An Open-label, Multi-centric, Phase I, Evaluating the Safety and the Efficacy of Combination of Atezolizumab, Tiragolumab and and Stereotactic Body Radiation Therapy in Patients With Oligometastatic Multiorgan (IMMUNOs-SBRT)

Centr Georges Francois Leclerc2 sites in 1 country86 target enrollmentNovember 27, 2024

Overview

Brief Summary

This study (phase I clinical trial and expansion cohorts) will evaluate safety and efficacy of combination of atezolizumab and tiragolumab, with concomitant or sequential SBRT for four oligometastatic cancer cohorts. This study will allow to developpe one or several randomized Phase II clinical trials for the more promising indications

Detailed Description

This study will be composed of 2 stepms. First step will be a phase I with the aim to establish the recommended safety scheme of administration (concomitant or sequential) of tiragolumab + atezolizumab + SBRT. The phase I will enrolled only patients from the cohort 1 (metastatic non-small cell lung cancer). The second step will be an expansion cohorts phase at the recommended scheme of administration. The second step will enrolled patients from 4 different cohorts (metastatic non-small cell lung cancer, metastatic bladder cancer, metastatic renal cell carcinoma, metastatic head and neck carcinoma).

Registry

euclinicaltrials.eu

Start Date

November 27, 2024

End Date

TBD

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Investigators

Sponsor

Centr Georges Francois Leclerc

Responsible Party

Principal Investigator

Pr François GHIRINGHELLI

Scientific

Centr Georges Francois Leclerc

Eligibility Criteria

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arms & Interventions

Atezolizumab + Tiragolumab + SBRT

Atezolizumab + Tiragolumab (every 21 days during 24 months or until progression) + SBRT (treatment will be delivered on 5 days). The combination of SBRT and Immunotherapies will be performed using to different schemes. For the 6 first inclusions the combination will use a sequential scheme. If the safety criteria are respected the following patients will be able to be treated by concomitant scheme.

Intervention: Atezolizumab 60 MG/1 ML Intravenous Solution [TECENTRIQ]

Atezolizumab + Tiragolumab + SBRT

Atezolizumab + Tiragolumab (every 21 days during 24 months or until progression) + SBRT (treatment will be delivered on 5 days). The combination of SBRT and Immunotherapies will be performed using to different schemes. For the 6 first inclusions the combination will use a sequential scheme. If the safety criteria are respected the following patients will be able to be treated by concomitant scheme.

Intervention: Tiragolumab

Atezolizumab + Tiragolumab + SBRT

Atezolizumab + Tiragolumab (every 21 days during 24 months or until progression) + SBRT (treatment will be delivered on 5 days). The combination of SBRT and Immunotherapies will be performed using to different schemes. For the 6 first inclusions the combination will use a sequential scheme. If the safety criteria are respected the following patients will be able to be treated by concomitant scheme.

Intervention: Stereotactic body radiation therapy (SBRT)

Outcomes

Primary Outcomes

Phase I : to evaluate safety of SBRT

Time Frame: the first 4 weeks (28 days) after the first dose of study treatement for concomitant administration (3X8 Gy of radiotherapy and 3 dosing of immunotherapies)

Using the following DLTs (DLT are defined by the following events related to study treatments (SBRT and/or tiragolumab, atezolizumab) : * grade 3 pneumopathy (except if return to grade ≤2 within 7 days) * grade 3 radiation dermatitis (except if return to grade ≤2 within 2 weeks). * grade 4 of any other toxicity (except if return to ≤ G3 within 2 weeks) * for all any grade 4 adverse event which lead to treatment discontinuation of more than 7 days

Secondary Outcomes

Expansion cohort : overall survival (OS) following SBRT, atezolizumab and tiragolumab combination(Until the patient dies)
Expansion phase : The 6-month progression free survival (PFS) rate after SBRT, atezolizumab and tiragolumab combination.(During 6 months after inclusion)
Expansion cohort : The Duration of Response (DOR) and non progression duration (NPD) following SBRT, atezolizumab and tiragolumab combination(Throughout the treatment period (24 months))
Expansion cohort : The long term safety of SBRT, atezolizumab and tiragolumab antibodies combination(Throughout the treatment period (24 months))
Expansion cohort : Overall Response rate (ORR) and Non progression rate (NPR) following SBRT, atezolizumab and tiragolumab combination(18 weeks after inclusion)
Expansion cohort : To evaluate abscopal effect(Throughout the treatment period (24 months))