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

Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorYukinori Ozaki

About this trial

* 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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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 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.

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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)

  • 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)

  • 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)

Treatment groups

44 Participants
are divided into 2 treatment groups
Group A: Pembrolizumab + paclitaxel + bevacizumabExperimental treatment 3 interventions
Group B: Pembrolizumab + paclitaxelActive comparator 2 interventions

Trial outcomes

Primary outcomes

1

Progression free survival

Time frame
Through protocol treatment discontinuation, approximately 9 months

Secondary outcomes

1

Overall response rate

Time frame
Through protocol treatment discontinuation, approximately 9 months
2

Overall survival

Time frame
Through study completion, approximately 3.5 years
3

Disease control rate

Time frame
Through protocol treatment discontinuation, approximately 9 months
4

Incidence of adverse events

Time frame
Until 1 month after protocol treatment discontinuation, approximately 10 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Yukinori Ozaki

Lead sponsor

Japanese Foundation for Cancer Research

Sponsor institution

Merck Sharp & Dohme LLC

Collaborator