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Triple Negative Breast Cancer MetastaticPhase 2ATRiBRAVENCT05582538

Restoring Sensitivity To Immunotherapy In Advanced Triple Negative Breast Cancer Exploiting Ceralasertib Priming Followed By Combined Durvalumab/Nab-Paclitaxel

A Phase 2 study testing Ceralasertib, Durvalumab and Nab-paclitaxel in people with Triple Negative Breast Cancer Metastatic, run by IFOM ETS - The AIRC Institute of Molecular Oncology at 6 sites in Italy.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This study will evaluate the efficacy and safety of ceralasertib followed by durvalumab plus nab-paclitaxel in 37 patients with TNBC, whose tumor relapsed following treatment with curative intent for early disease, which must have included immunotherapy and chemotherapy as part of the radical locoregional therapy… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Triple Negative Breast Cancer Metastatic
What is being tested?
Ceralasertib, Durvalumab and Nab-paclitaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
37 participants
Where
6 sitesItaly
Study dates
15 Dec 2022to Dec 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • ATRiBRAVE trial written informed consent, prior to any study specific procedures
  • Age ≥18 years old
  • Ability to comply with the study protocol in the investigator's judgment.
  • Ability to swallow and retain oral medication
  • Availability of a formalin-fixed, paraffin-embedded block (FFPE) containing primary tumor tissue or at least 10-20 unstained tumor slides
  • Metastatic TNBC patients who have not received prior systemic cytotoxic therapy in the advanced setting and whose tumor have relapsed from treatment with curative intent for early disease, which must have included ICI and chemotherapy as part of radical locoregional therapy
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  • Documented disease progression (e.g., with biopsy sample, pathology or imaging report) since the last treatment in the early setting with curative intent (neo/adjuvant regimen)
  • Negative ER/PgR (defined as <10% of tumor cells expressing ER and PgR hormonal receptors) and HER2 status (HER2 IHC score 0, 1+ or 2+ non-amplified by in situ hybridization) must be confirmed in the most recent tumor sample (primary and/or metastatic)
  • Evaluable disease, as defined by RECIST 1.1
  • ECOG performance status 0-1 (refer to Appendix 1)
  • Patients must have a life expectancy ≥ 3 months from proposed first dose date.
  • Patients must have acceptable bone marrow, liver and renal functions measured within 28 days prior to administration of study treatment
  • Body weight > 30kg
  • Women with childbearing potential should complete a pregnancy test with negative result within 28 days of study treatment and be willing to use effective contraceptive methods from screening to 90 days after the last dose of durvalumab
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm from screening to 90 days after the last dose of durvalumab.

