Table 2.

Ongoing phase III clinical trials with pembrolizumab and atezolizumab in TNBC (August 2020) [20]

Trial identifier	Status	Setting	Target group	Arms/treatment	POM
NCT03036488 KEYNOTE-522	A N/R	Neoadjuvant, adjuvant	Locally advanced TNBC	1. PXL + CBDCA + placebo → AC/EC + placebo → surgery → placebo 2. PXL + CBDCA + pembrolizumab → AC/EC + pembrolizumab → surgery → pembrolizumab (Q3W)	pCR rate (ypT0/Tis ypN0)
			Treatment-naïve locally advanced non-metastatic (M0) TNBC: T1c, N1-N2 T2, N0-N2 T3, N0-N2 T4a-d, N0-N2
					EFS
NCT02954874	R	Adjuvant	TNBC or ER-, PgR- weakly positive and/or HER2-equivocal status and must not have received and not be planning to receive adjuvant anti-HER2 or ETs after completion of neoadjuvant chemotherapy	1. Observation (± Rth) 2. Pembrolizumab (every 42 days for 52 weeks) ± Rth	IDFS
			HER2- and HER2-equivocal cases as per ASCO CAP guidelines that do not receive HER2-targeted therapy
			Weakly ER or PgR positive disease (ER and/or PgR ≤ 5% by IHC) are eligible if the patient is not eligible for adjuvant ET		Severity of fatigue
			Residual disease must be ≥ 1 cm in greatest dimension, and/or ypN1mi, ypN1, ypN2, ypN3		Physical function
NCT02819518 KEYNOTE-355	A N/R	Recurrence, Metastatic	Treatment-naïve: locally recurrent inoperable breast cancer which cannot be treated with curative intent	Part 1: 1. Pembrolizumab (200 mg/Q3W) + nab-PXL 2. Pembrolizumab (200 mg/Q3W) + PXL 3. Pembrolizumab (200 mg/Q3W) + GEM/CBDCA Part 2: 1. Pembrolizumab (200 mg/Q3W) + chemotherapy 2. Placebo + chemotherapy	Part 1: percentage of participants who experience an AE—all
					Percentage of participants who discontinue study drug due to an AE—all
					Part 2: PFS and OS—all
			MBC		PFS and OS in those with PD-L1–positive CPS ≥ 1 tumours, and with CPS ≥ 10 tumours
NCT04191135 KEYLYNK-009	R	Recurrence, metastatic	Treatment-naïve: locally recurrent inoperable TNBC that cannot be treated with curative intent	1. CBDCA + GEM +  pembrolizumab → CBDCA + GEM + pembrolizumab (200 mg/Q3W) 2. CBDCA + GEM + pembrolizumab →  pembrolizumab (200 mg/Q3W) + olaparib	PFS
			MBC		OS
NCT02620280 NeoTRIPaPDL1	A N/R	Neoadjuvant adjuvant	Early high-risk and locally advanced or inflammatory breast cancers	1. CBDCA + nab-PXL + atezolizumab → surgery → AC or EC or FEC 2. CBDCA + nab-PXL → surgery → AC or EC or FEC	EFS
NCT03498716 IMpassion030	R	Neoadjuvant adjuvant	Operable stage II-III	1. Atezolizumab (840 mg/Q2W) + PXL → atezolizumab + ddAC/ddEC → surgery  → atezolizumab (1200 mg/Q3W to complete 1 year of treatment from the first dose) 2. PXL → ddAC/ddEC → surgery	IDFS
NCT03197935 IMpassion031	A N/R	Neoadjuvant adjuvant	cT2-cT4, cN0-cN3, cM0	1. Atezolizumab (840 mg/Q2W) + nab-PXL  → atezolizumab (840 mg/Q2W) + AC → surgery → atezolizumab (1200 mg/Q3W, 11 doses) 2. Placebo + nab-PXL → placebo + AC → surgery	Percentage of participants with pCR
					Percentage of participants with pCR in subpopulation with PD-L1–positive tumour status
NCT03281954	R	Neoadjuvant, adjuvant	T2 or T3, N0	1. PXL + CBDCA + placebo → AC/EC + placebo → surgery → placebo 2. PXL + CBDCA + atezolizumab → AC/EC + atezolizumab → surgery → atezolizumab (1200 mg/Q3W)	pCR in the breast and lymph nodes (ypT0/Tis ypN0)
			cN1 (cytologically or histologically positive) or cN2-N3 (with or without a biopsy), then can be clinically T1c, T2, or T3		EFS
NCT03125902 IMpassion131	A N/R	Locally advanced, metastatic	Treatment-naïve: locally advanced	1. Atezolizumab (840 mg/Q2W) + PXL 2. Placebo + PXL	PFS in the subpopulation with PD-L1(+) tumour status
			MBC not amenable to surgical therapy		PFS in the intent-to-treat population
NCT03371017 IMpassion132	R	Recurrence, locally advanced, metastatic	Treatment-naïve: locally recurrent, inoperable	1. Atezolizumab (1200 mg/Q3W) + chemotherapy (GEM + CBDCA or capecitabine) 2. Placebo + chemotherapy (GEM + CBDCA or capecitabine)	OS in population with PD-L1(+) tumour status
			Locally advanced		OS in modified intent-to-treat popluation
			MBC
NCT04177108	R	Locally advanced unresectable, metastatic	Treatment-naïve: locally advanced unresectable	PD-L1(-): 1. PXL + atezolizumab  + ipatasertib 2. PXL + placebo + ipatasertib 3. PXL + placebo + placebo PD-L1(+): 1. PXL + atezolizumab + ipatasertib 2. PXL + atezolizumab + placebo	PFS
			MBC		OS

TNBC triple-negative breast cancer, POM primary outcome measures, A N/R Active not recruiting, PXL paclitaxel, CBDCA carboplatin, AC/EC doxorubicin plus cyclophosphamide/epirubicin plus cyclophosphamide, Q3W every 3 weeks, pCR pathological complete reponse, EFS event-free survival, R recruiting, ER estrogen receptor, PgR progesterone receptor, HER2 human epidermal growth factor receptor 2, ET endocrine therapy, ASCO CAP American Society of Clinical Oncology College of American Pathologists, IHC immunohistochemistry, Rth radiotherapy, IDFS invasive disease-free survival, MBC metastatic breast cancer, GEM gemcitabine, AE adverse event, PFS progression-free survival, OS overall survival, PD-L1 programmed cell death ligand 1, CPS combined positive score, FEC fluorouracil, epirubicin and cyclophosphamide, Q2W every 2 weeks, dd dose-dense