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

NCT03742102 | Active Not Recruiting Phase 1 Results FDA Drug

• 2 other identifiers: D933LC000012018-000764-29
• Study Type: interventional
• Target: 243
• Locations: 6 countries
• Sites: 32

Brief 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

Conditions

Triple Negative Breast Neoplasms

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Objective Response Rate (ORR)

  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)

  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)

  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)

  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)

  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)

Study Arms (6)

Arm 1

EXPERIMENTAL

durvalumab + paclitaxel

Drug: Durvalumab; Drug: Paclitaxel

Arm 2

EXPERIMENTAL

durvalumab + paclitaxel + capivasertib

Drug: Durvalumab; Drug: Capivasertib; Drug: Paclitaxel

Arm 5

EXPERIMENTAL

durvalumab + paclitaxel + oleclumab

Drug: Durvalumab; Drug: Oleclumab; Drug: Paclitaxel

Arm 6

EXPERIMENTAL

durvalumab + trastuzumab deruxtecan

Drug: Durvalumab; Drug: Trastuzumab deruxtecan

Arm 7

EXPERIMENTAL

durvalumab + datopotamab deruxtecan

Drug: Durvalumab; Drug: Datopotamab deruxtecan

Arm 8

EXPERIMENTAL

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

Drug: Durvalumab; Drug: Datopotamab deruxtecan

Interventions

Durvalumab DRUG

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

Also known as: MEDI4736

Arm 1; Arm 2; Arm 5; Arm 6; Arm 7; Arm 8

Capivasertib DRUG

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

Also known as: AZD5363

Arm 2

Oleclumab 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

Also known as: MEDI9447

Arm 5

Paclitaxel DRUG

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

Arm 1; Arm 2; Arm 5

Trastuzumab deruxtecan DRUG

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

Also known as: DS-8201a

Arm 6

Datopotamab deruxtecan DRUG

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

Also known as: Dato-DXd; DS-1062a

Arm 7; Arm 8

Eligibility Criteria

• Age: 18 Years - 130 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (32)

Research Site

Tucson, Arizona, 85715, United States

Location

Research Site

Columbia, Maryland, 21044, United States

Location

Research Site

Boston, Massachusetts, 02114, United States

Location

Research Site

Boston, Massachusetts, 02215, United States

Location

Research Site

Grand Rapids, Michigan, 49503, United States

Location

Research Site

St Louis, Missouri, 63110, United States

Location

Research Site

Dallas, Texas, 75246, United States

Location

Research Site

Williamsburg, Virginia, 23188, United States

Location

Research Site

Kelowna, British Columbia, V1Y 5L3, Canada

Location

Research Site

London, Ontario, N6A 4L6, Canada

Location

Research Site

Greenfield Park, Quebec, J4V 2H1, Canada

Location

Research Site

Montreal, Quebec, H4A 3J1, Canada

Location

Research Site

Gdansk, 80-952, Poland

Location

Research Site

Krakow, 31-501, Poland

Location

Research Site

Lublin, 20-090, Poland

Location

Research Site

Opole, 45-060, Poland

Location

Research Site

Rzeszów, 35-021, Poland

Location

Research Site

Warsaw, 02-781, Poland

Location

Research Site

Warsaw, 04-141, Poland

Location

Research Site

Seoul, 03080, South Korea

Location

Research Site

Seoul, 05505, South Korea

Location

Research Site

Seoul, 06351, South Korea

Location

Research Site

Kaohsiung City, 80756, Taiwan

Location

Research Site

Taichung, 40447, Taiwan

Location

Research Site

Tainan, 70403, Taiwan

Location

Research Site

Taipei, 10002, Taiwan

Location

Research Site

Taipei, 112, Taiwan

Location

Research Site

Taoyuan District, 333, Taiwan

Location

Research Site

Cambridge, CB2 0QQ, United Kingdom

Location

Research Site

London, EC1M 6BQ, United Kingdom

Location

Research Site

Manchester, M20 4BX, United Kingdom

Location

Research Site

Oxford, OX3 7LE, United Kingdom

Location

Related Links

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

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

durvalumab; capivasertib; Paclitaxel; trastuzumab deruxtecan

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Limitations and Caveats

Open-label study with a small patient cohort, not designed for cross-arm efficacy comparison. Efficacy judged by investigator assessment with no BICR.

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca Clinical Study Information Center

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• Peter Schmid, MD, PhD

  Barts Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 25, 2018
• First Posted: November 15, 2018
• Study Start: December 21, 2018
• Primary Completion: November 29, 2024
• Study Completion (Estimated): February 26, 2027
• Last Updated: April 24, 2026
• Results First Posted: February 2, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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.
• 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.

Locations

KR (3); CA (4); TW (6); US (8); GB (4); PL (7)