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. 2024 Oct 1;9(10):103713. doi: 10.1016/j.esmoop.2024.103713

Table 2.

Ongoing WOO trials assessing ICIs or novel immunotherapy agents in TNBC patients

Trial name Phase and NCT Patient population Number of patients Drug/s assessed in the WOO Treatment after WOO Endpoints Estimated completion date
AWARE-1
Phase I
NCT04102618 		All breast cancer subtypes 26
  • -

    Cohort 1 (ER+ HER2−): pelareorep + letrozole

  • -

    Cohort 2 (ER+HER2−): pelareorep + letrozole + atezolizumab

  • -

    Cohort 3 (TNBC): pelareorep + atezolizumab

  • -

    Cohort 4 (ER+ HER2+): pelareorep + trastuzumab + atezolizumab

  • -

    Cohort 5 (ER− HER2+): pelareorep + trastuzumab + atezolizumab

  • -

    Cohort 6 (HER2+ irrespective of ER status): pelareorep + trastuzumab

 Surgery Primary:
  • 1)

    Increase of CelTIL score in all cohorts [time frame: baseline (pre-treatment), day 3, and at surgery (day ∼21)]

Key secondary:
  • 1)

    Increase of CelTIL score in ER+ HER2− and HER2+ [time frame: baseline (pre-treatment), day 3, and at surgery (day ∼21)]

  • 2)

    Gene expression changes between pre- and post-treatment samples [time frame: throughout]

 April 2022
(Early termination when the study met the primary objectives with cohorts 1-4. Only results from cohorts 1 and 2 have been published)
P-RAD
Phase II
NCT04443348 		TNBC and ER+ HER2− 120
  • -

    Arm A: no RT + up to 4 × pembro Q3w

  • -

    Arm B: low-dose RT + up to 4 × pembro Q3w

  • -

    Arm C: high-dose RT + up to 4 × pembro Q3w

 Standard NACT (8 cycles) + up to 4× pembro Q3w (cycles 1-4) followed by surgery. Up to 4× pembro Q3w adjuvant optional Primary:
  • 1)

    TILs, CD3+/CD8+ T-cell Breast Immunoscore by immunofluorescence [time frame: 14-21 days after 1st pembro dose]

  • 2)

    Pathological response in the lymph nodes [time frame: 7 months]


Key secondary:
  • 1)

    Residual cancer burden score [time frame: 24 weeks]

  • 2)

    pCR [time frame: 24 weeks]

  • 3)

    Change of TILs and PD-L1 [time frame: 24 weeks]

  • 4)

    Invasive disease-free survival [time frame: up to 31 months]

  • 5)

    Event-free survival [time frame: up to 31 months]

 December 2023
BreastVAX
Phase I-II
NCT04454528 		TNBC and ER+ HER2− 27
  • -

    Arm 1: radiotherapy on day-14 followed by pembro on day-7

  • -

    Arm 2: pembro on day-14 followed by radiotherapy on day-7

  • -

    Arm 3: pembro on day-14

  • -

    Arm 4: no treatment (control arm)

 Surgery Primary:
  • 1)

    Tolerability of pembro combined with radiation and no excessive delay in surgery [time frame: 2 years]

  • 2)

    Assess clinical response to treatment based on imaging and histology [time frame: 2 years]

Secondary:
  • 1)

    Changes in the Ki67+ CD8 T cells post treatment in the peripheral blood and in TILs [time frame: 2 years]

 August 2024
Pembro/IORT
Phase I
NCT02977468 		TNBC 15 Pembro at day 1 on 2 cycle + IORT on the surgery day Surgery Primary:
  • 1)

    Increase of TILs [time frame: 3 months]

 December 2024
BIS-program
Phase II
NCT05180006 		TNBC and HER2+ 210 Cohort 1 (TNBC):
  • -

    Arm 1A: no treatment

  • -

    Arm 1B: atezolizumab on day −15

  • -

    Arm 1C: atezolizumab on day −15 + ipatasertib daily for 2 weeks starting together

  • -

    Arm 1D: atezolizumab + bevacizumab on day −15

Cohort 2 (HER2+):
  • -

    Arm 2A: no treatment

  • -

    Arm 2B: atezolizumab + trastuzumab + pertuzumab on day −15

 Surgery or standard neoadjuvant treatment follow by surgery Primary:
  • 1)

    Twofold increase in GzmB+ CD8+ T cell by immunohistochemistry [time frame: 2 weeks]


Key secondary:
  • 1)

    Clinical response [time frame: 2 weeks]

  • 2)

    pCR rate [time frame: 2 weeks]

  • 3)

