A study of novel anti-cancer agents in patients with metastatic triple negative breast cancer - BEGONIA

Study identifier:D933LC00001

ClinicalTrials.gov identifier:NCT03742102

EudraCT identifier:2018-000764-29

CTIS identifier:N/A

Recruitment Complete

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

Medical condition

Triple Negative Breast Neoplasms

Phase

Phase 1/2

Healthy volunteers

Study drug

Durvalumab, Durvalumab, Durvalumab, Durvalumab, Durvalumab, Durvalumab, Capivasertib, Oleclumab, Paclitaxel, Paclitaxel, Paclitaxel, Trastuzumab deruxtecan, Datopotamab deruxtecan, Datopotamab deruxtecan

Sex

Female

Actual enrollment

240

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 21 Dec 2018

Estimated Primary Completion Date: 15 Aug 2024

Estimated Study Completion Date: 15 Aug 2024

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Apr 2023 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

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.

No locations available

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

Documents available

https://breastcancerstudylocator.com/
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Contact Backup

AZ Breast Cancer Study Navigators AZ Breast Cancer Study Navigators

+1-877-400-4656