Restoring Sensitivity to Immunotherapy in Advanced Triple Negative Breast Cancer Exploiting Ceralasertib Priming Followed by Combined Durvalumab/Nab-Paclitaxel: the ATRiBRAVE Trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

IFOM Istituto Fondazione Di Oncologia Molecolare Ets In Breve Ifom Ets

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

15 Dec 2022 → ongoing

Decision date (initial)

2024-08-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AstraZeneca

External identifiers

EU CT number

2024-513721-23-00

EudraCT number

2022-001669-11

ClinicalTrials.gov

NCT05582538

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Evaluation of efficacy of ceralasertib followed by durvalumab plus Nab-paclitaxel in patients with TNBC, whose tumor relapsed following treatment with curative intent for early disease, which must have included ICIs and chemotherapy as part of the radical locoregional therapy (either adjuvant, neoadjuvant or both).

Secondary objectives 1

1. Evaluate the efficacy and safety of the study treatments.

Conditions and MedDRA coding

ADVANCED TRIPLE NEGATIVE BREAST CANCER

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Metastatic TNBC patients, chemotherapy naïve therapy for metastatic treatment and whose tumor have relapsed from treatment with curative intent for early disease, which must include ICI and chemotherapy as part of radical locoregional therapy
2. Documented disease progression (e.g., with biopsy sample, pathology or imaging report) since the last treatment in early setting with curative intent (neo/adjuvant regimen)
3. ATRiBRAVE trial written informed consent
4. Age =18 years old
5. Ability to comply with the study protocol in the investigator’s judgment, including ability to swallow and retain oral medication
6. Availability of a formalin-fixed, paraffin-embedded block (FFPE) containing primary tumor tissue or at least 10-20 unstained tumor slides
7. Negative ER/PgR and HER2 status, confirmed in the most recent tumor sample (primary and/or metastatic)
8. Evaluable disease as defined by RECIST 1.1
9. ECOG performance status 0-1
10. Acceptable organ functions measured within 28 days prior to trial
11. Negative pregnancy test and willingness to use effective contraceptive methods from screening to 90 days from the last dose of durvalumab

Exclusion criteria 10

1. Diagnosis of ataxia telangiectasia
2. Any previous treatment with ATR inhibitors, or DNA-damage repair inhibitors
3. An adequate washout period prior to the start of study for any anticancer therapy
4. Second primary cancer, except: non-melanoma skin cancer, or solid tumours curatively treated with no evidence of disease for =3 years
5. Active or prior documented autoimmune or inflammatory disorders
6. Patients with confirmed COVID-19 infection by PCR test who have not made a full recovery
7. Leptomeningeal disease or symptomatic untreated CNS metastatic disease or cord compression. Asymptomatic metastases are conditionally eligible
8. Any unresolved toxicity NCI CTCAE Grade =2 from previous anticancer therapy with the exception of alopecia and vitiligo
9. Any evidence of severe or uncontrolled organ or systemic disease
10. Any other clinical condition that may render the patient at high risk from treatment complications

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression free survival (PFS), defined as the number of days between the first study treatment administration to the date of first documented disease progression, relapse or death from any cause.

Secondary endpoints 6

1. Overall Response Rate (ORR) according to RECIST v 1.1 criteria
2. Disease Control Rate (DCR) defined as the percentage of subjects whose disease shrinks or remains stable at 12 weeks. DCR is the sum of the complete response (CR), partial response (PR) and stable disease (SD) rates
3. Clinical Benefit Rate (CBR) defined as the proportion of patients with no disease progression at 24 weeks
4. Duration of Response (DoR) defined as the time from the date of first documented confirmed response until date of documented progression per RECIST v1.1 or death due to any cause
5. Overall Survival (OS) defined as the number of days between the first study treatment administration and death
6. Occurrence of Adverse Events (AEs), including treatment-related AEs and AEs of special interest

Investigational products

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

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

IFOM Istituto Fondazione Di Oncologia Molecolare Ets In Breve Ifom Ets

Sponsor organisation

IFOM Istituto Fondazione Di Oncologia Molecolare Ets In Breve Ifom Ets

Address

Via Adamello 16

City

Milan

Postcode

20139

Country

Italy

Scientific contact point

Organisation

IFOM Istituto Fondazione Di Oncologia Molecolare Ets In Breve Ifom Ets

Contact name

Silvia Marsoni

Public contact point

Organisation

IFOM Istituto Fondazione Di Oncologia Molecolare Ets In Breve Ifom Ets

Contact name

Silvia Marsoni

Third parties 4

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 12 files

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

Application history

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