The objective of module 1 will be to determine the overall response rate by RECIST 1.1 of atezolizumab in several arms. Subjects will be separated into arms depending on the mutations of their tumour. All patients in genomically selected populations will receive atezolizumab 1200 mg IV every 3 weeks
Basket studies are a new sort of clinical studies to identify patients with the same kind of mutations and treat them with the same drug, irrespective of their specific cancer type. In basket studies, depending on the mutation types, patients are classified into “baskets”. Targeted therapies that block that mutation are then identified and assigned to baskets where patients are treated accordingly.
This protocol has two parts: part A (iPROFILER), which includes the common procedures for tumor molecular profiling and treatment recommendation, and part B (iBASKET), which corresponds to the therapeutic portion The purpose of part A (iPROFILER) of this study is to test participants’ tumour tissue in order to identify whether their tumour has certain mutations in cancer-related genes. It is known that gene mutations of tumours contribute to their origin and growth and determine whether the tumour will respond to particular cancer drugs. This test will provide information about potential targeted therapies that specifically attack those gene mutations. The purpose of part B (iBASKET) of this study is to offer participants a personalised anti-cancer treatment based on the gene mutations that are found in their tumour. Participants taking part in this module 1 of part B (iBASKET), in genomically selected populations, will receive atezolizumab 1200mg intravenously every 3 weeks, following the analysis of their tumour in part A (iPROFILER). Participants will be able to take atezolizumab for as long as their tumour doesn’t grow and for as long as they don’t have any side-effects which prevent them from continuing treatment.
The study will have a 2-year recruitment period. The aim of the study is to determine which genomically selected populations respond effectively to the targeted treatment, atezolizumab. Approximately 1000 participants will be enrolled into part A (iPROFILER), with approximately 100 participants being recruited into module 1 of part B (iBASKET).
What the MTBP does
Given a list of variants and the patient’s cancer type, the MTBP generates reports classifying their functional and predictive relevance for cancer.
The functionality of variants refers to their biological relevance for promoting disease phenotypes. This can inform –among others– the patient stratification to genomic-guided clinical trials (e.g. prioritize a FGFR inhibitor trial for those tumors with FGFR3 mutations estimated as activating) and the genetic counseling referral (e.g. if germline variants in cancer predisposing genes are estimated as pathogenic).
The predictive relevance of variants refers to their value for the disease diagnosis, prognosis and drug response according to the biomarkers reported by available clinical and preclinical studies. This analysis can reveal –among others– opportunities for investigational therapies or off-label prescriptions according to current knowledge.