Clinical trial NCT06797635: Study of Patritumab Deruxtecan Plus Pembrolizumab With Other Anticancer Agents in Participants With High-Risk Early-Stage Triple-Negative or Hormone Receptor-Low Positive/HER-2 Negative Breast Cancer (MK-1022-010, HERTHENA-Breast-03)
Official title: An Open-label Randomized Phase 2 Study to Evaluate Safety and Efficacy of Patritumab Deruxtecan Plus Pembrolizumab Administered Either Before or After Carboplatin/Paclitaxel Plus Pembrolizumab Compared With Pembrolizumab in Combination With Chemotherapy Followed by Surgery and Adjuvant Pembrolizumab for High-Risk Early-Stage Triple-Negative or Hormone Receptor-Low Positive/Human Epidermal Growth Factor Receptor-2 Negative Breast Cancer (HERTHENA-Breast03)
Conditions: Breast Neoplasms
Breast Cancer
Summary: Researchers are looking for new ways to treat triple-negative breast cancer (TNBC) and hormone receptor (HR) low positive/human epidermal growth factor receptor-2 (HER2) negative breast cancer. The main goals of this study are to learn:
* About the safety of the study treatments and if people tolerate them
* If people who receive patritumab deruxtecan, pembrolizumab, and chemotherapy before surgery have fewer cancer cells removed during surgery compared to those who receive only pembrolizumab (pembro) and chemotherapy.
Interventions:
description: Administered via IV infusion as neoadjuvant treatment
name: Patritumab deruxtecan
other_name: HER3-DXd
MK-1022
U3-1402
type: Biological
description: Administered via IV infusion as neoadjuvant treatment in Part 1 and via IV infusion as neoadjuvant and adjuvant treatment in Part 2
name: Pembrolizumab
other_name: KEYTRUDA®
MK-3475
type: Biological
description: Administered via IV infusion as neoadjuvant treatment
name: Paclitaxel
other_name: ONXAL®
TAXOL®
type: Drug
description: Administered via IV infusion as neoadjuvant treatment
name: Carboplatin
other_name: PARAPLATIN®
type: Drug
description: Administered via IV infusion as neoadjuvant treatment in Arm C and an option for adjuvant treatment for participants with residual disease in Arms A and B in Part 2
name: Doxorubicin hydrochloride
other_name: ADRIAMYCIN®
type: Drug
description: Administered via IV infusion as neoadjuvant treatment in Arm C and an option for adjuvant treatment for participants with residual disease in Arms A and B in Part 2
name: Epirubicin hydrochloride
other_name: ELLENCE®
type: Drug
description: Administered via IV infusion as neoadjuvant treatment in Arm C and an option for adjuvant treatment for participants with residual disease in Arms A and B in Part 2
name: Cyclophosphamide
other_name: CYTOXAN®
type: Drug
description: Administered via oral tablets as an option for adjuvant treatment for participants with residual disease in Part 2
name: Capecitabine
other_name: XELODA®
type: Drug
description: Administered via oral tablets as an option for adjuvant treatment for participants with germline BRCA mutations and residual disease in Part 2
name: Olaparib
other_name: LYNPARZA®
type: Drug
Study arms:
design_group_description: In Part 1, participants receive neoadjuvant pembrolizumab 200 mg via intravenous (IV) infusion every 3 weeks (Q3W) plus patritumab deruxtecan via IV infusion Q3W for 12 weeks, followed by pembrolizumab 200 mg via IV infusion Q3W plus paclitaxel 80 mg/m^2 via IV infusion every week (QW) and carboplatin AUC1.5 mg/ml/min via IV infusion QW for 12 weeks. At 3 to 6 weeks after last dose of neoadjuvant treatment, participants will undergo surgery for their breast cancer.
design_group_title: Part 1, A: Pembrolizimab + patritumab deruxtecan → Pembrolizumab + paclitaxel + carboplatin
design_group_type: Experimental
design_group_description: In Part 2, participants receive neoadjuvant pembrolizumab 200 mg IV infusion every Q3W plus patritumab deruxtecan (dose to be determined in part 1) IV infusion Q3W for 12 weeks, followed by pembrolizumab 200 mg IV infusion Q3W plus paclitaxel 80 mg/m^2 IV infusion QW and carboplatin AUC1.5 mg/ml/min IV infusion QW for 12 weeks. At 3-6 weeks after last dose of neoadjuvant treatment, participants undergo surgery for breast cancer. After surgery, participants receive adjuvant pembrolizumab 400 mg IV every 6 weeks (Q6W) for <br/>30 weeks. Additional adjuvant treatment of physician's choice (TPC) may be given to participants with residual disease. TPC options are olaparib 300 mg oral twice daily (BID) for 1 year (participants with germline BRCA mutation [gBRCAm] only), capecitabine 1000-1250 mg/m^2 oral BID days 1-14 and 22-35 Q6W for 4 six-week cycles or doxorubicin 60mg/m^2 (or epirubicin 90 mg/m^2) IV Q3W or every 2 weeks (Q2W) and cyclophosphamide 600 mg/m^2 IV Q3W or Q2W for 4 doses.
