Overview
Sponsor-declared trial summary
Phase
Human pharmacology (Phase I) - Other
Status
Ended
Participants planned
192
Countries
1
Sites
1
Metastatic Breast Cancer
This study is modular in design allowing assessment of the safety, tolerability, PK and preliminary anti-tumour activity of T-DXd in combination with other therapies. Combination-treatment modules will have 2 parts: a dose-finding phase (Part 1), and a dose expansion phase (Part 2); the Part 2 dose-expansion phase will…
Key facts
- Sponsor
- Astrazeneca AB
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 11 Mar 2022 → 12 Mar 2026
- Decision date (initial)
- 2024-07-24
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
External identifiers
- EU CT number
- 2023-505690-33-00
- EudraCT number
- 2020-002797-27
- ClinicalTrials.gov
- NCT04556773
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Pharmacogenetic, Pharmacodynamic, Pharmacokinetic, Therapy, Efficacy, Pharmacogenomic
This study is modular in design allowing assessment of the safety, tolerability, PK and preliminary anti-tumour activity of T-DXd in combination with other therapies. Combination-treatment modules will
have 2 parts: a dose-finding phase (Part 1), and a dose expansion phase (Part 2); the Part 2 dose-expansion phase will use the RP2D determined in Part 1.
The target population of interest in this study is patients with HER2-low (IHC 1+ or IHC 2+/ISH -) (as per ASCO/CAP 2018 guidelines) advanced/MBC. Part 1 of each module will enroll patients with locally confirmed HER2-low advanced/MBC in second-line or later (≥ 2L) settings.
Part 2 of each module will enroll patients with HER2-low MBC who have either not received prior treatment, or received only 1 prior treatment for advanced/metastatic disease.
Part 1: To assess the safety and tolerability, and determine RP2D for the T-DXd combinations Part 2: To assess the safety and tolerability of T-DXd combinations
Part 2: To assess the safety and tolerability of T-DXd combinations
Secondary objectives 5
- Part 2: To assess anti-tumour activity of novel T-DXd combinations at the RP2D
- Part 1 and Part 2: To assess the PK of T-DXd, total anti-HER2 antibody and MAAA-1181a in serum
- Part 1 and Part 2: To assess the PK of durvalumab
- Part 1 and Part 2: To investigate the immunogenicity of T-DXd
- Part 1 and Part 2: To investigate the immunogenicity of durvalumab
Conditions and MedDRA coding
Metastatic Breast Cancer
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | SOC | 10029104 | Neoplasms benign malignant and unspecified (incl cysts and polyps) | 2 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- Patients must be at least 18 years of age
- Male or female patients who have pathologically documented breast cancer that: a)Has a history of HER2-low expression, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) with a validated assay b)Is documented as HR+ (either ER and/or PgR positive [ER or PgR ≥ 1%]) or ER and PgR negative (ER and PgR <1%) per ASCO/CAP guidelines in the metastatic setting
- Patient must have adequate tumor sample for biomarker assessment
- ECOG Performance Status of 0 or 1
- For patients with HR+ disease: Part 1: At least 1 prior treatment line of ET with or without a targeted therapy (such as CDK4/6, mTOR or PI3-K inhibitors), and at least 1 prior line of chemotherapy for MBC are required. Part 2: Only 1 prior treatment line of ET with or without a targeted therapy (such as CDK4/6, mTOR or PI3-K inhibitors) for MBC is allowed. No prior chemotherapy in the metastatic setting is allowed. Note there are no patients with HR+ disease in Part 2 of Modules 2 and 3.
- For patients with HR- disease: Part 1: At least 1 prior line of chemotherapy for MBC is required. Note there are no patients with HR- disease in Part 1 of Modules 4 and 5. Part 2: For Module 2, no prior lines of therapy for MBC are allowed, and for Modules 1 and 3, only 1 prior line of chemotherapy for MBC is allowed. Note there are no patients with HR- disease in Part 2 of Modules 4 and 5.
