Tiragolumab, Atezolizumab and Chemotherapy in Triple Negative Breast Cancer

NCT06175390 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: IC 2022-01
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Triple Negative Breast Cancer

Keywords

Triple Negative Breast Cancer; Atezolizumab; Tiragolumab; 68Ga-FAPI-46

Outcome Measures

Primary Outcomes (3)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability].

  In Safety run-in, safety and toxicity of the combination Atezolizumab + Tiragolumab + chemotherapy in cohorts A

  6 weeks for cohort A and 8 weeks for cohort B

• In cohort A, Rate of pathological complete response (pCR)

  pCR is defined as ypT0/Tis ypN0 (i.e., no invasive residual in breast or nodes; as centrally assessed at the time of definitive surgery).

  6 months

• In cohort B, Progression-free survival rate (6mPFS),

  6mPFS is defined as the proportion of patients without progression (as assessed by central review per Positron Emission Tomography Response Evaluation Criteria in Solid Tumors (PERCIST) v1.0) or death within 6 months after the date of inclusion.

  6 months

Secondary Outcomes (9)

• SAEs (serious adverse events) and AEs (adverse events)

  36 months

• In Cohort A, alternative definition of pCR rate: Residual cancer burden (RCB)

  6 months

• In Cohort A, alternative definition of pCR rate: ypT0 ypN0 (no invasive or noninvasive residual in breast or nodes

  6 months

• In Cohort A, Invasive disease-free survival (iDFS)

  3 years

• In Cohort B, Objective response rate (ORR)

  6 months

Study Arms (2)

Cohort A: early Triple Negative Breast Cancer

EXPERIMENTAL

Patients will receive neoadjuvant therapy with four cycles of 1200 mg of atezolizumab and 600 mg of Tiragolumab every 3 weeks in combination with nab-paclitaxel 100 mg/m2 on days 1, 8, and 15, every 3 weeks plus carboplatin AUC 5 on days 1 every 3 weeks then four cycles of 1200 mg of atezolizumab (Tecentriq®, Roche) and 600 mg of Tiragolumab (Roche) every 3 weeks in combination with Doxorubicin 60 mg/m2 plus Cyclophosphamide 600 mg/m2. After surgery, patients will receive adjuvant treatment with atezolizumab plus tiragolumab every 3 weeks for up to nine cycles (in patients with germline BRCA1/2 mutation eligible to adjuvant olaparib, tiragolumab and atezolizumab will not be resumed after surgery).

Radiation: 68Ga-FAPI-46 PET/CT; Biological: Tumor samples analysis; Biological: Blood samples analysis: Circulating Tumor DNA

Cohort B: metastatic Triple Negative Breast Cancer

EXPERIMENTAL

Patients will receive atezolizumab 1680 mg administered by IV infusion Q4W, plus tiragolumab 840 mg administered by IV infusion Q4W, plus nab-paclitaxel 100 mg/m2 administered by IV infusion d1, d8, d15 of every 28-day cycle. Treatments will be administered until disease progression or limiting toxicity.

Radiation: 68Ga-FAPI-46 PET/CT; Biological: Tumor samples analysis; Biological: Blood samples analysis: Circulating Tumor DNA

Interventions

68Ga-FAPI-46 PET/CT RADIATION

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.

Cohort A: early Triple Negative Breast Cancer; Cohort B: metastatic Triple Negative Breast Cancer

Tumor samples analysis BIOLOGICAL

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.

Cohort A: early Triple Negative Breast Cancer; Cohort B: metastatic Triple Negative Breast Cancer

Blood samples analysis: Circulating Tumor DNA BIOLOGICAL

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).

