Phase II Trial of Pembrolizumab and Paclitaxel in Hormone Receptor-positive, hyperMUTATted Metastatic Breast Cancer Identified by Whole exOme sequeNcing ('MUTATION2')

Yonsei University1 site in 1 country52 target enrollmentJuly 2021

ConditionsBreast Cancer

InterventionsPembrolizumab 200mg +Paclitaxel 80mg/m2

DrugsPembrolizumab 200mg +Paclitaxel 80mg/m2

Overview

Phase: Phase 2
Intervention: Pembrolizumab 200mg +Paclitaxel 80mg/m2
Conditions: Breast Cancer
Sponsor: Yonsei University
Enrollment: 52
Locations: 1
Primary Endpoint: Objective response rate (ORR) by RECIST 1.1
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

Abbreviated Title :Pembrolizumab with paclitaxel in hypermutated breast cancer Trial Phase: Phase II Clinical Indication: Hormone receptor-positive metastatic breast cancer Trial Type: Interventional Type of control: None Route of administration: Intravenous Trial Blinding: None Treatment Groups : Pembrolizumab plus paclitaxel Number of trial participants: Approximately 200 patients will be prescreened with whole exome sequencing. Then 52 patients will be enrolled in the treatment phase.

Estimated enrollment period :12 months Estimated duration of trial :The sponsor estimates that the trial will require approximately 24 months from the time the first subject signs the informed consent until the last subject's last visit.

Duration of Participation :24 months Estimated average length of treatment per patient :8 months

Registry

clinicaltrials.gov

Start Date

July 2021

End Date

December 2022

Last Updated

4 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Yonsei University

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Male participants or female participants who are pre or postmenopausal women and at least 19 years of age on the day of signing informed consent with histologically or cytologically confirmed diagnosis of stage IV hormone receptor-positive breast cancer will be enrolled in this study.
•A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
•Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
•a WOCBP must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 120 days, corresponding to time needed to eliminate any study treatments \[e.g., 5 terminal half-lives for pembrolizumab and paclitaxel (52.7 hours)\] after the last dose of study treatment.
•No prior systemic cytotoxic chemotherapy in the metastatic setting. Lines of endocrine or HER2-targeted therapy are not limited.
•\* No prior paclitaxel, except ≥12 months after last dose of chemotherapy for early breast cancer (if chemotherapy given)
•Criteria of hypermutation should be met.
•\*Criteria of hypermutation: 70 nonsynonymous mutations per tumor per exome as the presumptive starting cut-off for upper 20% of mutation burden. we will revise cut-off after enrolling every 30 patients. That is, the criteria of hypermutation will be altered every 30 cases.
•The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
•Have measurable disease based on RECIST 1.

Exclusion Criteria

•A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
•Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
•Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks \[could consider shorter interval for kinase inhibitors or other short half-life drugs\] prior to allocation.
•Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
•Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
•Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
•Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
•Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
•Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
•Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or other in-situ cancers

Arms & Interventions

Single Arm

Pembrolizumab is a potent humanized immunoglobulin G4 (IgG4) monoclonal antibody (mAb) with high specificity of binding to the programmed cell death 1 (PD-1) receptor.

Intervention: Pembrolizumab 200mg +Paclitaxel 80mg/m2

Outcomes

Primary Outcomes

Objective response rate (ORR) by RECIST 1.1

Time Frame: up to 24 months(RECIST will be done every 8 weeks)

rate of patients with complete remission (CR) or partial remission (PR) based on RESIST1.1

Secondary Outcomes

Incidence of AE by CTCAE 5.0(up to 24 months)
Clinical benefit rate (CBR) by RECIST 1.1(up to 24 months(RECIST will be done every 8 weeks))
Duration of response (DoR)(up to 24 months(RECIST will be done every 8 weeks))
Disease control rate (DCR) by RECIST 1.1(up to 24 months(RECIST will be done every 8 weeks))
Progression-free survival (PFS) by RECIST 1.1(up to 24 months(RECIST will be done every 8 weeks))