Exclusion criteria 9
- Uncontrolled intercurrent illness
- Uncontrolled or significant cardiovascular disease
- History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
- Lung-specific intercurrent clinically significant illnesses
- Has spinal cord compression or clinically active central nervous system metastases
- Active primary immunodeficiency
- Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
- Prior treatment with ADC that comprises of an exatecan derivative that is a topoisomerase I inhibitor
- Combination partner as the most recent anti-cancer therapy for MBC prior to commencing study treatment
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 2
- Part 1: AEs, SAEs, DLTs, laboratory findings
- Part 2: AEs, SAEs, laboratory findings
Secondary endpoints 7
- Part 2: ORR defined as the proportion of patients who have a confirmed CR or PR, as determined by the investigator at local site per RECIST 1.1
- Part 2: PFS defined as time from the date of first dose until the date of progression as determined by the investigator at local site per RECIST 1.1, or death due to any cause
- Part 2: DoR defined as time from the date of first documented response (which is subsequently confirmed) until the date of documented progression or death in the absence of disease progression
- Part 2: OS defined as time from the date of first dose until the date of death by any cause
- Serum concentration of T-DXd, total anti-HER2 antibody and MAAA- 1181a
- Serum concentration of durvalumab
- Immunogenicity of T-DXd and durvalumab
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 9
SUB09583MIG · Substance
- Active substance
- Paclitaxel
- Pharmaceutical form
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 999999 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
TRUQAP 160 mg film-coated tablets
PRD11429951 · Product
- Active substance
- Capivasertib
- Substance synonyms
- 4-AMINO-N-((1S)-1-(4-CHLOROPHENYL)-3-HYDROXYPROPYL)-1- (1H-PYRROLO(2,3-D)PYRIMIDIN-4-YL)PIPERIDINE-4-CARBOXAMIDE, AZD-5363, AZD5363
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 999999 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01EX27 — -
- Marketing authorisation
- EU/1/24/1820/001
- MA holder
- ASTRAZENECA AB
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- The clinical tablets are plain on both sides and packed in bottles, whereas the commercial tablets are debossed and packed in blister. Assigned shelf life and sites for packaging and QP release are also different for the clinical versus the commercial product.
TRUQAP 200 mg film-coated tablets
PRD11429980 · Product
- Active substance
- Capivasertib
- Substance synonyms
- 4-AMINO-N-((1S)-1-(4-CHLOROPHENYL)-3-HYDROXYPROPYL)-1- (1H-PYRROLO(2,3-D)PYRIMIDIN-4-YL)PIPERIDINE-4-CARBOXAMIDE, AZD-5363, AZD5363
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 999999 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01EX27 — -
- Marketing authorisation
- EU/1/24/1820/002
- MA holder
- ASTRAZENECA AB
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- The clinical tablets are plain on both sides and packed in bottles, whereas the commercial tablets are debossed and packed in blister. Assigned shelf life and sites for packaging and QP release are also different for the clinical versus the commercial product.
Arimidex® 1 mg film-coated tablets
PRD410197 · Product
- Active substance
- Anastrozole
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 999999 Month(s)
- Authorisation status
- Authorised
- ATC code
- L02BG03 — ANASTROZOLE
- Marketing authorisation
- PL 17901/0002
- MA holder
- ASTRAZENECA UK LIMITED
- MA country
- XI
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Product is blinded with no markings on the tablet. A different manufacturing site is used for clinical trial supply. A different drug product container closure is used (HDPE bottles) and given a 60 month shelf life.
IMFINZI 50 mg/mL concentrate for solution for infusion.
PRD6651398 · Product
- Active substance
- Durvalumab
- Substance synonyms
- MEDI4736
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 999999 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01XC28 — -
- Marketing authorisation
- EU/1/18/1322/001
- MA holder
- ASTRAZENECA AB
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Capecitabine Accord 150 mg film-coated tablets
PRD3436582 · Product
- Active substance
- Capecitabine
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 999999 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01BC06 — CAPECITABINE
- Marketing authorisation
- EU/1/12/762/004
- MA holder
- ACCORD HEALTHCARE S.L.U.
- MA country
- Liechtenstein
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Capecitabine Accord 500 mg film-coated tablets
PRD1614134 · Product
- Active substance
- Capecitabine
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 999999 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01BC06 — CAPECITABINE
- Marketing authorisation
- EU/1/12/762/025
- MA holder
- ACCORD HEALTHCARE S.L.U.
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD5308994 · Product
- Active substance
- Trastuzumab Deruxtecan
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 999999 Month(s)
- Authorisation status
- Not Authorised
- MA holder
- DAIICHI SANKYO, INC.
- Paediatric formulation
- No
- Orphan designation
- No
Faslodex 250 mg solution for injection.
PRD3545736 · Product
- Active substance
- Fulvestrant
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAMUSCULAR USE
- Max daily dose
- 00 mg/ml milligram(s)/millilitre
- Max total dose
- 00 mg/ml milligram(s)/millilitre
- Max treatment duration
- 999999 Month(s)
- Authorisation status
- Authorised
- ATC code
- L02BA03 — FULVESTRANT
- Marketing authorisation
- EU/1/03/269/002
- MA holder
- ASTRAZENECA AB
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- No Branding on syringe barrel.
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Astrazeneca AB
- Sponsor organisation
- Astrazeneca AB
- Address
- Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674
- 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
| Organisation | City, country | Duties |
|---|---|---|
| Parexel International (IRL) Limited ORG-100022780
|
Dublin 2, Ireland | On site monitoring, Code 12, Other, Code 5 |
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Belgium | Ended | 12 | 1 |
| Rest of world
Brazil, Russian Federation, United States, Taiwan, Korea, Republic of, Canada
|
— | 180 | — |
Investigational sites
Clinique Saint-Pierre
Oncologie, Avenue Reine Fabiola 9, 1340, Ottignies-Louvain-La-Neuve
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Belgium | 2022-03-11 | 2026-03-12 | 2022-03-15 | 2023-01-13 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 30 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol Main English D967JC00002 Public | 3.0 |
| Protocol (for publication) | D1_Protocol Main TMG Durvalumab English D967JC00002 Public | NA |
| Recruitment arrangements (for publication) | K1_EU CTR Recruitment Arrangements Transition Placeholder D967JC00002 | NA |
| Subject information and informed consent form (for publication) | L1_BEL Country ICF Main MODULE 1 Dutch D967JC00002 Public | 7.0 |
| Subject information and informed consent form (for publication) | L1_BEL Country ICF Main MODULE 1 English D967JC00002 Public | 7.0 |
| Subject information and informed consent form (for publication) | L1_BEL Country ICF Main MODULE 1 French D967JC00002 Public | 7.0 |
| Subject information and informed consent form (for publication) | L1_BEL Country ICF Main MODULE 2 Dutch D967JC00002 Public | 6.0 |
| Subject information and informed consent form (for publication) | L1_BEL Country ICF Main MODULE 2 English D967JC00002 Public | 6.0 |
| Subject information and informed consent form (for publication) | L1_BEL Country ICF Main MODULE 2 French D967JC00002 Public | 6.0 |
| Subject information and informed consent form (for publication) | L1_BEL Country ICF Main MODULE 3 Dutch D967JC00002 Public | 8.0 |
| Subject information and informed consent form (for publication) | L1_BEL Country ICF Main MODULE 3 English D967JC00002 Public | 8.0 |
| Subject information and informed consent form (for publication) | L1_BEL Country ICF Main MODULE 3 French D967JC00002 Public | 8.0 |
| Subject information and informed consent form (for publication) | L1_BEL Country ICF Main MODULE 4 Dutch D967JC00002 Public | 5.0 |
| Subject information and informed consent form (for publication) | L1_BEL Country ICF Main MODULE 4 English D967JC00002 Public | 5.0 |
| Subject information and informed consent form (for publication) | L1_BEL Country ICF Main MODULE 4 French D967JC00002 Public | 5.0 |
| Subject information and informed consent form (for publication) | L1_BEL Country ICF Main MODULE 5 Dutch D967JC00002 Public | 7.0 |
| Subject information and informed consent form (for publication) | L1_BEL Country ICF Main MODULE 5 English D967JC00002 Public | 7.0 |
| Subject information and informed consent form (for publication) | L1_BEL Country ICF Main MODULE 5 French D967JC00002 Public | 7.0 |
| Subject information and informed consent form (for publication) | L1_BEL Country ICF Pre-screening Dutch D967JC00002 Public | 2.0 |
| Subject information and informed consent form (for publication) | L1_BEL Country ICF Pre-screening English D967JC00002 Public | 2.0 |
| Subject information and informed consent form (for publication) | L1_BEL Country ICF Pre-screening French D967JC00002 Public | 2.0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Arimidex D967JC00002 Public | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Bendatax Paclitaxel D967JC00002 Public | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Capecitabin cell pharm D967JC00002 Public | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Capecitabin eg labo D967JC00002 Public | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Faslodex D967JC00002 Public | NA |
| Synopsis of the protocol (for publication) | D1_BEL Lay Protocol Synopsis Main Dutch D967JC00002 Public | 1.0 |
| Synopsis of the protocol (for publication) | D1_BEL Lay Protocol Synopsis Main French D967JC00002 Public | 1.0 |
| Synopsis of the protocol (for publication) | D1_BEL Lay Protocol Synopsis Main German D967JC00002 Public | 1.0 |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Synopsis Main English D967JC00002 Public | 1.0 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-07-15 | Belgium | Acceptable with conditions 2024-07-23
|
2024-07-24 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-05-05 | Belgium | Acceptable 2025-06-18
|
2025-06-23 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-12-22 | Belgium | Acceptable 2026-01-21
|
2026-01-21 |