VHIO17002

Basket of Baskets: A Modular, Open-label, Phase II, Multicentre Study To Evaluate Targeted Agents in Molecularly Selected Populations With Advanced Solid Tumours

  • Code NKI: M18BOB
  • Code firma: VHIO17002
  • Code clinicaltrials.gov: NCT03767075

Principal Investigator

Dr. F.L. Opdam

Drugs

Atezolizumab (anti-PDL1 antibody), futibatinib (FGFR inhibitor), amivantamab

Summary

The Global objective of this Basket of Basket study is to evaluate the antitumor activity of each matched therapies that will be evaluated through the study in small molecularly selected populations.

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).”

Read more on clinicaltrials.gov

Patient population

Tumor characteristics: POLE mutation, POLD1 mutation, Intermediate mutational burden (≥ 12-16 mutations/Mb), PDL-1 amplified, FGFR1-3 mutation, FGFR1-3 amplification, FGFR1+, FGFR2+.

Additional comments:

Module 1:

  • Part 1A: BRCA1 or BRCA2 mutations – closed
  • Part 1B: MLH1, MSH2, MSH6, or PMS2 mutations – closed
  • Part 1C: tumors with POLE mutation, POLD1 mutation – closed
  • Part 1D: hypermutated tumors – open
  • Part 1E: tumors with other mutations in DNA-repair genes – closed
  • Part 1F: tumors with amplified PDL1 – open
  • Part 1G: CDK12 mutation – open

Module 2:

  • Part 2A: FGFR1-3 mutation – closed
  • Part 2B: FGFR1-3 mutation, only VUS – open
  • Part 2C: FGFR1-3 amplification – open
  • Part 2D: FGFR1+, FGFR2+ – open

Module 3:

  • Part 3A: MET mutation, MET + – open
  • Part 3B: MET amplification – open
  • Part 3C: EGFR mutation – open