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

NCT06976944 | Recruiting Phase 2 DMC

• 2 other identifiers: WJOG16522BjRCT2031250076
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 14

Brief Summary

• 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.

Conditions

Recurrent Triple-Negative Breast Cancer

Keywords

Recurrent Triple-Negative; Breast Cancer; checkpoint inhibitor; angiogenesis inhibitor

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Through protocol treatment discontinuation, approximately 9 months

Secondary Outcomes (4)

• Overall response rate

  Through protocol treatment discontinuation, approximately 9 months

• Overall survival

  Through study completion, approximately 3.5 years

• Disease control rate

  Through protocol treatment discontinuation, approximately 9 months

• Incidence of adverse events

  Until 1 month after protocol treatment discontinuation, approximately 10 months

Study Arms (2)

Pembrolizumab + paclitaxel + bevacizumab

EXPERIMENTAL

Drug: Pembrolizumab; Drug: Paclitaxel; Drug: Bevacizumab

Pembrolizumab + paclitaxel

ACTIVE COMPARATOR

Drug: Pembrolizumab; Drug: Paclitaxel

Interventions

Pembrolizumab 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)

Pembrolizumab + paclitaxel; Pembrolizumab + paclitaxel + bevacizumab

Paclitaxel 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)

Pembrolizumab + paclitaxel; Pembrolizumab + paclitaxel + bevacizumab

Bevacizumab 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 + bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Yukinori Ozaki: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (14)

National Hospital Organization Nagoya Medical Center

Nagoya, Aichi-ken, 460-0001, Japan

RECRUITING

Nagoya University Hospital

Nagoya, Aichi-ken, 466-8560, Japan

RECRUITING

Nagoya City University Hospital

Nagoya, Aichi-ken, 467-8602, Japan

RECRUITING

National Cancer Center Hospital East

Kashiwa-shi, Chiba, 277-8577, Japan

RECRUITING

Gifu University Hospital

Gifu, Gifu, 501-1194, Japan

RECRUITING

Hiroshima University Hospital

Hiroshima, Hiroshima, 734-8551, Japan

RECRUITING

Hokkaido University Hospital

Sapporo, Hokkaido, 060-8648, Japan

RECRUITING

Hyogo Cancer Center

Akashi-shi, Hyōgo, 673-8558, Japan

RECRUITING

Okayama University Hospital

Okayama, Okayama-ken, 700-8558, Japan

RECRUITING

Osaka International Cancer Institute

Osaka, Osaka, 541-8567, Japan

RECRUITING

Osaka Metropolitan University Hospital

Osaka, Osaka, 545-0051, Japan

RECRUITING

Kindai University Hospital

Sakai-shi, Osaka, 590-0197, Japan

RECRUITING

Cancer Institute Hospital of JFCR

Koto-ku, Tokyo, 135-8550, Japan

RECRUITING

SHOWA Medical University Hospital

Shinagawa-ku, Tokyo, 142-8666, Japan

RECRUITING

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

pembrolizumab; Paclitaxel; Bevacizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Toshimi Takano

  Cancer Institute Hospital of JFCR

  STUDY CHAIR

Central Study Contacts

Yukinori Ozaki

CONTACT

+81-3-3520-0111; yukinori.ozaki@jfcr.or.jp

Kazuki Nozawa

CONTACT

+81-52-851-5511; k.nozawa@med.nagoya-cu.ac.jp

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Breast Medical Oncology

Study Record Dates

• First Submitted: April 30, 2025
• First Posted: May 16, 2025
• Study Start: June 24, 2025
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2029
• Last Updated: July 13, 2026

Record last verified: 2026-07

Locations

JP (14)