A Phase IB/II Study to determine efficacy and safety of Durvalumab + Paclitaxel and Durvalumab in Combination with Novel Oncology Therapies with or without Paclitaxel for First-line Metastatic Triple Negative Breast Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

11 Jul 2019 → ongoing

Decision date (initial)

2024-08-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AstraZeneca

External identifiers

EU CT number

2024-511646-40-00

EudraCT number

2018-000764-29

ClinicalTrials.gov

NCT03742102

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis, Safety, Prophylaxis

Part 1: To assess the safety and tolerability profile of durvalumab + novel oncology therapies with or without paclitaxel and durvalumab + paclitaxel.
Part 2: To assess the efficacy of durvalumab + novel oncology therapies with or without paclitaxel in terms of ORR.

Secondary objectives 5

1. Part 1: To assess the efficacy of durvalumab + novel oncology therapies with or without paclitaxel and durvalumab + paclitaxel in terms of ORR, PFS, DoR, and OS
2. Part 1: To assess the PK of durvalumab and novel oncology therapies in all treatment arms
3. Part 1:To investigate the immunogenicity of durvalumab and novel oncology therapies in all applicable treatment arms
4. Part 2: To assess the efficacy of durvalumab + novel oncology therapies with or without paclitaxel in terms of PFS, DoR, PFS6 and OS
5. Part 2: To assess the safety and tolerability profile of durvalumab + novel oncology therapies with or without paclitaxel

Conditions and MedDRA coding

First-line (1L) Stage IV Triple Negative Breast Cancer (TNBC) - the subtype of breast cancer characterized by a lack of tumor expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2.

Study design 4 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

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
7. 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
8. Patients enrolled in Arm 8 (durvalumab + Dato-DXd): Must have PD-L1 positive tumor as determined by an IHC based assay

Exclusion criteria 15

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%
9. 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)
10. Patients enrolled in Arm 2 only: Diagnosis of diabetes mellitus Type I or diabetes mellitus Type II requiring insulin treatment
11. Patients enrolled in Arm 5 only: History of venous thromboembolism in the past 3 months
12. Patients enrolled in Arm 7 and Arm 8 only: Clinically significant corneal disease in the opinion of the Investigator.
13. Patients enrolled in Arm 6, 7 and 8 only: History of or active interstitial lung disease/pneumonitis
14. Patients enrolled in Arm 6, 7 and 8 only: Use of chloroquine or hydroxychloroquine in <14 days prior to Day 1 of DS-8201a (Arm 6) or Dato-DXd (Arm 7 and Arm 8) treatment
15. Patients enrolled in Arm 6 only: Previously been diagnosed as HER2+ or received HER2-targeted therapy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Part 1: AEs, exposure, physical examinations, laboratory findings, and vital signs
2. 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).

Secondary endpoints 11

1. Part 1: 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)
2. Part 1: Endpoints based on Investigator assessment according to RECIST 1.1: PFS (progression-free survival): Time from date of first dose until the date of objective radiological disease progression using RECIST 1.1 or death (by any cause in the absence of progression
3. Part 1: Endpoints based on Investigator assessment according to RECIST 1.1: DoR (duration of response): Time from date of first detection of objective response (which is subsequently confirmed) until the date of objective radiological disease progression
4. Part 1: Endpoints based on Investigator assessment according to RECIST 1.1: OS (overall survival): Time from date of first dose until the date of death by any cause
5. Part 1: Serum concentration of durvalumab and serum or plasma concentration of novel oncology therapies
6. Part 1: Presence of ADAs for durvalumab and applicable novel oncology therapies
7. Part 2: Endpoints based on Investigator assessment according to RECIST 1.1: PFS (progression-free survival): Time from date of first dose until the date of objective radiological disease progression using RECIST 1.1 or death (by any cause in the absence of progression)
8. Part 2: Endpoints based on Investigator assessment according to RECIST 1.1: DoR (duration of response): Time from date of first detection of objective response (which is subsequently confirmed) until the date of objective radiological disease progression
9. Part 2: Endpoints based on Investigator assessment according to RECIST 1.1: PFS6: PFS at 6 months following date of first dose
10. Part 2: Endpoints based on Investigator assessment according to RECIST 1.1: OS (overall survival): Time from date of first dose until the date of death by any cause
11. Part 2: AEs, exposure, physical examinations, laboratory findings, and vital signs

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Third parties 1

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications