Converting HR+ Breast Cancer Into an Individualized Vaccine
Summary
Newly diagnosed post-menopausal women with clinical stage II-III, HR+HER2- breast cancer are eligible to a randomized trial, concurrently open at five US academic institutions. Patients receiving 4 months of standard neoadjuvant hormonal therapy with letrozole are randomly assigned to one of 4 arms of a trial testing focal hypo-fractionated RT alone or with immunotherapy combinations.
Detailed description
Patients will be on the study for a total of 5 months, this includes 4 months on active study intervention, with breast surgery at week 16 and one month follow up period, after surgery. Patients will be randomly assigned to one of these 4 arms - 1. Anti-PD1 antibody pembrolizumab (Keytruda, Merck) will be infused day 12, at the standard dose of 200 mg IV over 30 minutes, repeated every 3 weeks until disease progression or unacceptable toxicity. 2. FLT3L (CDX-301, the recombinant human protein by Celldex) will be self-administered subcutaneously, in 5 consecutive daily injections, week 1, day 1-5. 3. For all arms radiation therapy to the breast tumor will begin on week 2 (Day 8,10,12), at dose of 8 Gy x 3 fractions, every other day. 4. Letrozole (Femara ®, Novartis) 2.5 mg tabs, once a day, daily for 4 months, until surgery, and thereafter is decided by the treating physician.
Arms & interventions
- RadiationFocal Radiation therapy
Focal hypo-fractionated radiation therapy 8 Gy x 3 fractions, starting day 8, every other day (M/W/F or W/F/M or F/M/W).
- DrugPembrolizumab (200mg IV for 30 minutes
Pembrolizumab, on day 12 (last day of radiotherapy), infused over 200mg IV over 30 minutes and then repeated every 3 weeks until disease progression or unacceptable toxicity.
- BiologicalCDX-301
Ftl-3 ligand, self-administered by subcutaneous injections at week 1, daily, for 5 consecutive days.
Outcome measures
Primary
Tolerability will be demonstrated if no grade 3 or higher toxicities are observed in the first 8 patients, of each arm.
Tolerability of adding immunotherapy to a combination of tumor radiotherapy and endocrine therapy in the neoadjuvant setting of newly diagnosed HR+ breast cancer patients will be assessed if no grade 3 or higher toxicities are observed in the first 8 patients of each arm. CTCAE version 5.0 will be used.
Time frame: 3 years
Clinical response rate to tumor radiation +/-immunotherapy during standard endocrine therapy for HR+ breast cancer will be measured.
Clinical response rate to tumor radiation +/-immunotherapy during standard endocrine therapy for HR+ breast cancer will be measured.
Time frame: 3 years
Pathological response rate to tumor radiation +/-immunotherapy during standard endocrine therapy for HR+ breast cancer will be measured.
Pathological response rate to tumor radiation +/-immunotherapy during standard endocrine therapy for HR+ breast cancer will be measured.
Time frame: 3 years
Secondary
Local immune response will be measured by assessing tumor specimens for T-cell infiltration at baseline and and during treatment.
Time frame: 4 years
Systemic immune response will be measured by collecting serial blood samples for serum and peripheral blood mononuclear cells (PBMCs) at multiple time points.
Time frame: 4 years
Eligibility criteria
Study locations (8)
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Icahn School of Medicine at Mt Sinai
New York, New York, 10027
New York Presbyterian Hospital - Queens
New York, New York, 10065
Weill Cornell Medicine New York Presbyterian Hospital
New York, New York, 10065
Brooklyn Methodist Hospital - NewYork Presbyterian
New York, New York, 11215
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
UT Southwestern Medical Center
Dallas, Texas, 75390-9179
Houston Methodist Cancer Center
Houston, Texas, 77030