Table 2.

Ongoing phase II/III clinical trials investigating TILs as a biomarker in invasive breast cancer.

Trial identifier and phase	Sample size	Setting	Purpose	Estimated primary completion date	Sponsor
NCT04188119 (IMpALA) Phase II	42	Triple-negative breast cancer (TNBC)	Assessment of post treatment tumor-infiltrating lymphocytes (TILs) by immunohistochemistry (as secondary outcome measure)	June 2021	The Christie NHS Foundation Trust
NCT03863301 (ABLATIVE-2) Phase II	70	Non-lobular invasive BC	Assessment TILs at baseline on biopsies and after surgery and their correlation with the pathological response (as a secondary outcome measure)	November 2022	UMC Utrecht, Netherland
NCT03820141 (DTP Trial) Phase II	39	HER2-amplified BC	Correlation of pathological complete response rate in BC patients with TILs (as secondary outcome measure)	March 2023	AstraZeneca
NCT03359954 Phase II	20	HR+/ HER2- BC	Evaluation of changes in TILs as a continuous variable before and after preoperative radiotherapy (RT) (as primary objective)	October 2019	M.D. Anderson Cancer Center
NCT03971045 (PERICLES) Phase II	46	Locally advanced “chest wall” BC	Positive PD-L1 (≥1%) and/or TILs (≥1%) as biomarkers for patient selection in locally advanced BC previously treated with chemotherapy or radiation therapy	July 2021	European Institute of Oncology
NCT02883062 Phase II	72	Newly diagnosed, stage II-III TNBC	Comparison of TILs percentage, PD-L1 and neoantigen load at baseline before and after therapy in patients receiving neoadjuvant chemotherapy (NACT) alone and those treated with NACT and atezolizumab in a randomized fashion	July 2020	National Cancer Institute (NCI)
NCT03366844 PhaseI/II	60	Invasive BC	TILs score changes (by Salgado et al. criteria)	January 2021	Cedars-Sinai Medical Center
NCT02435680 Phase II	50	Advanced TNBC with high tumor-associated macrophages (TAMs)	Assessment of TILs and TAMs content in pre- and post-dose tumor biopsies (as secondary outcome measure)	December 2019	Novartis Pharmaceuticals
NCT03894007 (PREDIX II HER2) Phase II	190	HER2-amplified early BC	TILs and gut microbiota as predictors of treatment response in patients receiving atezolizumab in a randomized fashion	December 2024	Karolinska University Hospital, Sweden
NCT03004183 (STOMP) Phase II	57	Metastatic TNBC	Measurement of the changes of TILs in tumor biopsy tissues as a biomarker of response to ADV/HSV-tk + valacyclovir therapy in combination with stereotactic body radiation therapy followed by immune-checkpoint blockade	May 2022	Merck Sharp & Dohme Corp.
NCT03979508 (BEAUTY Study) Phase II	100	Surgically resectable and chemotherapy-resistant TNBC	Quantification of TILs in TNBC patients treated with abemaciclib	July 2022	Mayo Clinic in collaboration with NCI
NCT02003209 Phase III	312	Locally advanced BC	Quantification of TILs in BC patients treated with neoadjuvant chemotherapy, trastuzumab, and pertuzumab with or without estrogen deprivation	August 2021	NCI
NCT02990845 (PEER) Phase I/II	25	Premenopausal HR+/ HER2- locally advanced or metastatic BC	Study of potentially predictive biomarkers of the efficacy of the combination of pembrolizumab and exemestane/leuprolide including TILs, PD-L1, circulating tumor cells, and mutational load	December 2019	National Taiwan University Hospital in collaboration with Merck Sharp & Dohme Corp.
NCT03125928 Phase II	50	Metastatic HER2-positive BC	Investigation of predictive biomarkers of response (PD-L1 and TILs) to immune-checkpoint blockade (as secondary outcome measure)	December 2020	Fox Chase Cancer Center in collaboration with Genentech, Inc.
NCT02971761 Phase II	29	Androgen receptor-positive metastatic TNBC	Evaluation of pre-treatment PD-L1 and TILs as predictive biomarkers of pembrolizumab and enobosarm	November 2020	City of Hope Medical Center in collaboration with NCI
NCT02849496	72	Locally advanced or metastatic non-HER2-positive BC	Measurement of TILs level changes in patients treated with olaparib with or without atezolizumab	August 2020	NCI
NCT02536794 Phase II	30	Metastatic HER2-negative BC	Evaluation of tissue-based immunohistochemical expression TILs, PD-L1, and other immune-related candidate biomarkers as predictors of response to MEDI4736 in combination with tremelimumab (as secondary outcome measure)	September 2019	Northwestern University in collaboration with MedImmune LLC Avon Breast Cancer Foundation and NCI
NCT03289819 Phase II	50	Early TNBC	Assessment of stromal and intratumoral TILs collected at baseline, 12 weeks after treatment initiation, and at the surgery	November 2019	Institute for Women’s Health in collaboration with Merck Sharp & Dohme Corp. And Celgene Corporation
NCT03740893 (PHOENIX) Phase II	81	NACT resistant and residual TNBC	Study of frequency and function of subsets of TILs in patients treated with DNA damage response inhibition and/or immune-checkpoint blockade (as secondary outcome measure)	May 2021	Institute of Cancer Research, the United Kingdom in collaboration with AstraZeneca

ADV/HSV-tk adenovirus-mediated herpes simplex virus thymidine kinase, BC breast cancer, DNA deoxyribonucleic acid, HER2 human epidermal growth factor receptor, HR hormone receptor, NACT neoadjuvant chemotherapy, PD-L1 programmed death-ligand 1, RT radiotherapy, TAMs tumor-associated macrophages, TILs tumor-infiltrating lymphocytes, TNBC triple-negative breast cancer. Data from ClinicalTrials.gov (accessed 15 December 2019).