Phase II Trial of Durvalumab (MEDI4736) and Tremelimumab in Hormone Receptor-positive, Hypermutated Metastatic Breast Cancer Identified by Whole Exome Sequencing
Overview
- Phase
- Phase 2
- Intervention
- Durvalumab with Tremelimumab
- Conditions
- Metastatic Breast Cancer
- Sponsor
- Yonsei University
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Objective response rate (ORR) by RECIST 1.1
- Status
- Completed
- Last Updated
- 4 years ago
Overview
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
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
- •2.1 or more nonsynonymous mutations per megabase (Mb) by WES
- •Subject who has biopsy-accessible tumor
- •At least one measurable lesion by RECIST 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
Exclusion Criteria
- •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
Arms & Interventions
experimental group
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
Intervention: Durvalumab with Tremelimumab
Outcomes
Primary Outcomes
Objective response rate (ORR) by RECIST 1.1
Time Frame: up to 4 years (the end of study)
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
Secondary Outcomes
- 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))
- Progression-free survival (PFS) by RECIST 1.1(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))