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

NCT ID: NCT03742102

Last Updated: 2025-10-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

243 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-12-21

Study Completion Date

2027-02-26

Brief Summary

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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

Detailed Description

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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

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Triple Negative Breast Neoplasms

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 1

durvalumab + paclitaxel

Group Type EXPERIMENTAL

Durvalumab

Intervention Type DRUG

Durvalumab iv Every 4 weeks (q4w) or 3 weeks (q3w) Arm 6, 7 and 8

Paclitaxel

Intervention Type DRUG

Paclitaxel iv 4-week cycles: 3 weeks once weekly (q1w) and 1 week off

Arm 2

durvalumab + paclitaxel + capivasertib

Group Type EXPERIMENTAL

Durvalumab

Intervention Type DRUG

Durvalumab iv Every 4 weeks (q4w) or 3 weeks (q3w) Arm 6, 7 and 8

Capivasertib

Intervention Type DRUG

Capivasertib oral bid 4-week cycles; 3 weeks on (dosing on days 2,3,4 and 5) and 1 week off

Paclitaxel

Intervention Type DRUG

Paclitaxel iv 4-week cycles: 3 weeks once weekly (q1w) and 1 week off

Arm 5

durvalumab + paclitaxel + oleclumab

Group Type EXPERIMENTAL

Durvalumab

Intervention Type DRUG

Durvalumab iv Every 4 weeks (q4w) or 3 weeks (q3w) Arm 6, 7 and 8

Oleclumab

Intervention Type DRUG

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

Paclitaxel

Intervention Type DRUG

Paclitaxel iv 4-week cycles: 3 weeks once weekly (q1w) and 1 week off

Arm 6

durvalumab + trastuzumab deruxtecan

Group Type EXPERIMENTAL

Durvalumab

Intervention Type DRUG

Durvalumab iv Every 4 weeks (q4w) or 3 weeks (q3w) Arm 6, 7 and 8

Trastuzumab deruxtecan

Intervention Type DRUG

Trastuzumab deruxtecan iv 3-week cycles (once weekly) q3w

Arm 7

durvalumab + datopotamab deruxtecan

Group Type EXPERIMENTAL

Durvalumab

Intervention Type DRUG

Durvalumab iv Every 4 weeks (q4w) or 3 weeks (q3w) Arm 6, 7 and 8

Datopotamab deruxtecan

Intervention Type DRUG

Datopotamab deruxtecan iv 3-week cycles (once weekly) q3w

Arm 8

durvalumab + datopotomab deruxtecan (patients with PD-L1 positive status)

Group Type EXPERIMENTAL

Durvalumab

Intervention Type DRUG

Durvalumab iv Every 4 weeks (q4w) or 3 weeks (q3w) Arm 6, 7 and 8

Datopotamab deruxtecan

Intervention Type DRUG

Datopotamab deruxtecan iv 3-week cycles (once weekly) q3w

Interventions

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Durvalumab

Durvalumab iv Every 4 weeks (q4w) or 3 weeks (q3w) Arm 6, 7 and 8

Intervention Type DRUG

Capivasertib

Capivasertib oral bid 4-week cycles; 3 weeks on (dosing on days 2,3,4 and 5) and 1 week off

Intervention Type 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

Intervention Type DRUG

Paclitaxel

Paclitaxel iv 4-week cycles: 3 weeks once weekly (q1w) and 1 week off

Intervention Type DRUG

Trastuzumab deruxtecan

Trastuzumab deruxtecan iv 3-week cycles (once weekly) q3w

Intervention Type DRUG

Datopotamab deruxtecan

Datopotamab deruxtecan iv 3-week cycles (once weekly) q3w

Intervention Type DRUG

Other Intervention Names

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MEDI4736 AZD5363 MEDI9447 DS-8201a Dato-DXd; DS-1062a

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

130 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Peter Schmid, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Barts Cancer Institute

Locations

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Research Site

Tucson, Arizona, United States

Site Status

Research Site

Columbia, Maryland, United States

Site Status

Research Site

Boston, Massachusetts, United States

Site Status

Research Site

Boston, Massachusetts, United States

Site Status

Research Site

Grand Rapids, Michigan, United States

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Research Site

St Louis, Missouri, United States

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Dallas, Texas, United States

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Research Site

Williamsburg, Virginia, United States

Site Status

Research Site

Kelowna, British Columbia, Canada

Site Status

Research Site

London, Ontario, Canada

Site Status

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Greenfield Park, Quebec, Canada

Site Status

Research Site

Montreal, Quebec, Canada

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Gdansk, , Poland

Site Status

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Krakow, , Poland

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Lublin, , Poland

Site Status

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Opole, , Poland

Site Status

Research Site

Rzeszów, , Poland

Site Status

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Warsaw, , Poland

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Warsaw, , Poland

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Kaohsiung City, , Taiwan

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Taichung, , Taiwan

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Tainan City, , Taiwan

Site Status

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taoyuan District, , Taiwan

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Cambridge, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Oxford, , United Kingdom

Site Status

Countries

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United States Canada Poland South Korea Taiwan United Kingdom

Related Links

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https://www.breastcancerstudylocator.com/trial/listing/188918

Breast Cancer Study Locator details (for US)

Other Identifiers

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2018-000764-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D933LC00001

Identifier Type: -

Identifier Source: org_study_id

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