Reinvigorating TNBC Response to Immunotherapy With Combination Myeloid Inhibition and Radiation
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexFemale
Age18+
SponsorStephen Shiao
About this trial
This is an open-label prospective, single institution, Phase II study of pembrolizumab in combination with radiation therapy and CSF-1R inhibition in patients with high-risk TNBC. The primary objective is to assess the pathologic complete response (pCR) rate where pCR is defined as the absence of invasive disease in the breast and lymph nodes at the time of standard of care (SOC) treatment. Secondary objectives include evaluating the change in tumor infiltrating lymphocytes (TILs), safety and tolerability of the combination, progression-free survival, event-free survival, overall survival, and node clearance.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Female patients diagnosed with high-risk triple negative breast cancer (TNBC) with intent for neoadjuvant therapy.
Low tumor-infiltrating lymphocyte (TIL) score, defined as stromal TIL (sTIL) ≤40%; or node-positive; or combined positive score (CPS) < 10 or PD-L1 tumor positivity <1%.
Written informed consent obtained from subject and ability for subject to comply with the requirements of the study, including consent for research blood draws and use of available archived tissue.
Age ≥ 18 years of age on day of signing informed consent.
Disqualifiers
Evidence of metastatic disease.
Has received prior radiotherapy within 2 weeks of start of study intervention.
Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
Trial design
Design model
Single group
Treatments tested in this trial
Pembrolizumab
DrugPembrolizumab 200 mg is administered intravenously at Week 1, then every 3 weeks during the treatment period (6 weeks). Therapy will continue for until initiation of SOC curative-intent treatment (neoadjuvant chemo therapy or surgery) at Week 7.
Radiation Therapy
RadiationRadiation therapy (RT) consists of 8 Gy for 3 fractions over 3 consecutive days at Week 2.
Axatilimab
DrugAxatilimab 1 mg/kg is administered intravenously weekly starting 1 week post- RT (Week 3). Therapy will continue until initiation of SOC curative-intent treatment (neoadjuvant chemo therapy or surgery) at Week 7.
Treatment groups
35 Participants
are divided into 1 treatment groupGroup A: Pembrolizumab with Radiation Therapy and AxatilimabExperimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
Pathological complete response (pCR) rate.
The proportion of patients with absence of invasive disease in the breast and lymph nodes at the time of SOC curative-intent treatment.
Time frame
From treatment start date until the time of curative-intent treatment, approximately 7 weeks.Secondary outcomes
1
Change in tumor-infiltrating lymphocytes (TILs) from biopsies.
An increase in the tumor-infiltrating lymphocyte score as measured by Salgado criteria, is an indicator of immune system engagement.
Time frame
From Week 1 and at the time of SOC curative-intent treatment, approximately 7 weeks from start of trial treatment..2
Number of adverse events related to study treatment (pembrolizumab with radiation and axatilimab).
Adverse events are graded per NCI CTCAE v.5
Time frame
From start of treatment until 1 year post-treatment.3
Event-free survival (EFS).
The length of time from the start of study treatment to the first occurrence of recurrent disease, or death due to breast cancer.
Time frame
Assessed up to 3 years.4
Overall Survival (OS).
Assessed from the start of study treatment until death due to any cause.
Time frame
From C1D1 until death, up to 3 years after end of study treatment.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Stephen Shiao
Lead sponsor
Cedars-Sinai Medical Center
Sponsor institution
Merck Sharp & Dohme LLC
Collaborator
Incyte Corporation
Collaborator
Source ClinicalTrials.gov