A Study of Novel Anti-cancer Agents in Patients With Metastatic Triple Negative Breast Cancer (BEGONIA)

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

Study Overview

• Status: Active, not recruiting
• Conditions: Triple Negative Breast Neoplasms
• Intervention / Treatment: Drug: Paclitaxel; Drug: Capivasertib; Drug: Oleclumab; Drug: Trastuzumab deruxtecan; Drug: Datopotamab deruxtecan; Drug: Durvalumab

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.

• Study Type: Interventional
• Enrollment (Actual): 243
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 5L3
      • Research Site
  • Ontario
    • London, Ontario, Canada, N6A 4L6
      • Research Site
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Research Site
    • Montreal, Quebec, Canada, H4A 3J1
      • Research Site
• Poland
  • Gdansk, Poland, 80-952
    • Research Site
  • Krakow, Poland, 31-501
    • Research Site
  • Lublin, Poland, 20-090
    • Research Site
  • Opole, Poland, 45-060
    • Research Site
  • Rzeszów, Poland, 35-021
    • Research Site
  • Warsaw, Poland, 02-781
    • Research Site
  • Warsaw, Poland, 04-141
    • Research Site
• South Korea
  • Seoul, South Korea, 03080
    • Research Site
  • Seoul, South Korea, 05505
    • Research Site
  • Seoul, South Korea, 06351
    • Research Site
• Taiwan
  • Kaohsiung City, Taiwan, 80756
    • Research Site
  • Taichung, Taiwan, 40447
    • Research Site
  • Tainan, Taiwan, 70403
    • Research Site
  • Taipei, Taiwan, 10002
    • Research Site
  • Taipei, Taiwan, 112
    • Research Site
  • Taoyuan District, Taiwan, 333
    • Research Site
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Research Site
  • London, United Kingdom, EC1M 6BQ
    • Research Site
  • Manchester, United Kingdom, M20 4BX
    • Research Site
  • Oxford, United Kingdom, OX3 7LE
    • Research Site
• United States
  • Arizona
    • Tucson, Arizona, United States, 85715
      • Research Site
  • Maryland
    • Columbia, Maryland, United States, 21044
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Research Site
    • Boston, Massachusetts, United States, 02215
      • Research Site
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Research Site
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Research Site
  • Texas
    • Dallas, Texas, United States, 75246
      • Research Site
  • Virginia
    • Williamsburg, Virginia, United States, 23188
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria

1. Female
2. At least 18 years of age at the time of screening
3. Patient must have locally confirmed advanced/unresectable or metastatic TNBC.
4. No prior treatment for metastatic (Stage IV) TNBC
5. Patient must have at least 1 lesion, not previously irradiated, that can be accurately measured
6. 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

Exclusion criteria

1. History of allogeneic organ transplantation
2. Active or prior documented autoimmune or inflammatory disorders
3. 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)
4. Untreated CNS metastases
5. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
6. Any concurrent chemotherapy, IP, or biologic therapy for cancer treatment
7. Female patients who are pregnant, breastfeeding
8. Cardiac Ejection Fraction less than 50%

Patients enrolled in Arm 2 only:

1. 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)
2. Diagnosis of diabetes mellitus Type I or diabetes mellitus Type II requiring insulin treatment.
3. 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
4. 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:

1. History of or active interstitial lung disease/pneumonitis
2. 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
3. Patients enrolled in Arm 6 only: Previously been diagnosed as HER2+ or received HER2-targeted therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; durvalumab + paclitaxel	Drug: Paclitaxel; Paclitaxel iv 4-week cycles: 3 weeks once weekly (q1w) and 1 week off; Drug: Durvalumab; Durvalumab iv Every 4 weeks (q4w) or 3 weeks (q3w) Arm 6, 7 and 8; Other Names: MEDI4736
Experimental: Arm 2; durvalumab + paclitaxel + capivasertib	Drug: Paclitaxel; Paclitaxel iv 4-week cycles: 3 weeks once weekly (q1w) and 1 week off; Drug: Capivasertib; Capivasertib oral bid 4-week cycles; 3 weeks on (dosing on days 2,3,4 and 5) and 1 week off; Other Names: AZD5363; Drug: Durvalumab; Durvalumab iv Every 4 weeks (q4w) or 3 weeks (q3w) Arm 6, 7 and 8; Other Names: MEDI4736
Experimental: Arm 5; durvalumab + paclitaxel + oleclumab	Drug: Paclitaxel; Paclitaxel iv 4-week cycles: 3 weeks once weekly (q1w) and 1 week off; Drug: Oleclumab; 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; Other Names: MEDI9447; Drug: Durvalumab; Durvalumab iv Every 4 weeks (q4w) or 3 weeks (q3w) Arm 6, 7 and 8; Other Names: MEDI4736
Experimental: Arm 6; durvalumab + trastuzumab deruxtecan	Drug: Trastuzumab deruxtecan; Trastuzumab deruxtecan iv 3-week cycles (once weekly) q3w; Other Names: DS-8201a; Drug: Durvalumab; Durvalumab iv Every 4 weeks (q4w) or 3 weeks (q3w) Arm 6, 7 and 8; Other Names: MEDI4736
Experimental: Arm 7; durvalumab + datopotamab deruxtecan	Drug: Datopotamab deruxtecan; Datopotamab deruxtecan iv 3-week cycles (once weekly) q3w; Other Names: Dato-DXd; DS-1062a; Drug: Durvalumab; Durvalumab iv Every 4 weeks (q4w) or 3 weeks (q3w) Arm 6, 7 and 8; Other Names: MEDI4736
Experimental: Arm 8; durvalumab + datopotomab deruxtecan (patients with PD-L1 positive status)	Drug: Datopotamab deruxtecan; Datopotamab deruxtecan iv 3-week cycles (once weekly) q3w; Other Names: Dato-DXd; DS-1062a; Drug: Durvalumab; Durvalumab iv Every 4 weeks (q4w) or 3 weeks (q3w) Arm 6, 7 and 8; Other Names: MEDI4736

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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)	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	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	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	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])	6 months following date of first dose

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Peter Schmid, MD, PhD, Barts Cancer Institute

Publications and helpful links

Helpful Links

• Breast Cancer Study Locator details (for US)
• Study Protocol
• SAP
• CSR Synopsis

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2018
• Primary Completion (Actual): November 29, 2024
• Study Completion (Estimated): February 26, 2027

Study Registration Dates

• First Submitted: October 25, 2018
• First Submitted That Met QC Criteria: November 14, 2018
• First Posted (Actual): November 15, 2018

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Breast Cancer; Triple Negative; TNBC; 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
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Taxoids; Cyclodecanes; Diterpenes; Paclitaxel; capivasertib; durvalumab; trastuzumab deruxtecan
• Other Study ID Numbers: D933LC00001; 2018-000764-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No