A Prospective, Randomized, Multicenter, Comparative Study of the Efficacy of Imatinib Resumption Combined With Atezolizumab Versus Imatinib Resumption Alone in Patients With Unresectable Advanced Gastrointestinal Stromal Tumors (GIST) After Failure of Standard Treatments (ATEZOGIST)

A Prospective, Randomized, Multicenter, Comparative Study of the Efficacy of Imatinib Resumption Combined With Atezolizumab Versus Imatinib Resumption Alone in Patients With Unresectable Advanced Gastrointestinal Stromal Tumors (GIST) After Failure of Standard Treatments (ATEZOGIST)

Gastrointestinal Stromal Tumor

Recruiting

2

Start Date 01/14/2022

Age of Trial (yrs) 2.3

Gleevec-resistant

KIT/PDGFRA inhibitor + PD-L1 inhibitor

Block KIT + Unblock cell death genes

Specifically GIST and only GIST

ET19-075- ATEZOGIST

Centre Leon Berard

Julien GAUTIER +33 4 26 55 68 29 julien.gautier@lyon.unicancer.fr

Randomized

Oral Intravenous

Brief Summary:

This trial is a prospective, randomized (1:1 ratio), multicenter, comparative and phase II study, conducted in patients with unresectable advanced gastrointestinal stromal tumors (GIST) after failure of imatinib (disease progression),sunitinib and regorafenib (either disease progression or intolerance)

Partial Criteria (see clincaltrials.gov listing for full criteria)

Partial INCLUSION CRITERIA : (see clincaltrials.gov listing for full criteria)

I1. Male or female ≥ 18 years at the day of consenting to the study;

I2. Patients must have histologically confirmed diagnosis of GIST (within the French Reference Network in Pathology of Sarcomas - RRePS network); archival tumor sample must be made available for translational research program (in case there is no sufficient archival tumor material available, a biopsy must be performed prior to treatment start); Nota Bene: mutational status and level of expression of PD1/PD-L1 will not be considered as selection criteria but will be studied as endpoints for translational objectives.

I3. Locally advanced or metastatic disease confirmed as measurable according to the RECIST V1.1 (Appendix 1);

I4. Patients who previously failed to at least imatinib, sunitinib and then regorafenib. Failure is defined for Imatinib as progressive disease, and for sunitinib and regorafenib as progressive disease and/or intolerance;

I5. Performance Status of the ECOG of 0 or 1;

In the first arm, patients will be treated with imatinib + atezolizumab (experimental arm), whereas in the second arm, patients will be treated with imatinib alone (control arm).

The comparison between this two arms will allow to compare whether or not atezolizumab and imatinib is efficient for disease control, in terms of Progression-Free Survival improvement.

Partial EXCLUSION CRITERIA : (see clincaltrials.gov listing for full criteria)

E1. Prior malignancy within the last 3 years except for locally curable disease with no sign of relapse;

E2. Patients in whom imatinib had been already reintroduced after sunitinib as second line;

E3. Known D842V mutation in Exon 18 of PDGFRA;

E4. Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-cytotoxic T lymphocyte-associated protein 4 , anti-TIGIT, anti PD-1,and anti PD-L1 therapeutic antibodies;