    Changes in CD8+, PD-L1, Ki67 and immune infiltrates [time frame: 2 weeks]

 February 2025
IMpALA
Phase II
NCT04188119 		TNBC 42
  • -

    Arm A: lansoprazole daily on day 1 + on dose of avelumab after certain time (not specified)

  • -

    Arm B: lansoprazole and aspirin daily on day 1 + one dose of avelumab after certain time (not specified)

 Surgery or standard neoadjuvant treatment followed by surgery Primary:
  • 1)

    Mean combined gene expression of COX-2 tumor-promoting genes [time frame: 7 weeks]


Key secondary:
  • 1)

    Post-treatment TILs [time frame: 7 weeks]

  • 2)

    Mean combined gene expression of the cancer-inhibitory genes in the COX-2 inflammatory signature [time frame: 7 weeks]

 May 2025
PHOENIX DDR/anti-PD-L1
Phase II
NCT03740893 		TNBC with DDR 81 PART 1: after NACT, preoperative WOO of 2 weeks
  • -

    Cohort A: standard treatment

  • -

    Cohort B: ceralasertib twice daily for days 1-14

  • -

    Cohort C: olaparib twice daily for days 1-14

  • -

    Cohort D: durvalumab on day 1

PART 2: post-operative treatment for 12 months of the same cohorts B-D.		 Surgery only for PART 1
No following treatment in PART 2		 Primary:
  • 1)
    Cohort B and C co-primary endpoints:
    • -
      Change in mean Ki67 after WOO (≥ 33% decrease) [time frame: 2 weeks]
    • -
      Changes in proliferation 11-gene signature after WOO (≥1.5-fold drop) [time frame: 2 weeks]
  • 2)
    Cohort D co-primary endpoints:
    • -
      Change in CD8+ TILs after WOO (≥twofold increase) [time frame: 2 weeks]
    • -
      Change in IFN-γ+ 4-gene signature after WOO (≥twofold increase) [time frame: 2 weeks]

Key secondary:
  • 1)

    Changes in phosphorylation of ATR and downstream effectors [time frame: 2 weeks]

  • 2)

    Changes in biomarkers of DDR and adaptive and innate immune response [time frame: 2 weeks]

  • 3)

    Changes in the levels of Th1/IFN-γ response [time frame: 2 weeks]

  • 4)

    Immune cell population sub-set characterization (T and B cell receptor) [time frame: 2 weeks]

 December 2025
BRE-03
Phase I
NCT04427293 		TNBC 12 Lenvatinib daily for 7 days + pembro on day 1 NACT (+/− pembro) followed by surgery, or surgery followed by adjuvant therapy if applicable Primary:
  • 1)

    Infiltration of CD8+ TILs (CD45RA-/CD8+/FoxP3-) in primary tumors [time frame: 2 years]


Secondary:
  • 1)

    pCR rate and Ki67 changes [time frame: at surgery]

  • 2)

    Tolerability assessed by failure to complete NACT [time frame: 30 days after treatment]

 July 2026
Nivolumab - Ipilimumab - Cryoablation
Phase II
NCT03546686 		TNBC 80 Ipilimumab + nivolumab followed by cryoablation Surgery followed by 3× adjuvant nivolumab Q2w Primary:
  • 1)

    Event-free survival [time frame: 36 months]

Secondary:
  • 1)

    Invasive disease-free survival [time frame: 36 months]

  • 2)

    Distant disease-free survival [time frame: 36 months]

  • 3)

    Overall survival [time frame: 36 months]

  • 4)

    overall safety [time frame: 36 months]

 June 2026
POP-Durva
Phase II
NCT05215106 		TNBC (cT1N0) 200 Durvalumab ×2 Surgery or standard neoadjuvant treatment followed by surgery Primary:
  • 1)

    pCR [time frame: day 29 (surgery upfront) or day 22 (patients receiving neoadjuvant treatment]

Key secondary:
  • 1)

    Evaluation of objective response rate [time frame: after 2 administrations of durvalumab]

 June 2026

ATR, ataxia telangiectasia mutated and rad3-related; CelTIL, tumor-infiltrating lymphocytes that takes into account the tumor and lymphocyte cellularity; DDR, DNA damage response; ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; IFN-γ, interferon-gamma; IORT, intraoperative radiation therapy; NACT, neoadjuvant chemotherapy; NCT, clinicaltrials.gov number; pCR, pathological complete response; pembro, pembrolizumab; RT, radiotherapy; SBRT, stereotactic body radiation therapy; TILs, tumor-infiltrating lymphocytes; TNBC, triple-negative breast cancer; WOO, window of opportunity.