TIP in Patients Affected by Metastatic TNBC

NCT05831553 | Unknown

• 1 other identifier: FMP-2020-01-TIP
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 6

Brief Summary

Triple-negative breast cancer (TNBC) is defined by the absence of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) expression on cancer cells. TNBCs accounts for 15-20% of all breast cancers (BC).1 It is characterized by a worse prognosis, increased risk of metastasis to vital organs and a relative lack of therapeutic target if compared to other BC subtypes.2 Therefore, the identification of new molecular targets and therapeutic strategies is a critical need in both early and metastatic setting. TNBC appears to be more immunogenic compared to other BC6. Immunotherapy has recently changed the landscape of therapeutic options in TNBC. Recent clinical trials have shown a significant clinical benefit in patients with metastatic TNBC treated with a combination of chemotherapy and anti PD-1 agents.11-12-13-14-15 In particular, results from IMPASSION 130 trial showed a significant benefit in both progression free survival (PFS) and overall survival (OS) in PD-L1 positive (PD-L1+) patients treated with a combination of atezolizumab and nab-paclitaxel.20 However, about 70% of PD-L1+ patients has experienced a disease progression after one year and about 50% was alive at 2 year. Moreover, no difference in survival endpoint has been seen in PD-L1 negative (PD-L1-) population, with an increase of toxicity and costs related to the addition of a checkpoint-inhibitor. Therefore, the identification of novel biomarkers in addition to PD-L1 and the combination of several biomarkers in a profile with higher predictive capacity is considered an area of urgent clinical need. Some immune-related features that can be identified in tumor microenvironment have been demonstrated to be independent prognostic and predictive factors: TILs, PD-L1, CD73.

1. 1.Tumour-infiltrating lymphocytes (TILs) control the clinical progression of various types of cancer7. Breast cancer with higher levels of infiltrating CD8+ cytotoxic T cells have been associated with better patient survival8. Moreover, high levels of stromal CD8+ TILs (sTILs) correlate with higher probability of pCR9. Not only quantitative, but also qualitative analysis of TILs is a promising research area. Some studies suggest that different subtypes of TILs may have an opposite role in tumor microenvironment allowing the induction of both immune activating (es. CD8+) or immune suppressive (es FOXP3+) environment8-9-10.
2. 2.The interaction between programmed cell death protein 1 (PD-1) and its ligand (PD-L1) represents one of the principal mechanisms of immune escape and a therapeutic target for several malignancies13-14. PD-1/PD-L1 interaction attenuates lymphocyte activation and promotes T-regulatory cell development and function, allowing to terminate the immune response15. In breast cancer the prognostic role of PD-1/PD-L1 axis is still uncertain with limited and contrasting data. PD-L1 positivity (≥1%) on immune cells (IC) is the clinical most used threshold, according to the results of IMPASSION 130 trial.18-24
3. 3.Recently, CD73 has been identified as a possible further molecular immunosuppressive target in triple negative breast cancer28. CD73 is expressed on the surface of tumoral cells, stromal cells and immunological cells. By increasing extracellular levels of adenosine monophosphate , CD73 suppresses immune responses. CD73 has been found to be overexpressed in several types of human cancers, and it has been associated with a poor prognosis29-30-31. Particularly Loi et al demonstrated that high CD73 expression is associated with poor prognosis in TNBC and to a low rate of pathological complete response32.

Conditions

Metastatic Triple-negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  After 12 months from patient enrollment, the presence of disease progression will be assessed

  12 months

Secondary Outcomes (2)

• months of Overall Response Rate

  through study completion, an average of 1 year

• months of Overall Survival

  through study completion, an average of 1 year

Interventions

Tissue Immune Profile DIAGNOSTIC_TEST

Tissue samples of the patients will be analized for the presence of TILs, CD73 and PDL1 (\>=1%)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Female patients affected by metastatic TNBC (PDL1\>1%) treated with upfront atezolizumab plus nab-paclitaxel

You may qualify if:

• Patients able and willing to provide a written informed consent to participate to the study;
• Histological confirmed diagnosis of PD-L1 positive TNBC (\> 1%)
• Confirmed radiological or histological diagnosis of metastatic TNBC
• Availability of tumor specimen in order to perform the requested analysis
• Patients eligible for or treated with atezolizumab plus nab-paclitaxel first line as requested for clinical practice
• Availability of complete clinical data on duration, efficacy and safety of the treatment

You may not qualify if:

• Sample not sufficient to perform the requested tissue analysis
• Patients unable to provide informed consent or with possible poor compliance with protocol procedures
• Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule;
• Patients treated with the following drugs, because of the risk of immunosuppression: Chronic or high-dose oral corticosteroid therapy, TNF-inhibitors and Anti-T cell antibodies
• Patients participating in other clinical studies.

Sponsors & Collaborators

• Fondazione per la Medicina Personalizzata: lead
• University of Roma La Sapienza: collaborator

Study Sites (6)

Ospedale Santo Stefano

Prato, FI, 59100, Italy

RECRUITING

IRCCS Istituto Europeo di Oncologia IEO

Milan, MI, 20141, Italy

SUSPENDED

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, RM, 00168, Italy

RECRUITING

Azienda Ospedaliero Universitaria Policlinico Umberto I

Roma, RM, 00198, Italy

RECRUITING

ospedale Belcolle

Viterbo, VT, 01100, Italy

NOT YET RECRUITING

Istituto Nazionale per lo Studio e la Cura dei Tumori - Fondazione S. Pascale

Napoli, 80131, Italy

RECRUITING

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

Central Study Contacts

Paolo Marchetti

CONTACT

+393356105946; coordinamentofmp@gmail.com

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: OTHER
• Target Duration: 24 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2023
• First Posted: April 26, 2023
• Study Start: September 16, 2022
• Primary Completion: September 16, 2025
• Study Completion: September 16, 2025
• Last Updated: May 6, 2023

Record last verified: 2023-05

Locations

IT (6)