TIP in Patients Affected by Metastatic TNBC

Metastatic Triple-negative Breast Cancer Clinical Trial

— TIP  

Official title:

Evaluation of a Tissue Immune Profile (TIP) in Patients Affected by Metastatic TNBC Treated With Upfront Atezolizumab Plus Nab-paclitaxel (TIP)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05831553
• Other study ID #: FMP-2020-01-TIP
• Status: Recruiting
• Start date: September 16, 2022
• Est. completion date: September 16, 2025

Study information

• Verified date: May 2023
• Source: Fondazione per la Medicina Personalizzata
• Contact: Paolo Marchetti
• Phone: +393356105946
• Email: coordinamentofmp[@]gmail.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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. 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. 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. 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.

We defined a tissue immune profile positive (TIP+) as the simultaneous presence of TILs≥50%, CD73≤40% and PD-L1≥1%. Any other combination was defined as TIP negative (TIP-) In conclusion, we will evaluate the association between TIP and clinical outcomes (ORR, PFS, OS).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: September 16, 2025
• Est. primary completion date: September 16, 2025
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Metastatic Triple-negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Diagnostic Test:
• Tissue Immune Profile
Tissue samples of the patients will be analized for the presence of TILs, CD73 and PDL1 (>=1%)

Locations

Country	Name	City	State
Italy	IRCCS Istituto Europeo di Oncologia IEO	Milano	MI
Italy	Istituto Nazionale per lo Studio e la Cura dei Tumori - Fondazione S. Pascale	Napoli
Italy	Ospedale Santo Stefano	Prato	FI
Italy	Azienda Ospedaliero Universitaria Policlinico Umberto I	Roma	RM
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma	RM
Italy	ospedale Belcolle	Viterbo	VT

Sponsors (2)

Lead Sponsor	Collaborator
Fondazione per la Medicina Personalizzata	University of Roma La Sapienza

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival	After 12 months from patient enrollment, the presence of disease progression will be assessed	12 months
Secondary	months of Overall Response Rate	To evaluate the association between immune profile (TIP) and Objective Response Rate	through study completion, an average of 1 year
Secondary	months of Overall Survival	To evaluate the association between immune profile (TIP) and Overall Survival	through study completion, an average of 1 year