design_group_title: Part 2, A: Pembrolizimab + patritumab deruxtecan → Pembrolizumab + paclitaxel + carboplatin
design_group_type: Experimental
design_group_description: In Part 2, participants receive neoadjuvant pembrolizumab 200 mg IV infusion Q3W plus paclitaxel 80 mg/m^2 IV infusion QW and carboplatin AUC1.5 mg/ml/min IV infusion QW for 12 weeks, followed by pembrolizumab 200 mg IV infusion Q3W plus patritumab deruxtecan (dose to be determined in part 1) via IV infusion Q3W for 12 weeks. At 3 to 6 weeks after last dose of neoadjuvant treatment, participants will undergo surgery for their breast cancer. After surgery, participants will receive adjuvant pembrolizumab 400 mg IV infusion Q6W for <br/>30 weeks. Additional adjuvant TPC may be administered to participants with residual disease. TPC options include olaparib 300 mg oral BID for 1 year (participants with gBRCAm only), capecitabine 1000-1250 mg/m^2 oral BID days 1-14 and 22-35 Q6W for 4 six-week cycles or doxorubicin 60mg/m^2 (or epirubicin 90 mg/m^2) IV infusion Q3W or Q2W and cyclophosphamide 600 mg/m^2 IV infusion Q3W or Q2W for 4 doses.
design_group_title: Part 2, B: Pembrolizumab + paclitaxel + carboplatin → Pembrolizumab + patritumab deruxtecan
design_group_type: Experimental
design_group_description: In Part 2, participants receive neoadjuvant pembrolizumab 200 mg IV infusion Q3W plus paclitaxel 80 mg/m^2 IV infusion QW and carboplatin AUC1.5 mg/ml/min via IV infusion QW for 12 weeks, followed by pembrolizumab 200 mg IV infusion Q3W plus doxorubicin 60mg/m^2 (or epirubicin 90 mg/m^2) IV infusion Q3W and cyclophosphamide 600 mg/m^2 IV infusion Q3W for 12 weeks. At 3 to 6 weeks after last dose of neoadjuvant treatment, participants will undergo surgery for their breast cancer. After surgery, participants will receive adjuvant pembrolizumab 400 mg IV infusion Q6W for approximately 30 weeks. Additional adjuvant TPC may be administered to participants with residual disease. TPC options include olaparib 300 mg oral BID for 1 year (participants with gBRCAm only) or capecitabine 1000-1250 mg/m^2 oral BID days 1-14 and 22-35 Q6W for 4 six-week cycles.
design_group_title: Part 2, C: Pembro + paclitaxel + carboplatin→ Pembro + doxorubicin (or epirubicin) +cyclophosphamide
design_group_type: Active Comparator
Sponsor: Merck Sharp & Dohme LLC
Collaborators: Daiichi Sankyo Co., Ltd.
Drug name mappings:
name: 德帕瑞妥单抗
lang: CN
name: Patritumab Deruxtecan
lang: EN
name: 奥拉帕利
lang: CN
name: Olaparib
lang: EN
name: オラパリブ
lang: JP
name: 白蛋白结合型紫杉醇
lang: CN
name: Albumin-Bound Paclitaxel
lang: EN
name: パクリタキセル(JAN)
lang: JP
name: 环磷酰胺
lang: CN
name: Cyclophosphamide
lang: EN
name: シクロホスファミド水和物
lang: JP
name: 卡铂
lang: CN
name: Carboplatin
lang: EN
name: カルボプラチン
lang: JP
name: 盐酸多柔比星
lang: CN
name: Doxorubicin Hydrochloride
lang: EN
name: ドキソルビシン塩酸塩
lang: JP
name: 帕博利珠单抗
lang: CN
name: Pembrolizumab
lang: EN
name: ペムブロリズマブ（遺伝子組換え）
lang: JP
name: 盐酸表柔比星
lang: CN
name: Epirubicin Hydrochloride
lang: EN
name: エピルビシン塩酸塩
lang: JP
name: 卡培他滨
lang: CN
name: Capecitabine
lang: EN
name: カペシタビン
lang: JP