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Phase 1

• Conditions: Patients with ER+ and HER2- primary non-metastatic breast cancer who are eligible to neoadjuvant endocrine therapy.; MedDRA version: 19.0Level: PTClassification code 10006187Term: Breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-000764-42-FR
• Lead Sponsor: ICANCER

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-11-23
• Last Update Posted: 7 September 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: Not specified

Inclusion Criteria

1. Age =18 years post-menopausal according to the following criteria:
Age > 60 years
Bilateral ovariectomy
Age = 60, with an uterus and presenting an amenorrhea of more than 12 months
Age = 60, without an uterus and FSH > 20 IU/L
2. Histologically proven invasive breast cancer eligible to neoadjuvant endocrine therapy according to multidisciplinary tumor board;
Note: Multicentric/multifocal tumors are allowed if all share the same characteristics.
3. cT2-T4, any N; cT2 are eligible only if the clinical tumor size is > 3cm
4. Non metastatic, M0 (according to clinical staging);
5. ER-positive by IHC according to local assessment;
6. Her2-negative by IHC (score 0 or 1+) and/or FISH/CISH negative according to local assessment;
7. CD8+ T Cell infiltration defined as >10% cells stained with anti-CD8 mAB by IHC at the 3-week biopsy (applicable for inclusion in part 2 only);
8. Available tumor samples from baseline biopsy;
9. World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrolment;
10. Adequate organ and marrow function as defined below:
Hemoglobin =9.0 g/dL
Absolute neutrophil count =1.5 × 109 /L
Platelet count =100 × 109/L
Serum bilirubin =1.5 × the ULN. This will not apply to patients with confirmed Gilbert’s syndrome, who will be allowed in consultation with their physician.
ALT and AST =2.5 × ULN;
Calculated creatinine clearance >50 mL/min as determined by Cockcroft-Gault (using actual body weight)
Males: Creatinine CL (mL/min) =Weight (kg) × (140 - Age) /(72 × serum creatinine (mg/dL))
Females: Creatinine CL (mL/min) =Weight (kg) × (140 - Age) × 0.85 / (72 × serum creatinine (mg/dL))
11. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures;
12. Written informed consent obtained prior to performing any protocol-related procedures, including screening evaluations.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 120
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 120

Exclusion Criteria

1. No prior exposure to immune-mediated therapy including, but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand 2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines;

2. Any concurrent chemotherapy, investigational product (IP), biologic therapy for cancer treatment;

3. Previous Radiotherapy treatment to more than 30% of the bone marrow;

4. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose;

5. History of allogenic organ transplantation;

6. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn’s disease], diverticulitis with the exception of diverticulosis, celiac disease or other serious gastrointestinal chronic conditions associated with diarrhea), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis), Graves’ disease, rheumatoid arthritis, hypophysitis, uveitis, etc within the past 3 years prior to the start of treatment. The following are exceptions to this criterion:
- Patients with vitiligo or alopecia
- Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement or psoriasis not requiring systemic treatment;

7. Any condition that, in the opinion of the Investigator, would interfere with the evaluation of investigational product or interpretation of patient safety or study results, including ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events from investigational products, or compromise the ability of the patient to give written informed consent;

8. Mean QT interval corrected for heart rate using Fridericia’s formula (QTcF) =470 ms;

9. History of active primary immunodeficiency;

10. Known history of active tuberculosis;

11. Active infection including hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)

12. Current or prior use of immunosuppressive medication within 14 days before the first dose. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection).
- Systemic corticosteroids at physiologic doses not exceeding 10 mg/day of prednisone or its equivalent
- Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)

13. Receipt of live, attenuated vaccine within 30 days prior to the first dose of IP.
Note: Patients, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of IP.

14. Known allergy or hypersensitivity to IP or any excipient

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified