Abstract P2-09-07: Preoperative pembrolizumab (Pembro) with radiation therapy (RT) in patients with operable triple-negative breast cancer (TNBC)
Authors: McArthur HL , Basho R , Shiao SL , Park D , Mita M , Chung A , Arnold B , Martin C , Dang C , Karlan S , Knott S , Giuliano A , Ho A 
Published: May 2019

Abstract
Background: Radiation therapy (RT) induces immune-mediated cell death and could generate a rich supply of tumor antigens if administered in the pre-operative, curative-intent setting. The addition of PD-1 mediated checkpoint blockade to pre-operative RT could thus, generate robust anti-tumor immune responses, induce long-term tumor-specific memory, and ultimately, improve cure rates. This study aims to establish the safety of pre-operative pembrolizumab (pembro)-mediated immune modulation with a RT “boost” equivalent in patients with operable triple negative breast cancer (TNBC) for whom lumpectomy and adjuvant RT are planned (NCT03366844). Serial research biopsies permit interrogation of conventional biomarkers including tumor infiltrating lymphocytes (TILs) and novel immune correlates as potential predictors of response to pembro alone versus pembro with RT.
Methods: Ten women with operable, primary TNBC &gt;2cm for whom breast-conserving therapy is planned are being enrolled in this single-institution pilot study. Study treatment consists of 1 cycle of pre-operative pembro (200 mg IV) alone, followed 3 weeks later by a RT boost (24 Gy/3 fractions) to the primary breast tumor concurrently with pembro (+/- 5 days). Curative-intent, standard-of-care, neoadjuvant chemotherapy (NAC) or breast-conserving surgery is then undertaken within 8 weeks of study enrollment (i.e. within 5 weeks of pembro #2). Adjuvant RT is administered per standard-of-care after surgery, but without a boost dose. Research blood and fresh tumor biopsies are obtained at baseline and after cycles 1 and 2 of pembro. Co-primary endpoints are: 1) safety/tolerability, as defined by the number of patients who do not necessitate a delay in standard-of-care chemotherapy or surgery and 2) change in TIL score. Secondary endpoints include safety/toxicity up to 19 weeks after study enrollment, pCR rates and disease-free survival. Correlative analysis will include single-cell RNA sequencing of the tumor immune infiltrate and multispectral immunohistochemistry
Results: Seven patients enrolled between 12/19/17 and 7/1/18. As of 7/1/18, 5 patients have completed the experimental pembro/RT phase of the trial and are currently completing standard-of-care NAC; 1 patient is currently being treated in the experimental pembro/RT phase; and 1 patient with a cT2N0 tumor at baseline achieved a pathologic complete response (pCR, ypT0/Tis ypN0) after completing the experimental pembro/RT phase followed by anthracycline- and taxane-based NAC. No grade 3 or 4 toxicities have been observed during pembro/RT in the 6 patients completing the experimental phase to date. Three additional patients will be enrolled
Conclusions: This is the first trial of curative-intent, pre-operative checkpoint blockade with RT in breast cancer and the strategy appears to be well tolerated to date. At the time of presentation, safety, change in TIL score, and pCR rates for all patients completing the experimental and NAC phases of the study will be reported.
Citation Format: McArthur HL, Basho R, Shiao SL, Park D, Mita M, Chung A, Arnold B, Martin C, Dang C, Karlan S, Knott S, Giuliano A, Ho A. Preoperative pembrolizumab (Pembro) with radiation therapy (RT) in patients with operable triple-negative breast cancer (TNBC) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-09-07.