Clinical trial NCT06976944: Pembrolizumab + Paclitaxel +/- Bevacizumab for Triple-negative Breast Cancer
Official title: Randomized Phase II Study of Pembrolizumab + Paclitaxel +/- Bevacizumab in Patients With Recurrent Triple-Negative Breast Cancer Who Received Perioperative Immunotherapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Recurrent Triple-Negative Breast Cancer
Keywords: Recurrent Triple-Negative
Breast Cancer
checkpoint inhibitor
angiogenesis inhibitor
Lead sponsor: Japanese Foundation for Cancer Research
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2025-05-16
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 + bevacizumab therapy in PD-L1-positive triple negative breast cancer patients who relapse after receiving immune checkpoint inhibitors in the perioperative period.


Eligibility criteria: 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.

Primary outcomes:
measure: Progression free survival
timeFrame: Through protocol treatment discontinuation, approximately 9 months
Secondary outcomes:
measure: Overall response rate
timeFrame: Through protocol treatment discontinuation, approximately 9 months
measure: Overall survival
timeFrame: Through study completion, approximately 3.5 years
measure: Disease control rate
timeFrame: Through protocol treatment discontinuation, approximately 9 months
measure: Incidence of adverse events
timeFrame: Until 1 month after protocol treatment discontinuation, approximately 10 months
Other outcomes:
Locations:
city: Nagoya-shi
country: Japan
facility: National Hospital Organization Nagoya Medical Center
state: Aichi
city: Nagoya-shi
country: Japan
facility: Nagoya University Hospital
state: Aichi
city: Nagoya-shi
country: Japan
facility: Nagoya City University Hospital
state: Aichi
city: Akita-shi
country: Japan
facility: Akita University Hospital
state: Akita
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Gifu-shi
country: Japan
facility: Gifu University Hospital
state: Gifu
city: Hiroshima-shi
country: Japan
facility: Hiroshima University Hospital
state: Hiroshima
city: Sapporo-shi
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Akashi-shi
country: Japan
facility: Hyogo Cancer Center
state: Hyogo
city: Okayama-shi
country: Japan
facility: Okayama University Hospital
state: Okayama
city: Osaka-shi
country: Japan
facility: Osaka International Cancer Institute
state: Osaka
city: Sayama-shi
country: Japan
facility: Kindai University Hospital
state: Osaka
city: Koto-ku
country: Japan
facility: Cancer Institute Hospital of JFCR
state: Tokyo
city: Shinagawa-ku
country: Japan
facility: SHOWA Medical University Hospital
state: Tokyo
Study officials:
affiliation: Cancer Institute Hospital of JFCR
name: Toshimi Takano
role: STUDY_CHAIR
References: