Triple Negative Breast NeoplasmsPhase 1/2BEGONIANCT03742102
A Study of Novel Anti-cancer Agents in Patients With Metastatic Triple Negative Breast Cancer
A Phase 1/2 study testing Durvalumab, Capivasertib and Oleclumab in people with Triple Negative Breast Neoplasms, run by AstraZeneca at 32 sites in 6 countries.
Trial summary
This study is designed to determine the efficacy and safety of durvalumab in combination with novel oncology therapies with or without paclitaxel and durvalumab + paclitaxel for first-line metastatic triple negative breast cancer Read more about this study
- Who is it for?
- Ages 18 to 130 years, women only
- Conditions the study is for
- Triple Negative Breast Neoplasms
- What is being tested?
- Durvalumab, Capivasertib and Oleclumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 243 participants
- Where
- 32 sitesin 6 countries
- Study dates
- 21 Dec 2018to 26 Feb 2027
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female
- At least 18 years of age at the time of screening
- Patient must have locally confirmed advanced/unresectable or metastatic TNBC.
- No prior treatment for metastatic (Stage IV) TNBC
- Patient must have at least 1 lesion, not previously irradiated, that can be accurately measured
- WHO/ECOG status at 0 or 1 at enrollment
- Patients enrolled to Arm 6 (durvalumab and DS-8201a) Must provide documentation of locally determined advanced/unresectable or metastatic TNBC with HER2 low tumor expression (IHC 2+/ISH-, IHC 1+/ISH-, or IHC 1+/ISH untested)
- Patients enrolled in Arm 8 (durvalumab + Dato-DXd) Must have PD-L1 positive tumor as determined by an IHC based assay
Who cannot join
- History of allogeneic organ transplantation
- Active or prior documented autoimmune or inflammatory disorders
- Active infection including tuberculosis, hepatitis B (known positive HBV surface antigen [HBsAg] result), hepatitis C virus (HCV), or human immunodeficiency virus (positive HIV 1/2 antibodies)
- Untreated CNS metastases
- Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
- Any concurrent chemotherapy, IP, or biologic therapy for cancer treatment
Show all 19Show fewer
- Female patients who are pregnant, breastfeeding
- Cardiac Ejection Fraction less than 50%
- Patients enrolled in Arm 2 only:
- Potent inhibitors or inducers or substrates of CYP3A4 or substrates of CYP2C9 or CYP2D6 within 2 weeks before the first dose of study treatment (3 weeks for St John's Wort)
- Diagnosis of diabetes mellitus Type I or diabetes mellitus Type II requiring insulin treatment.
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic events, such as heart failure, hypokalemia, potential for torsades de pointes, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age, or any concomitant medication known to prolong the QT interval
- Prior treatment with PI3K inhibitors, AKT inhibitors, or mammalian target of rapamycin (mTOR) inhibitors.
- Patients enrolled in Arm 5 only: History of venous thromboembolism in the past 3 months
- Patients enrolled in Arm 7 and 8 only: Clinically significant corneal disease in the opinion of the Investigator.
- Patients enrolled in Arm 6, 7 and 8 only:
- History of or active interstitial lung disease/pneumonitis
- Use of chloroquine or hydroxychloroquine in <14 days prior to Day 1 of DS-8201a (Arm 6) or Dato-DXd (DS-1062a; Arm 7 and 8) treatment
- Patients enrolled in Arm 6 only: Previously been diagnosed as HER2+ or received HER2-targeted therapy.
Trial locations and contacts
32 sites in 6 countries.
32 sites in 6 countries
United States8 sites
Research Site
Boston, Massachusetts, 02114
Research Site
Boston, Massachusetts, 02215
Research Site
Columbia, Maryland, 21044
Research Site
Dallas, Texas, 75246
Research Site
Grand Rapids, Michigan, 49503
Research Site
St Louis, Missouri, 63110
Research Site
Tucson, Arizona, 85715
Research Site
Williamsburg, Virginia, 23188
Poland7 sites
Research Site
Gdansk, 80-952
Research Site
Krakow, 31-501
Research Site
Lublin, 20-090
Research Site
Opole, 45-060
Research Site
Rzeszów, 35-021
Research Site
Warsaw, 02-781
Research Site
Warsaw, 04-141
Taiwan6 sites
Research Site
Kaohsiung City, 80756
Research Site
Taichung, 40447
Research Site
Tainan, 70403
Research Site
Taipei, 10002
Research Site
Taipei, 112
Research Site
Taoyuan, 333
Canada4 sites
Research Site
Greenfield Park, Quebec, J4V 2H1
Research Site
Kelowna, British Columbia, V1Y 5L3
Research Site
London, Ontario, N6A 4L6
Research Site
Montreal, Quebec, H4A 3J1
United Kingdom4 sites
Research Site
Cambridge, CB2 0QQ
Research Site
London, EC1M 6BQ
Research Site
Manchester, M20 4BX
Research Site
Oxford, OX3 7LE
South Korea3 sites
Research Site
Seoul, 03080
Research Site
Seoul, 05505
Research Site
Seoul, 06351
About this study
Official title: A Phase IB/II, 2-stage, Open-label, Multicenter Study to Determine the Efficacy and Safety of Durvalumab (MEDI4736) + Paclitaxel and Durvalumab (MEDI4736) in Combination With Novel Oncology Therapies With or Without Paclitaxel for First-line Metastatic Triple Negative Breast Cancer
This study is designed to determine the efficacy and safety of durvalumab in combination with novel oncology therapies with or without paclitaxel and durvalumab + paclitaxel for first-line metastatic triple negative breast cancer
Read the detailed description
This is a Phase IB/II, 2-stage, open-label, multicenter study to determine the efficacy and safety of durvalumab in combination with novel oncology therapies (i.e. therapies designed for immune modulation) with or without paclitaxel and durvalumab + paclitaxel as first-line treatment in patients with metastatic triple negative breast cancer (TNBC). The study is designed to concurrently evaluate potential novel treatment combinations with clinical promise using a 2-stage approach. The study will use a Simon 2-Stage design to evaluate which cohorts may proceed to expansion.
Part 1 is a Phase IB study of safety and initial efficacy, and Part 2 may expand patient enrollment if adequate efficacy signal is observed in Part 1. The treatment regimens evaluated in Part 2 will depend on the evaluation of safety and efficacy outcomes in Part 1.
- Conditions
- Triple Negative Breast Neoplasms
- Being tested
- Durvalumab, Capivasertib, Oleclumab, Paclitaxel, Trastuzumab deruxtecan
- Keywords
- Breast Cancer, TNBC, Triple Negative, Triple Negative Breast Cancer, Triple-Negative Breast Cancer, Triple-Negative Breast Neoplasm, ER-Negative PR-Negative HER2-Negative Breast Cancer, ER-Negative PR-Negative HER2-Negative Breast Neoplasms, PD-L1 high TNBC
- Medical subject headings
- Triple Negative Breast Neoplasms, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DurvalumabDrug
Also called MEDI4736
Durvalumab iv Every 4 weeks (q4w) or 3 weeks (q3w) Arm 6, 7 and 8
CapivasertibDrug
Also called AZD5363
Capivasertib oral bid 4-week cycles; 3 weeks on (dosing on days 2,3,4 and 5) and 1 week off
OleclumabDrug
Also called MEDI9447
Oleclumab iv Every 2 weeks (q2w) for first 2 cycles (days 1 and 15 in cycles 1 and 2), then every 4 weeks (q4w) starting at cycle 3 day 1
PaclitaxelDrug
Paclitaxel iv 4-week cycles: 3 weeks once weekly (q1w) and 1 week off
Trastuzumab deruxtecanDrug
Also called DS-8201a
Trastuzumab deruxtecan iv 3-week cycles (once weekly) q3w
Datopotamab deruxtecanDrug
Also called Dato-DXd; DS-1062a
Datopotamab deruxtecan iv 3-week cycles (once weekly) q3w
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | durvalumab + paclitaxel Receives: Drug: Durvalumab; Drug: Paclitaxel |
| Arm 2 | Experimental | durvalumab + paclitaxel + capivasertib Receives: Drug: Durvalumab; Drug: Capivasertib; Drug: Paclitaxel |
| Arm 5 | Experimental | durvalumab + paclitaxel + oleclumab Receives: Drug: Durvalumab; Drug: Oleclumab; Drug: Paclitaxel |
| Arm 6 | Experimental | durvalumab + trastuzumab deruxtecan Receives: Drug: Durvalumab; Drug: Trastuzumab deruxtecan |
| Arm 7 | Experimental | durvalumab + datopotamab deruxtecan Receives: Drug: Durvalumab; Drug: Datopotamab deruxtecan |
| Arm 8 | Experimental | durvalumab + datopotomab deruxtecan (patients with PD-L1 positive status) Receives: Drug: Durvalumab; Drug: Datopotamab deruxtecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limiting Toxicity (DLT) Events
The occurrence of a severe adverse event (meeting pre-specified criteria) that is at least possibly related to durvalumab and/or the novel oncology therapy in 6 DLT-evaluable patients
Measured: From the time of first dose until completion of the first cycle (28 days for Arms 2-5, 21 days for Arms 6-7 (no safety run-in for Arms 1 and 8))
Secondary outcomes (6)
Objective Response Rate (ORR)
Percentage of evaluable patients with a confirmed Investigator-assessed response of CR (complete response) or PR (partial response). Confirmed response is defined as at least one visit response of CR or PR confirmed by a follow-up scan at least 4 weeks later showing CR or PR.
