Durvalumab (MEDI4736) and Tremelimumab in Hormone Receptor-positive, Hypermutated Metastatic Breast Cancer Identified by Whole Exome Sequencing

NCT03608865 | Completed Phase 2

• 1 other identifier: 4-2016-0912
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Abbreviated Title : Durvalumab + tremelimumab in hypermutated breast cancer Trial Phase : II Clinical Indication : Hormone receptor-positive metastatic breast cancer Trial Type : Interventional Type of control : None Route of administration : Intravenous Trial Blinding : None Treatment Groups : Durvalumab + tremelimumab Number of trial subjects : Approximately 150 patients will be prescreened with whole exome sequencing. Then 30 patients will be enrolled in the treatment phase. Estimated enrollment period : 24 months Estimated duration of trial : The sponsor estimates that the trial will require approximately 48 months from the time the first subject signs the informed consent until the last subject's last visit. Duration of Participation : 24 months Estimated average length of treatment per patient : 8 months

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR) by RECIST 1.1

  To evaluate objective response rate (ORR) based on RECIST 1.1 in hormone receptor-positive, hypermutated metastatic breast cancer identified by whole exome sequencing (WES) Hypothesis: Durvalumab + tremelimumab in patients with hormone receptor-positive, hypermutated metastatic breast cancer identified by WES will result in clinically meaningful ORR based on RECIST 1.1

  up to 4 years (the end of study)

Secondary Outcomes (4)

• Clinical benefit rate (CBR) by RECIST 1.1 defined by complete or partial response or stable disease for at least 24 weeks

  every 1 year up to 4 years (the end of study)

• Duration of response (DoR)

  every 1 year up to 4 years (the end of study)

• Disease control rate (DCR) by RECIST 1.1

  every 1 year up to 4 years (the end of study)

• Progression-free survival (PFS) by RECIST 1.1

  every 1 year up to 4 years (the end of study)

Study Arms (1)

experimental group

EXPERIMENTAL

Drug:Durvalumab + tremelimumab Dose/Potency:Durvalumab 1500mg(up to 4cycle) / tremelimumab 75mg(up to 13 cycle) Dose Frequency:Q4W Route of Administration:IV infusion Regimen/Treatment Period:Day 1 of each 4 week cycle Use:Experimental

Drug: Durvalumab with Tremelimumab

Interventions

Durvalumab with Tremelimumab DRUG

Trial treatment should be administered on Day 1 of each cycle after all procedures/assessments have been completed as detailed on the Trial Flow Chart. Trial treatment may be administered up to 3 days before or after the scheduled Day 1 of each cycle due to administrative reasons. All trial treatments will be administered on an outpatient basis. Durvalumab 1500mg + tremelimumab 750 mg will be administered as a 60 minute each one IV infusion every 4 weeks. Sites should make every effort to target infusion timing to be as close to 60 minutes as possible. However, given the variability of infusion pumps from site to site.

experimental group

Eligibility Criteria

• Age: 19 Years+
• Gender Eligibility Details: Pre or postmenopausal women with stage IV hormone receptor-positive breast cancer by histological or cytological confirmation
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
• Pre or postmenopausal women with stage IV hormone receptor-positive breast cancer by histological or cytological confirmation
• Age \> 19 years at time of study entry
• Progression after one line of any systemic therapy (endocrine, targeted or chemotherapy) in the metastatic setting
• or more nonsynonymous mutations per megabase (Mb) by WES
• Subject who has biopsy-accessible tumor
• At least one measurable lesion by RECIST 1.1. Biopsied tumor may be counted a measurable lesion if it is not excised
• Documented disease progression on the most recent therapy
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 \~ 1
• Life expectancy of \> 12 weeks
• Adequate normal organ and marrow function as defined below:
• Haemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (\> 1500 per mm3)
• Platelet count ≥ 100 x 109/L (\>100,000 per mm3)
• Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). Previous enrollment in the present study
• Participation in another clinical study with an investigational product during the last 4 weeks
• Any previous treatment with a PD-1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA-4, including tremelimumab
• Previous or coexisting malignancies. However, malignancies that have been curatively treated \>5 years prior to study entry can be included. Exceptionally, cervical cancer in-situ, basal cell carcinoma, papillary thyroid carcinoma and superficial bladder tumors (T1a and Tis) can be included anytime after curative treatment
• Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) ≤ 21 days prior to the first dose of study drug and within 6 weeks for nitrosourea or mitomycin C) for sufficient wash-out time
• Palliative radiation, whole brain radiotherapy (WBRT), or gamma knife surgery (GKS) for brain metastases ≤ 2 weeks prior to initiation of study medication. Major surgery ≤ 4 weeks or minor surgery ≤ 2 weeks prior to initiation of study medication. Majority or minority of surgery can be decided at the investigator's discretion. Subjects who received these local therapy may be enrolled after predetermined time period
• Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia's Correction
• Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab or tremelimumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
• Any unresolved toxicity (≥CTCAE grade 2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy)
• Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE \>Grade 1
• Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
• History of primary immunodeficiency
• History of allogeneic organ transplant
• History of hypersensitivity to durvalumab or tremelimumab

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Yonsei Cancer Center, Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

durvalumab; tremelimumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Drug:Durvalumab + tremelimumab Dose/Potency: Durvalumab 1500mg(up to 4cycle) / tremelimumab 75mg(up to 13 cycle) Dose Frequency:Q4W Route of Administration:IV infusion Regimen/Treatment Period:Day 1 of each 4 week cycle Use:Experimental

Study Record Dates

• First Submitted: July 23, 2018
• First Posted: August 1, 2018
• Study Start: September 19, 2017
• Primary Completion: November 24, 2021
• Study Completion: November 24, 2021
• Last Updated: January 3, 2022

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)