Cohort A: early Triple Negative Breast Cancer; Cohort B: metastatic Triple Negative Breast Cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years old
• Female
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Histological diagnosis of carcinoma of the breast, according to AJCC 8th edition that is estrogen receptor negative (ER-), progesterone receptor negative (PR-) and HER2- negative according to local testing on the most recent tumor sample examined before signing consent form to participate in the study.
• ER-negative and PR-negative are defined as having an immunohistochemistry (IHC) \< 10%
• HER2 negative is defined as per the 2018 American Society of Clinical Oncology (ASCO) - College of American Pathologists (CAP) guidelines, indeed as having an IHC of 0 or 1+ without ISH OR IHC 2+ and ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number \< 4 signals/cells OR ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number \< 4 signals/cells \[without IHC\]; Note: a IHC of 3+ is always considered HER2 positive, independently of the ISH result.
• Cohort A (early setting): patients will be enrolled regardless of their tumor PD-L1 status.
• Cohort B (metastatic setting): patients will be enrolled regardless of their tumor PD-L1 status but participants with PD-L1 negative tumor status (i.e.\<1% defined by Immunohistochemistry with Ventana SP142) will be capped at 40%. i.e.\<1% defined by immunohistochemistry with Ventana SP142) will be capped at 40%.
• Agreement to perform new study-related biopsies and blood sampling as described in the study schedule of activity.
• Tumor considered as accessible by biopsy, according to the investigator. Fine-needle aspiration, brushing, cell pellet from pleural effusion, bone metastases, and lavage samples are not acceptable. Tumor tissue from bone metastases is not acceptable.
• For female of childbearing potential (WCBP): negative serum or urinary pregnancy test within 2 weeks prior to first dose of study administration.
• Women of childbearing potential must agree to use one highly effective method of contraception during the screening period, during the course of the study and at least 12 months after the last administration of study treatment (see appendix 7) .
• Adequate bone marrow function as defined below:
• Absolute neutrophil count ≥1500/μL, i.e., 1.5x109/L Hemoglobin ≥ 9.0 g/dL Platelets ≥100000/μL, i.e., 100x109/L
• Adequate liver function as defined below:

You may not qualify if:

• Pregnant and/or lactating women.
• Contra-indications to 18F-FDG PET/CT and/or 68Ga-FAPI-46 PET/CT.
• Patients in whom tumor deposits are not detected by 18F-FDG PET/CT.
• Subject with a significant medical, neuro-psychiatric, substance abuse or surgical condition, currently uncontrolled by treatment, which, in the principal investigator's opinion, may interfere with completion of the study.
• TNM stage T4d breast cancer (inflammatory breast cancer).
• Known HIV
• Active infection including: Hepatitis B (known positive HBV surface antigen (HBsAg) result). Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible; Hepatitis C. Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, active tuberculosis, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the subject to give written informed consent.
• Concomitant use of other investigational drugs.
• Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia. Subjects with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
• Active or prior documented autoimmune disease (including inflammatory bowel disease, celiac disease, Wegener's granulomatosis) within the past 3 years.
• Note: Subjects with childhood atopy or asthma, vitiligo, alopecia, Grave's disease, Hashimoto's thyroiditis, on a stable dose of thyroid replacement hormone or psoriasis not requiring systemic treatment (within the past 2 years), and patients with controlled Type 1 diabetes mellitus on a stable insulin regimen are not excluded.
• Known history of, or any evidence of active, non-infectious pneumonitis. (Note: History of radiation pneumonitis in the radiation field \[fibrosis\] is permitted).
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
• Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary (CHO) cells or any component of the atezolizumab formulation.

Sponsors & Collaborators

• Hoffmann-La Roche: collaborator
• Institut Curie: lead

Study Sites (2)

Institut Curie

Paris, 92210, France

Location

Institut Curie

Saint-Cloud, 92210, France

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• François-Clément Bidard, PhD

  Institut Curie

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A phase II trial preceded by a safety run-in with two parallel cohorts

Study Record Dates

• First Submitted: November 27, 2023
• First Posted: December 18, 2023
• Study Start: March 27, 2024
• Primary Completion (Estimated): August 15, 2026
• Study Completion (Estimated): February 15, 2029
• Last Updated: February 6, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data requests can be submitted starting 9 months after last article publication and will be made accessible for up to 12 months.
• Access Criteria: Access to trial individual participant data can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a data sharing agreement (DSA).

Locations

FR (2)