryopreservation will be allowed at any time point during standard of care treatment (e.g. before or during a pause in standard systemic treatment or upon progression). TIL will be administered only upon evidence of progression or intolerance to first or subsequent lines of standard treatment. The target number of patients for TIL administration is 15 overall for both sites (The Ottawa Hospital and CHUM). For the initiation of this trial, TIL manufacturing will be performed at one site, in the CHUM clean room facility; tumors harvested in Ottawa will be shipped to the CHUM manufacturing facility as per standard procedures currently widely used in TIL multicenter trials with centralized manufacturing. One of our goals is to expand TIL manufacturing to other sites in Canada. We will carry out technology transfer and once the Ottawa site has successfully adopted the CHUM manufacturing process, an amendment for the trial will be sent to Health Canada to allow manufacturing in Ottawa.