Combination of Pembrolizumab With Oral Metronomic Cyclophosphamide in Patients With Chest Wall Breast Cancer (PERICLES): A Phase II Study
This is a Phase II single center, open-label, non-randomized study in patients with locally recurrent, inoperable, and/or metastatic inflammatory breast cancer with lymphangitic spread to the chest wall. Patients will be treated with pembrolizumab administered as an intravenous infusion at 200 mg in 21-day treatment cycles and oral cyclophosphamide (CTX) 50 mg per day in metronomic administration as a 21 days cycle Forty-six patients will be required for the study. Key inclusion criteria are PDL1 (≥1%) positive and/or tumor infiltrating lymphocyte positive (≥1%) locally advanced chest wall breast cancer (with or without distant metastases), who have been treated with chemotherapy or radiation therapy may be eligible for this study. Patients with cutaneous metastases only (with or without evidence of primary tumor) are eligible for the study. Key exclusion criteria included prior anti PD1 or anti CTLA-4 or other immune pathway-targeted therapy. Patients with autoimmune diseases and/or receiving drugs who interfere with the immune system will not be eligible.
• Histologically proven, PDL1 (≥1%) positive and/or tumor infiltrating lymphocytes (TILs) positive (≥1%), locally advanced chest wall breast cancer (with or without distant metastases), who have been treated with chemotherapy or radiation therapy may be eligible for this study. Patients with cutaneous metastases only (with or without evidence of primary tumor) are also eligible;
• Patients must have tissue accessible for serial biopsies;
• Expected survival of \> 3 months;
• Be willing and able to provide written informed consent/assent for the trial. The subject may also provide consent/assent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor;
• Be 18 years of age on day of signing informed consent;
• Be a female or male subject with IBC with lymphangitic spread to the chest wall. ER, PgR and HER2 status determination is required for enrollment;
• Have provided tissue for PD-L1 biomarker analysis from a newly obtained core or excisional biopsy of a tumor lesion (mandatory) and received permission for enrollment from the Core Lab based on the adequacy of the biopsy specimen. Repeat samples may be required if adequate tissue is not provided;
• Have measurable metastatic disease based on irRECIST criteria as determined by central radiology review. Tumor lesions situated in a previously irradiated area are considered measurable, if progression has been demonstrated in such lesions. Note: The exact same image acquisition and processing parameters should be used throughout the study;
• Have a performance status of 0 or 1 on the ECOG Performance Scale. Assessment should be performed within 10 days of treatment initiation;
• Female subjects of childbearing potential (Section 2.9.2) must be willing to use an adequate method of contraception as outlined in Section 2.9.2 - Contraception, for the course of the study through 120 days after the last dose of study medication;
• Male subjects childbearing potential (Section 2.9.2) must agree to use an adequate method of contraception as outlined in Section 2.9.2- Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject;
• Female subjects of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required;
• Patients with hormone receptor-positive and/or HER2-positive breast cancer would be eligible for the study only if their disease is considered refractory to hormonal or anti-HER2 agents, respectively, and no further hormonal or anti-HER2 treatment is indicated;
• Demonstrate adequate organ function as defined in protocol, all screening labs should be performed within 10 days of treatment initiation;
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required;
• Female subjects of childbearing potential (Section 5.7.2) must be willing to use an adequate method of contraception as outlined in Section 5.7.2 - Contraception, for the course of the study through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject;
• Male subjects of childbearing potential (Section 5.7.1) must agree to use an adequate method of contraception as outlined in Section 5.7.1- Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.