TerminatedPhase 2

Impact of Neoadjuvant Immunotherapy in Early Stage Breast Cancer Before Standard Therapy

Stopped: Abandon of the partner, ROCHE

France33 participantsStarted 2022-02-24

Plain-language summary

The aim of this study is to determine, using immunohistochemistry (IHC) on biopsies and surgically removed tumor if short-treatment immunotherapy with atezolizumab monotherapy or in combination with other biologic agents (ipatasertib / Bevacizumab / Trastuzumab / Pertuzumab) is associated with increased levels of activated GzmB+ CD8+ T cells from baseline to post treatment sample. Moreover, from baseline to post treatment sample, evolution of others biomarkers will be studied : GzmB/CD8, CD8/FoxP3, CD8/CD68 in IHC, cell proliferation, PD-L1, MHC-I, change in gene expression (RNA-Seq). Tjis study aim also to assess the safety and tolerability of study treatments in this population and to determine the effect of short-term immunotherapy treatment in pCR at surgery. Patients will undergo tumor biopsies at screening and 15 days after the beginning of treatment (if they start neoadjuvant chemotherapy) / at surgery, in order to evaluate in IHC evolution of activated GzmB+ CD8+ T cells and evaluate other markers It targets 2 different cohorts: newly diagnosed, non-metastatic early-stage triple-negative (TNBC) or HER2+ breast cancer. TNBC cohort is composed of 2 open-label, randomized arms, HER2+ of 2 arms. A maximum of 185 patients will be included in the trial Tumor evaluation will be performed by clinical examination and Breast echography at baseline and end of treatment visit. The safety of the product will be assessed at each cycle, through complete clinical exams, biological tests and through the collection of ongoing toxicities or adverse events.

Who can participate

Age range18 Years

SexALL

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Inclusion Criteria: * Patient should understand, sign, and date the written informed consent form prior to any protocol-specific procedures performed. Patient should be able and willing to comply with study visits and procedures as per protocol. * Female or male patients aged 18 years or older * Eastern Cooperative Group (ECOG) Performance Status 0-1 * Histologically confirmed female breast cancer with no evidence of metastatic spread * Candidate to surgery upfront or patients with an indication to standard of care neoadjuvant systemic treatment, assuming that systemic treatment starts after the completion of the pre-operative immunotherapy treatment, biopsies are undertaken before the start of the systemic treatment and the decision to administer neoadjuvant systemic treatment is made before randomization * At least 11 mm in tumor size as determined by breast ultrasound * ER, PR and HER2 will be locally assessed and defined as per the french national guidelines: * For the TNBC cohort, ER≤10%, PR≤10% and HER2 not overexpressed/amplified * For the HER2-positive cohort, presence of a HER2 overexpression and/or amplification as per ASCO/CAP guidelines * Adequate haematologic and organ function defined by the following: * ANC ≥ 1,500 cells/µl * Platelet count ≥ 100,000/µl * Haemoglobin ≥ 9.0 g/dL (90g/L) * Serum albumin ≥ 2.5 g/dL * Creatinine ≤ 1.5 x ULN * Bilirubin ≤ 1.5 x ULN, AST or ALT \< 3 x ULN, ALP \< 2.5 x ULN (patients with known Gilbert disease who h…

What they're measuring

Two-fold increase in GzmB+ CD8+ T cell levels from baseline to post-treatment window.

Timeframe: From baseline to post-treatment (14 days) window.

Trial details

NCT IDNCT05180006

SponsorGustave Roussy, Cancer Campus, Grand Paris

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2024-12-17