Abstract PO5-19-08: Neoadjuvant HER2-targeted Therapy +/- Immunotherapy with Pembrolizumab (neohip): an Open Label Randomized Phase II Trial

Heather McArthur,Jorge Henrique Santos Leal，Katherine Sanchez,David Page

Cancer Research（2024）

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Abstract

Abstract Background: Immune checkpoint inhibition (ICI) is synergistic with HER2-directed therapy in pre-clinical models. Clinically, pembrolizumab (K)-mediated ICI plus HER2-directed therapy with trastuzumab (H) was safe and demonstrated modest activity in H-resistant HER2-positive (HER2+) metastatic breast cancer. Because ICI may confer more robust activity when administered earlier in the course of disease, H and K administered in the curative-intent, treatment-naive setting may allow for de-escalation of cytotoxics; confer life-long, tumor-specific immunity; and ultimately, improve cure rates. Moreover, the synergy of H and K with paclitaxel (T) may overcome the need for dual HER2-blockade with H plus pertuzumab (P). In this randomized, multicenter, phase II, open-label trial the efficacy and safety of neoadjuvant THP vs THP-K vs TH-K are explored. Methods: Patients (pts) ≥18y with previously untreated, stage II-III, HER2+ breast cancer are being randomized and stratified by clinical nodal status (positive vs. negative) and hormone receptor status (positive vs. negative). In arm A, pts receive T at 80mg/m2 weekly for 12 weeks, H at 8mg/Kg (loading dose) and then 6mg/Kg every 3 weeks x 3 doses, P at 840 mg (loading dose) and then 420mg/Kg every 3 weeks x 3 doses (THP). In arm B, pts receive THP plus K at 200mg every 3 weeks x 4 doses (THP-K). In arm C, pts receive TH-K. After enrollment of 22 pts to arm C, a prespecified interim efficacy analysis was conducted, and enrollment to this arm was subsequently terminated. Enrollment to the other arms continues with 32/58 pts enrolled to arm A and 33/58 pts enrolled to arm B as of 2/14/2023. Definitive surgery is 3-6 weeks after the last dose. After surgery, pts are treated per the treating physician’s discretion per local clinical standard. The primary end point is pathologic complete response (pCR) rate in the breast and axilla (ypT0/Tis ypN0). Secondary end points include pCR rate by ypT0ypN0 and ypT0/Tis, residual cancer burden index, event free survival, breast conserving surgery rate, safety and overall survival. Exploratory correlative studies will characterize potential immune biomarkers predictive of efficacy and/or toxicity. Funding sources: BCRF, Merck NCT03747120 Citation Format: Heather McArthur, Jorge Henrique Santos Leal, Isaac Chan, Nisha Unni, Stephen Shiao, Joshua Gruber, Samira Syed, Namrata Peswani, Navid Sadeghi, Glenda Delgado, Dawn Klemow, Reva Basho, Meredith Carter, Mai Badran, Nasir Qureshi, Jessica Curtin, Joshua Weese, Stephanie Rice, Michelle Phillips, David Chan, Hugo Hool, Dorothy Park, Mary El-Masry, Philomena McAndrew, Swati Sikaria, Laura Spring, Aditya Bardia, Mourad Tighiouart, Farnaz Dadmanesh, Armando Giuliano, Katherine Sanchez, David Page. Neoadjuvant HER2-targeted Therapy +/- Immunotherapy with Pembrolizumab (neoHIP): An Open Label Randomized Phase II Trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-19-08.

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【要点】：该研究探讨了新辅助HER2靶向治疗±帕博利珠单抗免疫疗法在HER2阳性乳腺癌患者中的疗效和安全性，旨在通过早期干预提高治愈率。

【方法】：通过开放标签、随机、多中心的II期临床试验设计，对比THP（紫杉醇+曲妥珠单抗+帕妥珠单抗）与THP-K（THP+帕博利珠单抗）及TH-K（曲妥珠单抗+帕博利珠单抗）的疗效和安全性。

【实验】：研究招募年龄≥18岁、未经治疗的II-III期HER2阳性乳腺癌患者，分为三组，分别接受THP、THP-K和TH-K治疗，目前TH-K组已停止招募，共招募了58名患者，其中32名入组THP组，33名入组THP-K组，实验以病理完全缓解（pCR）率为主要终点，实验数据截至2023年2月14日。