Durvalumab and Endocrine Therapy in ER+/Her2- Breast Cancer After CD8+ Infiltration Effective Immune-Attractant Exposure (ULTIMATE)
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|ClinicalTrials.gov Identifier: NCT02997995|
Recruitment Status : Completed
First Posted : December 20, 2016
Last Update Posted : September 30, 2020
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer Estrogen Receptor Positive Tumor Menopause Hormone Antagonist||Drug: Immune-attractant Drug: Durvalumab Procedure: Biopsy||Phase 2|
The study is conducted in 2 parts:
Part 1: lymphocyte attraction. After the screening phase, the patient will receive immune-attractant combined with exemestane for six weeks.
As immune-attractants are added over the course of the study, they will appear as subsequent appendices in the full protocol.
Up to 4 cohorts may be tested sequentially in this design until up to 240 evaluable patients have been treated.
The first cohort of patients will receive tremelimumab (3 mg/kg, single infusion) combined with exemestane (25 mg daily). In each cohort, an interim analysis will be performed after 30 patients in order to potentially stop the cohort (if less than 25% of patients present >10% CD8+ cells in the tumor after 3 weeks). If all 4 cohorts are closed and the target number of 56 patients for part 2 has not been reached, additional patients will be recruited and treated with the best performing immune-attractant treatment based on the part I results. From the moment 56 patients are included in part 2, no more patients will be entered in part 1.
After three weeks (+/- 3 days), a tumor biopsy will be done. Patients who present >10% CD8+ cells in the tumor after 3 weeks and remain eligible will be included in the second part of the trial (patients who do not present CD8+ T cells on the 3-week biopsy will be treated at the investigator's choice).
Part 2: lymphocyte activation (anti-PD1 treatment) Four to six weeks after immune-attractant start, patients having >10% CD8+ cells in the tumor will receive durvalumab 1500 mg Q4W (equivalent to 20 mg/kg Q4W) IV, combined with exemestane (25 mg daily), for six months.
Part 2 will include two steps. In the first step, we will include 23 patients. If 2 or more pathological complete responses are observed in these 23 patients, the part 2 will move to step 2. 33 additional patients will be included in the step 2.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||61 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Trial Testing Durvalumab Combined With Endocrine Therapy in Patients With ER+/Her2- Breast Cancer Eligible for Neoadjuvant Endocrine Therapy And Who Present CD8+ T Cell Infiltration After 4-6 Weeks Exposure to Immune-Attractant|
|Actual Study Start Date :||February 15, 2017|
|Actual Primary Completion Date :||July 15, 2019|
|Actual Study Completion Date :||August 28, 2020|
Experimental: Immune-attractant/lymphocyte activation
After the screening phase, the patient will receive immune-attractant combined with exemestane for six weeks. After three weeks (+/- 3 days), a tumor biopsy will be done. Patients who present >10% CD8+ cells in the tumor after 3 weeks and remain eligible will be included in the second part of the trial i.e. lymphocyte activation. In this second part, patients will receive durvalumab 1500 mg Q4W (equivalent to 20 mg/kg Q4W) IV, combined with exemestane (25 mg daily), for six months. The pathological response will be checked by surgery.
The first cohort patients will receive tremelimumab (3 mg/kg, single infusion) as immune-attractants combined with exemestane (25 mg daily).
Other Name: Tremelimumab
Durvalumab (lymphocyte activation) will be administrated at a dose of 1500 mg Q4W (equivalent to 20 mg/kg Q4W) IV, combined with exemestane (25 mg daily), for six months
Other Name: MEDI4736
After three weeks (+/- 3 days) of immune-attractants, a tumor biopsy will be done. Patients who present >10% CD8+ cells in the tumor after 3 weeks will receive the Durvalumab
- pathological Complete Response [ Time Frame: at time of surgery ]Response at surgery
- Number of CD8+ T cell [ Time Frame: at biopsy (3 weeks) ]exam at biopsy and comparison between biopsy and Baseline biopsy rates
- Clinical response [ Time Frame: after 6 months of Durvalumab ]Clinical exam
- Assessment of Ki67 [ Time Frame: at surgery ]measure of Ki67
- Toxicities [ Time Frame: 1 year and 8 months ]Common terminology criteria for adverse events (CTC-AE) v4.03
- Predictive value of Mutational load for efficacy of Durvalumab [ Time Frame: on baseline biopsy and blood samples ]exome sequencing on baseline samples
- Predictive value of PDL1 expression for the efficacy of Durvalumab [ Time Frame: on baseline biopsy and biopsy at 3 weeks ]correlate Immune infiltrate intensity with the proportion of tumor cells expressing PD-L1 by Ventana SP263 assay
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02997995
|Principal Investigator:||Fabrice Andre, Prof||Gustave Roussy, Cancer Campus, Grand Paris|