NCT06175390

Tiragolumab, Atezolizumab and Chemotherapy in Triple Negative Breast Cancer

Tiragolumab, Atezolizumab and Chemotherapy in Triple Negative Breast Cancer: A Phase II Trial

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 81 (actual)
• Sponsor: Institut Curie · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a phase II study, preceded by a safety run-in, with two independent cohorts (cohort A in early Triple Negative Breast Cancer (TNBC) patients and cohort B in late in metastatic TNBC patients) designed to evaluate the efficacy of atezolizumab, tiragolumab and chemotherapy.

Detailed description

In the early TNBC setting (cohort A) dedicated to patients with newly diagnosed, previously untreated, non-metastatic disease (tumor stage T1c, nodal stage N1-2, or tumor stage T2-4, nodal stage N0-2), the treatment will consist in: First part: Nab-paclitaxel administered weekly in combination with atezolizumab, tiragolumab and carboplatin, administered every 3 weeks over 12 weeks Second part: Atezolizumab, tiragolumab, doxorubicin and cyclophosphamide, administered every 3 weeks over 12 weeks Patients will undergo surgery of the primary disease 3 to 6 weeks after last neoadjuvant treatment dose, followed by 9 cycles of atezolizumab and tiragolumab administered every 3 weeks. Treatment efficacy will be assessed early on, through 18F-FDG PET/CT during the first two cycles. Patients whose tumor shows no sign of response after two cycles (i.e. no partial or complete metabolic response of the breast tumor according to 18F-FDG PET/CT by PERCIST criteria) would then be switched to standard treatment, per investigator decision. Tiragolumab 600 mg and Atezolizumab 1200 mg administered by IV infusion every 3 weeks after surgery for a total of 9 cycles. In the metastatic TNBC setting (cohort B) dedicated to patients with locally recurrent inoperable or metastatic disease eligible to first line treatment, patients will be included regardless of their PD-L1 tumor expression defined by immunohistochemistry (Ventana SP142) at baseline, but no more than 40% of PD-L1 negative (i.e \<1%) will be included. The treatment will consist in nab-paclitaxel administered at d1, d8, d15 of every 28-day cycle, combined with atezolizumab and tiragolumab administered every 3 weeks until disease progression or limiting toxicity. Treatments will be administered until disease progression or limiting toxicity. As the the combination Atezolizumab + Tiragolumab + chemotherapy has never been tested, a safety run-in phase of 10 patients is planned in each cohort to verify the tolerance of the combination

Conditions

• Triple Negative Breast Cancer

Interventions

Type	Name	Description
RADIATION	68Ga-FAPI-46 PET/CT	Cohort A: Tumor assessments by 18F-FDG PET/CT (per PERCIST v1.0) will be performed at: baseline, after the first 2 treatment cycles (between C2D15 and C3D1), and before surgery (after the last administration of neoadjuvant chemotherapy) Tumor assessment by 68Ga-FAPI-46 PET/CT will be performed at: baseline and before surgery (after the last administration of neoadjuvant chemotherapy). Cohort B: Tumor assessments by 18F-FDG PET/CT per PERCIST v1.0 will be performed at baseline, every 8 weeks (+/- 1 week) for the first 24 weeks, and every 12 weeks (+/- 1 week) thereafter until disease progression or treatment discontinuation, whichever is later. Tumor assessments by 68Ga-FAPI-46 PET/CT will be performed at baseline and after the first 2 treatment cycles and will be synchronized with 18F-FDG PET/CT.
BIOLOGICAL	Tumor samples analysis	Patients will undergo a mandatory biopsy of the primary tumor at baseline, after the first 2 treatment cycles and during the surgery. A lymph node biopsy will be performed at baseline if feasible in cohort A, and and in case of disease progression for cohort B (if clinically feasible). In addition to the usual morphological and immunohistochemical (ER, PR, HER2+, CPS score, PD-L1 status with SP142 …) analyses in the cohort A and cohort B , exploratory analyses will be performed.
BIOLOGICAL	Blood samples analysis: Circulating Tumor DNA	Blood samples will be collected at baseline. In addition for cohort A at cycles 2 and 3, within 21 days before surgery, 10 to 21 days after surgery and at cycle 8 after surgery. In addition for cohort B after the first 2 treatment cycles and in case of disease progression (if clinically feasible).

Timeline

• Start date: 2024-03-27
• Primary completion: 2026-08-15
• Completion: 2029-02-15
• First posted: 2023-12-18
• Last updated: 2026-02-06

Locations

2 sites across 1 country: France