Pembrolizumab + Paclitaxel +/- Bevacizumab for Triple-negative Breast Cancer

Официальное название

Randomized Phase II Study of Pembrolizumab + Paclitaxel +/- Bevacizumab in Patients With Recurrent Triple-Negative Breast Cancer Who Received Perioperative Immunotherapy

Обзор

* Breast cancer is histologically divided into non-invasive (approximately 10%) and invasive (approximately 90%), with invasive cancer being the target of chemotherapy. Invasive carcinoma is classified into four subtypes according to the expression levels of hormone receptor (HR) and human epidermal growth factor receptor type 2 (HER2). Among them, triple negative breast cancer accounts for 10% of invasive cancers and is the subtype with the poorest prognosis. * For triple negative breast cancer that is operable, chemotherapy with pembrolizumab is administered either preoperatively or postoperatively (perioperative period). For recurrent triple negative breast cancer , combination chemotherapy with multiple agents is the standard of care, especially in the case of PD-L1-positive patients, chemotherapy with an immune checkpoint inhibitor related to PD-1 (pembrolizumab or atezolizumab) is administered. * Although the KEYNOTE355 trial demonstrated the efficacy of pembrolizumab plus paclitaxel therapy in patients with PD-L1-positive triple negative breast cancer in postoperative relapse, this trial did not include patients who received pembrolizumab in the perioperative period. Therefore, it is not known if there is any benefit to re-administering pembrolizumab to these patients after relapse. * Bevacizumab is used as standard therapy for triple negative breast cancer in combination with paclitaxel. Bevacizumab itself is an anti-tumor agent that inhibits angiogenesis, but has also been reported to activate immunity against cancer, suggesting that it may enhance the effect of pembrolizumab. Based on the above, the investigators planned this trial to evaluate whether pembrolizumab + paclitaxel + bevacizumab therapy is more effective than pembrolizumab + paclitaxel therapy in PD-L1-positive triple negative breast cancer patients who relapse after receiving immune checkpoint inhibitors in the perioperative period.

Вмешательства

• Препарат Pembrolizumab
  Protocol treatment will continue until worsening of the participant's underlying disease or unacceptable toxicity is observed or the participant withdraws the consent, or the participant meets other discontinuation criteria. Pembrolizumab: Intravenous infusion(400 mg/body, every 6 weeks starting on Day 1 of Cycle 1)
• Препарат Paclitaxel
  Protocol treatment will continue until worsening of the participant's underlying disease or unacceptable toxicity is observed or the participant withdraws the consent, or the participant meets other discontinuation criteria. Paclitaxel: Intravenous infusion(90 mg/m\^2, on Days 1, 8, and 15, starting on Day 1 of Cycle 1 with a 28-day cycle)
• Препарат Bevacizumab
  Protocol treatment will continue until worsening of the participant's underlying disease or unacceptable toxicity is observed or the participant withdraws the consent, or the participant meets other discontinuation criteria. Bevacizumabl: Intravenous infusion(10 mg/kg, on Days 1, and 15, starting on Day 1 of Cycle 1 with a 28-day cycle)

Первичные конечные точки

• Progression free survival [Срок оценки: Through protocol treatment discontinuation, approximately 9 months]

Вторичные конечные точки (4)

• Overall response rate [Срок оценки: Through protocol treatment discontinuation, approximately 9 months]
• Overall survival [Срок оценки: Through study completion, approximately 3.5 years]
• Disease control rate [Срок оценки: Through protocol treatment discontinuation, approximately 9 months]
• Incidence of adverse events [Срок оценки: Until 1 month after protocol treatment discontinuation, approximately 10 months]

Критерии участия

Критерии включения

• Male/female participants who are 18 years of age or older on the day of signing informed consent with histologically or cytologically confirmed diagnosis of invasive breast cancer will be enrolled in this study.
• Participants have been confirmed to be ER negative, HER2 negative according to the latest ASCO/CAP criteria. However, it does not matter whether the result is positive or negative for PgR.
• Participants have been confirmed to be PD-L1 positive in each site's evaluation using biopsy specimen or surgical specimen.
• Participants who have received not more than 1 prior chemotherapy regimen (including those with no prior chemotherapy) for recurrent breast cancer, excluding trial drugs of this clinical trial. (Participants with prior paclitaxel or bevacizumab for recurrent breast cancer are excluded.) However, prior treatment with Olaparib for metastatic recurrence or unresectable advanced cancer in participants with BRCA gene pathogenic variant is allowed (not counted as 1 regimen).
• Participants must have recurred after treatment with an anti-PD-1/PD-L1 antibody administered as monotherapy or in combination with other ICIs or chemotherapies as a perioperative drug therapy for triple negative breast cancer.
• Have an Eastern Cooperative Oncology Group performance status of 0 to 1.

Критерии исключения

• Participants with progressive disease on RECIST or clinically diagnosed during preoperative ICI and chemotherapy.
• Known additional malignancy that is progressing or has required active treatment within the past 3 years prior to enrollment.
• Has known active CNS metastases and/or carcinomatous meningitis.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Япония · 14 центров

• National Hospital Organization Nagoya Medical Center — Nagoya
• Nagoya University Hospital — Nagoya
• Nagoya City University Hospital — Nagoya
• National Cancer Center Hospital East — Kashiwa-shi
• Gifu University Hospital — Gifu
• Hiroshima University Hospital — Hiroshima
• Hokkaido University Hospital — Sapporo
• Hyogo Cancer Center — Akashi-shi
• … и ещё 6 центров

Идентификаторы

NCT: NCT06976944 · WJOG16522B · jRCT2031250076

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