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: 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 (Estimated): 240
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: AZ Breast Cancer Study Navigators AZ Breast Cancer Study Navigators; Phone Number: +1-877-400-4656; Email: AstraZeneca@CareboxHealth.com
• Study Contact Backup: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Canada
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 5L3
      • Terminated
      • Research Site
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Active, not recruiting
      • Research Site
    • Toronto, Ontario, Canada, M4N 3M5
      • Withdrawn
      • Research Site
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Active, not recruiting
      • Research Site
    • Montreal, Quebec, Canada, H4A 3J1
      • Recruiting
      • Research Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 05505
    • Recruiting
    • Research Site
  • Seoul, Korea, Republic of, 06351
    • Recruiting
    • Research Site
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Research Site
• Poland
  • Gdańsk, Poland, 80-214
    • Active, not recruiting
    • Research Site
  • Gliwice, Poland, 44-101
    • Withdrawn
    • Research Site
  • Kraków, Poland, 31-501
    • Active, not recruiting
    • Research Site
  • Lublin, Poland, 20-090
    • Active, not recruiting
    • Research Site
  • Opole, Poland, 45-060
    • Active, not recruiting
    • Research Site
  • Poznań, Poland, 61-848
    • Withdrawn
    • Research Site
  • Rzeszów, Poland, 35-021
    • Active, not recruiting
    • Research Site
  • Warszawa, Poland, 02-781
    • Active, not recruiting
    • Research Site
  • Warszawa, Poland, 04-141
    • Completed
    • Research Site
• Taiwan
  • Kaohsiung, Taiwan, 80756
    • Recruiting
    • Research Site
  • Taichung, Taiwan, 40447
    • Recruiting
    • Research Site
  • Tainan City, Taiwan, 70403
    • Recruiting
    • Research Site
  • Taipei, Taiwan, 10002
    • Recruiting
    • Research Site
  • Taipei, Taiwan, 112
    • Recruiting
    • Research Site
  • Taoyuan, Taiwan, 333
    • Recruiting
    • Research Site
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Active, not recruiting
    • Research Site
  • London, United Kingdom, EC1M 6BQ
    • Active, not recruiting
    • Research Site
  • London, United Kingdom, W1T 7HA
    • Withdrawn
    • Research Site
  • Manchester, United Kingdom, M20 4BX
    • Active, not recruiting
    • Research Site
  • Oxford, United Kingdom, OX3 7LE
    • Active, not recruiting
    • Research Site
• United States
  • Arizona
    • Goodyear, Arizona, United States, 85395
      • Recruiting
      • Research Site
    • Tucson, Arizona, United States, 85715
      • Terminated
      • Research Site
  • California
    • West Hollywood, California, United States, 90048
      • Withdrawn
      • Research Site
  • Maryland
    • Columbia, Maryland, United States, 21044
      • Recruiting
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Research Site
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Research Site
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Recruiting
      • Research Site
  • Minnesota
    • Saint Paul, Minnesota, United States, 55102
      • Recruiting
      • Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Research Site
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Withdrawn
      • Research Site
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Recruiting
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19124
      • Withdrawn
      • Research Site
  • Texas
    • Dallas, Texas, United States, 75246
      • Recruiting
      • Research Site
    • Flower Mound, Texas, United States, 75028
      • Recruiting
      • Research Site
    • Houston, Texas, United States, 77030
      • Withdrawn
      • Research Site
    • McAllen, Texas, United States, 78503
      • Recruiting
      • Research Site
    • San Antonio, Texas, United States, 78240
      • Withdrawn
      • Research Site
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Withdrawn
      • Research Site
    • Williamsburg, Virginia, United States, 23188
      • Recruiting
      • 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
Incidence of adverse events	Part 1: Assessment of safety and tolerability of each treatment arm Part 2: Endpoints based on Investigator assessment according to RECIST 1.1: ORR (objective response rate): The percentage of evaluable patients with a confirmed Investigator-assessed visit response of CR (complete response) or PR (partial response).	Part1: From informed consent until the safety follow-up visit 3 months after the last dose of study drug. Part 2: From informed consent until the safety follow-up visit 3 months after the last dose of study drug.
Laboratory findings	Assessment of safety and tolerability of each treatment arm	Part 1: From informed consent until the safety follow-up visit 3 months after the last dose of study drug. Part 2:From informed consent until the safety follow-up visit 3 months after the last dose of study drug.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	Assessment of the efficacy of each treatment arm according to RECIST 1.1. ORR: The percentage of evaluable patients with a confirmed Investigator-assessed response of CR (complete response) or PR (partial response) Applicable for Part 1 and Part 2.	Approx. 30 months
Overall survival (OS)	OS: Time from date of first dose until the date of death by any cause Applicable for Part 1 and Part 2	Approx. 30 months
Progression-free survival (PFS).	Assessment of the efficacy of each treatment arm according to RECIST 1.1. PFS: Time from date of first dose until the date of objective radiological disease progression or death (by any cause in the absence of progression) Applicable for Part 1 and Part 2	On-study tumor assessments occur every 8 weeks (Arms 1-5),every 6 weeks (Arms 6-8) until week 48 and then every 12 weeks thereafter until radiological progression, death, withdrawal of consent or study completion up to approx. 30 months
Duration of response (DoR)	Assessment of the efficacy of each treatment arm according to RECIST 1.1. DoR: Time from date of first detection of objective response (which is subsequently confirmed) until the date of objective radiological disease progression Applicable for Part 1 and Part 2	On-study tumor assessments occur every 8 weeks (Arms 1-5), every 6 weeks (Arms 6-8) until week 48 and then every 12 weeks thereafter until radiological progression, death, withdrawal of consent or study completion up to approx. 30 months
Serum concentration of durvalumab and serum or plasma concentration of novel oncology therapies	Assessment of pharmacokinetics (PK) Applicable for Part 1 (Arms 1-8) and for Part 2 (Arm 7)	From cycle 1 day 1 until cycle 7 day 1 (Arms 1-5), from cycle 1 day 1 until cycle 8 day 1 (Arms 6-8) (each cycle is 28 days) and every 12 weeks thereafter until study completion approx. 30 months
Presence of anti-drug antibodies (ADAs) for durvalumab and applicable novel oncology therapies	Investigation of the immunogenicity of durvalumab and novel oncology therapies in all applicable treatment arms Applicable for Part 1 (Arms 1-8) and for Part 2 (Arm 7)	From cycle 1 day 1 until cycle 7 day 1 (Arms 1-5), from cycle 1 day 1 until cycle 8 day 1 (Arms 6-8) (each cycle is 28 days) and every 12 weeks thereafter until study completion approx. 30 months
Progression-free survival (PFS 6)	PFS at 6 months following date of first dose Applicable for Part 2	On-study tumor assessments occur every 8 weeks until week 48 (Arms 1-5), every 6 weeks until week 48 (Arms 6-8) and then every 12 weeks thereafter until radiological progression, death, withdrawal of consent or study completion up to approx. 30 months

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• https://breastcancerstudylocator.com/

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2018
• Primary Completion (Estimated): August 15, 2024
• Study Completion (Estimated): August 15, 2024

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): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: March 1, 2024

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: Skin Diseases; Neoplasms by Site; Breast Diseases; Neoplasms; Breast Neoplasms; Triple Negative Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Immunoconjugates; Paclitaxel; Trastuzumab; 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