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

NCT ID: NCT06976944

Last Updated: 2025-07-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

44 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-07-31

Study Completion Date

2028-09-30

Brief Summary

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* 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.

Detailed Description

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Conditions

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Recurrent Triple-Negative Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Pembrolizumab + paclitaxel + bevacizumab

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type DRUG

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)

Paclitaxel

Intervention Type DRUG

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)

Bevacizumab

Intervention Type DRUG

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)

Pembrolizumab + paclitaxel

Group Type ACTIVE_COMPARATOR

Pembrolizumab

Intervention Type DRUG

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)

Paclitaxel

Intervention Type DRUG

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)

Interventions

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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)

Intervention Type DRUG

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)

Intervention Type DRUG

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)

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. 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.
2. 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.
3. Participants have been confirmed to be PD-L1 positive in each site's evaluation using biopsy specimen or surgical specimen.
4. Participants who have not undergone chemotherapy for recurrent breast cancer. However, prior treatment of Olaparib for metastatic recurrence or unresectable advanced cancer in participants with BRCA gene pathogenic variant is allowed.
5. 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.
6. Have an Eastern Cooperative Oncology Group performance status of 0 to 1.

Exclusion Criteria

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

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

Yukinori Ozaki

OTHER

Sponsor Role lead

Responsible Party

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Yukinori Ozaki

Director of Breast Medical Oncology

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Toshimi Takano

Role: STUDY_CHAIR

Cancer Institute Hospital of JFCR

Locations

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National Hospital Organization Nagoya Medical Center

Nagoya, Aichi-ken, Japan

Site Status RECRUITING

Nagoya University Hospital

Nagoya, Aichi-ken, Japan

Site Status RECRUITING

Nagoya City University Hospital

Nagoya, Aichi-ken, Japan

Site Status NOT_YET_RECRUITING

Akita University Hospital

Akita, Akita, Japan

Site Status NOT_YET_RECRUITING

National Cancer Center Hospital East

Kashiwa-shi, Chiba, Japan

Site Status NOT_YET_RECRUITING

Gifu University Hospital

Gifu, Gifu, Japan

Site Status RECRUITING

Hiroshima University Hospital

Hiroshima, Hiroshima, Japan

Site Status NOT_YET_RECRUITING

Hokkaido University Hospital

Sapporo, Hokkaido, Japan

Site Status RECRUITING

Hyogo Cancer Center

Akashi-shi, Hyōgo, Japan

Site Status RECRUITING

Okayama University Hospital

Okayama, Okayama-ken, Japan

Site Status RECRUITING

Osaka International Cancer Institute

Osaka, Osaka, Japan

Site Status RECRUITING

Osaka Metropolitan University Hospital

Osaka, Osaka, Japan

Site Status NOT_YET_RECRUITING

Kindai University Hospital

Sayama-shi, Osaka, Japan

Site Status NOT_YET_RECRUITING

Cancer Institute Hospital of JFCR

Koto-ku, Tokyo, Japan

Site Status RECRUITING

SHOWA Medical University Hospital

Shinagawa-ku, Tokyo, Japan

Site Status RECRUITING

Countries

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Japan

Central Contacts

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Yukinori Ozaki

Role: CONTACT

+81-3-3520-0111

Kazuki Nozawa

Role: CONTACT

+81-52-851-5511

Facility Contacts

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Chiyoe Kitagawa

Role: primary

+81-52-951-1111

Madoka Iwase

Role: primary

+81-52-741-2111

Kazuki Nozawa

Role: primary

+81-52-851-5511

Kaori Terata

Role: primary

+81-18-834-1111

Chikako Funasaka

Role: primary

+81-4-7133-1111

Manabu Futamura

Role: primary

+81-58-230-6000

Hideo Shigematsu

Role: primary

+81-82-257-5555

Masato Takahashi

Role: primary

+81-11-716-1161

Koji Matsumoto

Role: primary

+81-78-929-1151

Yuko Takahashi

Role: primary

+81-86-235-6835

Takahiro Nakayama

Role: primary

+81-6-6945-1181

Shinichiro Kashiwagi

Role: primary

+81-6-6645-2121

Tsutomu Iwasa

Role: primary

+81-72-366-0221

Toshimi Takano

Role: primary

+81-3-3520-0111

Hitomi Sakai

Role: primary

+81-3-3784-8000

Other Identifiers

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jRCT2031250076

Identifier Type: REGISTRY

Identifier Source: secondary_id

WJOG16522B

Identifier Type: -

Identifier Source: org_study_id

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