TIP in Patients Affected by Metastatic TNBC (TIP)

May 3, 2023 updated by: Fondazione per la Medicina Personalizzata

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

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Anticipated)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
      • Napoli, Italy, 80131
        • Recruiting
        • Istituto Nazionale per lo Studio e la Cura dei Tumori - Fondazione S. Pascale
        • Contact:
          • Roberta Caputo, dr
    • FI
      • Prato, FI, Italy, 59100
        • Recruiting
        • Ospedale Santo Stefano
        • Contact:
          • Emanuela Risi, dr
    • MI
      • Milano, MI, Italy, 20141
        • Suspended
        • IRCCS Istituto Europeo di Oncologia IEO
    • RM
      • Roma, RM, Italy, 00168
        • Recruiting
        • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
        • Contact:
          • Ida Paris
      • Roma, RM, Italy, 00198
        • Recruiting
        • Azienda Ospedaliero Universitaria Policlinico Umberto I
        • Contact:
          • Andrea Botticelli
    • VT
      • Viterbo, VT, Italy, 01100
        • Not yet recruiting
        • Ospedale Belcolle
        • Contact:
          • Agnese Fabbri, dr

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

N/A

Sampling Method

Probability Sample

Study Population

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

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival
Time Frame: 12 months
After 12 months from patient enrollment, the presence of disease progression will be assessed
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
months of Overall Response Rate
Time Frame: through study completion, an average of 1 year
To evaluate the association between immune profile (TIP) and Objective Response Rate
through study completion, an average of 1 year
months of Overall Survival
Time Frame: through study completion, an average of 1 year
To evaluate the association between immune profile (TIP) and Overall Survival
through study completion, an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione per la Medicina Personalizzata

Collaborators

University of Roma La Sapienza

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 16, 2022

Primary Completion (Anticipated)

September 16, 2025

Study Completion (Anticipated)

September 16, 2025

Study Registration Dates

First Submitted

March 20, 2023

First Submitted That Met QC Criteria

April 14, 2023

First Posted (Actual)

April 26, 2023

Study Record Updates

Last Update Posted (Estimate)

May 4, 2023

Last Update Submitted That Met QC Criteria

May 3, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FMP-2020-01-TIP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Metastatic Triple-negative Breast Cancer

Clinical Trials on Tissue Immune Profile

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Congo, DR of

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe