A Study of Dato-DXd With or Without Durvalumab Versus Investigator’s Choice of Therapy in Patients With Stage I-III Triple-negative Breast Cancer Without Pathological Complete Response Following Neoadjuvant Therapy

Overview

Sponsor-declared trial summary

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

24 Feb 2023 → ongoing

Decision date (initial)

2024-05-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2023-505552-22-00

EudraCT number

2022-002680-30

ClinicalTrials.gov

NCT05629585

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To demonstrate superiority of Dato-DXd in combination with durvalumab relative to ICT by assessment of iDFS in participants with stage I to III TNBC with residual invasive disease at surgical resection following neoadjuvant therapy

Secondary objectives 1

1. 1. To demonstrate superiority of Dato-DXd + durvalumab relative to ICT by a) DDFS, b) OS. 2. To demonstrate superiority of Dato-DXd relative to ICT by iDFS. 3. To assess efficacy of Dato-DXd relative to ICT by a)DDFS, b) OS. 4. To assess efficacy of Dato-DXd relative to ICT by a) iDFS, b) DDFS, c) OS. 5. To assess efficacy of Dato-DXd + durvalumab relative Dato-DXd by a) iDFS, b) DDFS. 6. To assess by TTD and score levels of participant-reported a) physical function, b) QHS/QoL with Dato-DXd +/- durvalumab vs ICT. 7. To assess patient-reported fatigue Dato-DXd +/- durvalumab vs ICT. 8. To assess the a) pharmacokinetics and b) immunogenicity of Dato- Dxd. 9. To assess safety and tolerability of Dato-DXd +/- durvalumab vs ICT

Conditions and MedDRA coding

Stage I-III Triple-negative Breast Cancer with residual invasive disease after neoadjuvant systemic therapy.

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1.Participant must be ≥ 18 years at the time of screening; Male or female 2.Histologically confirmed invasive TNBC 3.Residual invasive disease in the breast and/or axillary lymph node (s) at surgical resection following neoadjuvant therapy 4.Completed at least 6 cycles of neoadjuvant therapy containing an anthracycline and/or taxane with or without platinum chemotherapy, with or without pembrolizumab. 5.No evidence of locoregional or distance relapse 6.Surgical removal of all clinically evident disease in the breast and lymph nodes 7.FFPE tumor sample from residual invasive disease at surgery 8.No adjuvant systemic therapy. Radiotherapy (if indicated) delivered before start of study treatment 9.No more than 6 weeks between completion of post-operative radiation therapy and randomization. If no post-operative radiation therapy, no more than 16 weeks between the date of breast surgery and randomization 10.Eligible for one of the therapy options listed as ICT 11.No known germline BRCA1 or BRCA2 pathogenic mutation 12.Adequate organ and bone marrow function; LVEF ≥ 50% by echocardiogram or MUGA; ECOG 0 or 1

Exclusion criteria 1

1. 1.Stage IV (metastatic) TNBC 2.History of prior invasive breast cancer or evidence of recurrent disease following preoperative therapy and surgery 3.Prior anticancer therapy with topoisomerase I ADC, TROP2-targeted therapy (e.g., Trodelvy), participated in clinical studies with T-DXd 4.Prior exposure to a PD-1/PD-L1 inhibitor other than pembrolizumab 5.Severe or uncontrolled medical conditions including systemic diseases, history of allogeneic organ transplant and active bleeding diseases, ongoing or active infection, serious chronic gastrointestinal conditions associated with diarrhea; infections; active or uncontrolled HBV or HCV uncontrolled HIV; active TB 6.Persistent toxicities caused by previous anticancer therapy, excluding alopecia, not yet improved to Grade ≤1 7.History of ILD or severe pulmonary function compromise 8.Clinically significant corneal disease 9.Any known active or prior documented autoimmune or inflammatory disorders 10.Any known active liver disease 11.Uncontrolled or significant cardiac disease 12.Grade ≥2 peripheral neuropathy of any etiology 13.History of severe hypersensitivity to either drug substances or inactive ingredients of Dato-DXd or history of hypersensitivity to PD- 1/PD-L1 inhibitors or capecitabine

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Invasive disease-free survival (iDFS), defined as time from randomization until date of first event (local, regional, contralateral or distant breast cancer recurrence, second primary non-breast invasive cancer, or death from any cause. iDFS is based on investigator assessment. Analysis includes all randomised participants, regardless of withdrawal or receipt of another anticancer therapy. Measure of interest is HR of iDFS for Dato-DXd + durvalumab vs ICT.

Secondary endpoints 12

1. 1. DDFS is defined as time from randomisation to date of the first distant recurrence, occurrence of second primary non-breast invasive cancer (other than squamous or basal cell skin cancer), or death from any cause. DDFS will be determined based on investigator assessment. The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anticancer therapy. Measure of interest will be HR of DDFS.
2. 2. DDFS for Dato-DXd vs ICT
3. 3. DDFS for Dato-DXd + durvalumab vs Dato-DXd
4. 4. Overall Survival (OS): defined as time from randomization until date of death due to any cause. The analysis will include all randomised participants, as randomised regardless of whether the participant withdraws from randomised therapy or received another anticancer therapy. Measure of interest will be the HR of OS for Dato-DXd + durvalumab vs ICT
5. 5. OS for Dato-DXd vs ICT
6. 6. iDFS for Dato-DXd vs ICT
7. 7. iDFS for Dato-DXd + durvalumab vs IC
8. 8. Clinical Outcome Assessments (PRO endpoints): Time to Deterioration (TTD) and actual scores: in physical function as measured by the PROMIS Physical Function Short Form 8c and GHS/QoL as measured by the GHS/QoL scale from the EORTC IL172. The measure of interest is the HR of TTD and physical function and GHS/QoL scores for Dato-DXd +/- durvalumab vs ICT
9. 9. Fatigue as measured by PROMIS Fatigue Short Form 7a. The measure of interest is the proportion of participants experiencing different levels of fatigue and actual scores at 3, 6, 12 months for Dato-DXd +/- durvalumab vs ICT
10. 10. Pharmacokinetics of Dato-DXd
11. 11. Immunogenicity of Dato-DXd
12. 12. Safety and tolerability

Investigational products

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

Test 2

Comparator 2

Auxiliary 2

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

Locations

8 EU/EEA countries · 89 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 73 files

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

Application history

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