Measured: Tumor assessments: every 8 wks (Arms 1-5) or every 6 wks (Arms 6-8) until wk 48, then every 12 wks from first IP dose until radiologic progression, death, withdrawal of consent, or study completion; up to max 54 mos (observed longest duration in Arm 1)
Progression-free Survival (PFS)
Time from date of first dose (at least one study intervention [durvalumab, paclitxel or novel oncology therapy]) until the date of objective radiological disease progression using RECIST 1.1 or death (by any cause in the absence of progression)
Measured: Tumor assessments: every 8 wks (Arms 1-5) or every 6 wks (Arms 6-8) until wk 48, then every 12 wks from first IP dose until radiologic progression, death, withdrawal of consent, or study completion; up to max 54 mos (observed longest duration in Arm 1)
Duration of Response (DoR)
Time from the date of first documented response (which is subsequently confirmed) until the first date of documented progression (PD) or death in the absence of PD (ie, date of PFS event or censoring - date of first response + 1). If a patient does not progress following a response, then their DoR will be censored at the last evaluable disease assessment date
Measured: Tumor assessments: every 8 wks (Arms 1-5) or every 6 wks (Arms 6-8) until wk 48, then every 12 wks from first IP dose until radiologic progression, death, withdrawal of consent, or study completion; up to max 54 mos (observed longest duration in Arm 1)
Overall Survival (Count)
Number of patients with overall survival, the time from date of first dose (at least one study intervention [durvalumab, paclitxel or novel oncology therapy]) until the date of death by any cause
Measured: From date of first dose until date of death due to any cause; up to the maximum of 54 months (observed longest duration in Arm 1)
Overall Survival (Duration)
Time from date of first dose (at least one study intervention [durvalumab, paclitxel or novel oncology therapy]) until the date of death by any cause
Measured: From date of first dose of IP until date of death due to any cause; up to the maximum of 54 months (observed longest duration in Arm 1)
Progression-free Survival at 6 Months (PFS6)
Percentage of patients alive and progression-free at 6 months following date of first dose (at least one study intervention [durvalumab, paclitxel or novel oncology therapy])
Measured: 6 months following date of first dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2018
- Study start21 Dec 2018
- Primary completion29 Nov 2024
- Study completion26 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Triple Negative Breast NeoplasmsStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Part 1: At least 20 patients in the durvalumab-paclitaxel arm and at least 30 patients in each of the other novel treatment combination arms will be enrolled, for a total of approximately 140 patients (durvalumab + paclitaxel arm and 4 novel treatment combination arms). Additional patients may be enrolled in order to have 20 or 30 evaluable (i.e. dosed) patients per durvalumab - paclitaxel arm or novel treatment combination arm, respectively. Part 2: Approximately 27 patients will be assigned to each treatment arm, for an anticipated total of 57 response-evaluable patients per arm (ie, 30 patients in Part 1 and 27 patients in Part 2 per treatment arm, with the exception of Arm 1, which will enroll 20 patients in Part 1 and will not be expanded to Part 2). Patient expansion from 30 patients in Part 1 to an additional 27 patients from Part 2 will be determined based on a futility analysis utilizing a Simon 2 Stage design.
- Masking
- None (open label)
- Enrolment
- 243 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Peter Schmid, MD, PhD, Principal investigator, Barts Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03742102
- Sponsor's protocol ID
- D933LC00001
- Other IDs
- 2018-000764-29, 2018
- Acronym
- BEGONIA
- Status last verified
- Aug 2026
- First submitted
- 25 Oct 2018
- Last updated
- 4 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Publications
Schmid P, Im SA, Nowecki Z, Wysocki PJ, Jassem J, Jung KH, Lord S, Armstrong J, Stewart R, Vukovic P, Denduluri N, Park YH. First-line durvalumab in combination with trastuzumab deruxtecan in women with locally advanced unresectable or metastatic, hormone-receptor-negative, HER2-low breast cancer: multicenter, open-label, phase 1b/2 BEGONIA platform trial. Nat Cancer. 2026 Jun;7(6):983-992. doi: 10.1038/s43018-026-01181-8. Epub 2026 Jun 8.
PubMed 42259988