Who cannot join

  • Diagnosis of ataxia telangiectasia.
  • Any previous treatment with ATR inhibitors, DNA-damage repair inhibitors.
  • Patients, who have received prior anti-PD-1, anti PD-L1 or anti CTLA-4 therapy:
  • Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
  • All AEs while receiving prior immunotherapy must have completely resolved or resolved to baseline prior to screening for this study.
  • Must not have experienced a ≥ Grade 3 immune related AE or an immune related neurologic or ocular AE of any grade while receiving prior immunotherapy. NOTE: Patients with endocrine AE of ≤ Grade 2 are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic.
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  • Must not have required the use of additional immunosuppression other than corticosteroids infliximab or Cellcept for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of > 10 mg prednisone or equivalent per day.
  • Treatment with any investigational product during the last 28 days before the enrollment.
  • Patients must have had a washout period of 3 weeks for any prior cancer therapy prior to the start of study drug. The following intervals between the end of the prior treatment and first dose of study drug must be observed: ≥ 4 weeks for radiotherapy (patients who receive palliative radiation for nontarget lesions need not have a 4 week washout period and can be enrolled immediately); patients may receive a stable dose of bisphosphonates or denosumab for bone metastases, before and during the study; ≥ 4 weeks for major surgery; ≥ 7 days for minor surgical procedures; ≥ 14 days (or 5 half-lives whoever is longest) for any investigational product.
  • Current or prior use of immunosuppressive medication within 4 weeks prior to the first dose of durvalumab, with the exceptions of intranasal, topical, inhaled corticosteroids, and systemic corticosteroids ≤ 10 mg prednisone / day or equivalent.
  • Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, or other solid tumours curatively treated with no evidence of disease for ≤3 years.
  • Any gastrointestinal condition that would preclude adequate absorption of ceralasertib, including but not limited to inability to swallow oral medication, refractory nausea and vomiting, chronic gastrointestinal diseases or previous significant bowel resection, intestinal obstruction or CTCAE grade 3 or grade 4 upper GI bleeding within 4 weeks before the enrollment.
  • Active or prior documented autoimmune or inflammatory disorders (including IBD [e.g. Crohn's disease, ulcerative colitis or diverticulitis], SLE, sarcoidosis syndrome, tuberculosis, Wegener syndrome, myasthenia gravis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, history of primary immunodeficiency or HIV infection, known hepatitis B or hepatitis C infection, glomerulonephritis, nephritic syndrome, Fanconi Syndrome or renal tubular acidosis within the past 2 years prior to the start of treatment. The following are exceptions to this criterion: i) Subjects with vitiligo or alopecia; ii) hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement; iii) any chronic skin condition that does not require systemic therapy; iv) patients with coeliac disease controlled by diet alone and patients without active disease in the last 5 years may be included but only after consultation with the study physician.
  • Known active hepatitis infection, positive hepatitis C virus (HCV) antibody, hepatitis B virus (HBV) surface antigen (HBsAg) or HBV core antibody (anti-HBc), at screening. Participants with a past or resolved HBV infection (defined as the presence of anti-HBc and absence of HbsAg) are eligible. Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies) or active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice).
  • Receipt of a live, attenuated vaccine within 30 days prior to the first dose of study treatment.
  • Patients with confirmed COVID-19 infection by PCR test who have not made a full recovery
  • History of allogeneic organ transplantation.
  • Untreated central nervous system (CNS) metastatic disease or cord compression. Note: Patients with asymptomatic central nervous system (CNS) metastases are eligible, provided that all of the following criteria are met: (a) The metastases are limited to the supratentorial region or cerebellum (i.e., no metastases to midbrain, pons, medulla, or spinal cord are allowed); (b) No ongoing requirement for corticosteroids as therapy for CNS disease; (c) No stereotactic radiation within 7 days or whole-brain radiation or neurosurgical resection within 2 weeks before the start of study treatment; (d) Radiographic demonstration of interim stability (i.e., no progression) between the completion of CNS-directed therapy and the screening imaging study
  • History of leptomeningeal disease
  • Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia or vitiligo
  • Resting ECG with measurable QTcF > 470 msec on 2 or more time points within a 24-hour period or family history of long QT syndrome.
  • Patients with cardiac problem as follows: uncontrolled hypertension or hypotension (BP ≥150/95 mmHg despite medical therapy, BP <90/60 mmHg or orthostatic hypotension fall in BP >20 mmHg), Left ventricular ejection fraction <55% measured by echocardiography, Atrial fibrillation with a ventricular rate >100 bpm on ECG at rest or any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block , third degree heart block, second degree heart block), Symptomatic heart failure (NYHA grade II-IV), Prior or current cardiomyopathy, Severe valvular heart disease, Uncontrolled angina (Canadian Cardiovascular Society grade II-IV despite medical therapy), Acute coronary syndrome within 6 months prior to starting treatment.
  • Stroke or transient ischemic attack in the last 6 months prior to screening.
  • Uncontrolled symptomatic pleural effusion, pericardial effusion, or ascites.
  • Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or calcium > 12 mg/dL or corrected serum calcium > ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy.
  • Severe infection within 4 weeks prior to the first dose of study treatment (Cycle 1, Day 1), including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia.
  • Treatment with oral or IV antibiotics within 2 weeks prior to initiation of study treatment (Cycle 1, Day 1).
  • Patients receiving routine antibiotic prophylaxis (e.g., to prevent chronic obstructive pulmonary disease exacerbation, urinary tract infection or for dental extraction) are eligible.
  • As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases that places the patient at unacceptable risk of toxicity or non-compliance. Examples include, but are not limited to, diabetes type I and II, active bleeding diatheses, renal transplant, uncontrolled seizures, severe COPD, superior vena cava syndrome, extensive bilateral lung disease on High Resolution CT scan, severe Parkinson's disease, refractory nausea or vomiting, irritable bowel syndrome, chronic gastrointestinal disease, significant bowel resection, psychiatric condition, or active infection including any patient known to have tuberculosis, hepatitis B, hepatitis C and human immunodeficiency virus (HIV) or requiring systemic antibiotics, antifungals or antiviral drugs. Screening for chronic conditions is not required.
  • Concomitant use of known potent cytochrome P (CYP) 3A inhibitors (e.g., ketoconazole,itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir). The required washout period prior to starting study treatment is 2 weeks.
  • Concomitant use of known strong CYP3A inducers (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort). The required washout period prior to starting study treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
  • Receiving or having received, concomitant medications, herbal supplements, and/or foods that significantly modulate Pgp activity (washout periods of 5 half-lives).
  • Known hypersensitivity to ceralasertib, durvalumab or nab-paclitaxel or any of their excipients

Trial locations and contacts

6 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Ylenia Silvestri, PhD contact

+3902574303797

clinical.trials@ifom.eu

Smeralda Rapisarda, PhD contact

+3902574303236

clinical.trials@ifom.eu

6 sites in 1 country

Italy6 sites, 6 recruiting

  • ASST Papa Giovanni XXIII

    Bergamo, 24127

    Alessandra Chirco, MD

    Recruiting

  • Istituto Nazionale dei Tumori IRCCS

    Milan

    Filippo De Braud, MD

    Claudio Vernieri, MD

    Recruiting

  • IRCCS Istituto Nazionale Tumori "Fondazione Giovanni Pascale"

    Naples, 80131

    Michelino De Laurentiis, MD

    Recruiting

  • Azienda Ospedaliero Universitaria Maggiore della Carità

    Novara, Novara

    Alessandra Gennari, MD

    Recruiting

  • Istituto Oncologico Veneto IRCCS

    Padova

    Valentina Guarneri, MD

    Recruiting

  • Azienda U.S.L. - IRCCS di Reggio Emilia

    Reggio Emilia

    Filippo Giovanardi, MD

    Recruiting

Other trials in Italy

About this study

Official title: Restoring Sensitivity To Immunotherapy In Advanced Triple Negative Breast Cancer Exploiting Ceralasertib Priming Followed By Combined Durvalumab/Nab-Paclitaxel: The ATRiBRAVE Trial

This study will evaluate the efficacy and safety of ceralasertib followed by durvalumab plus nab-paclitaxel in 37 patients with TNBC, whose tumor relapsed following treatment with curative intent for early disease, which must have included immunotherapy and chemotherapy as part of the radical locoregional therapy (either adjuvant, neoadjuvant or both).

Read the detailed description

ATRiBRAVE is a phase II, single-arm, open-label trial conducted in 37 TNBC patients with unresectable locally advanced or metastatic TNBC whose tumor relapsed following previous curative intent treatment for early disease, which must have included ICIs and chemotherapy as part of the radical locoregional therapy (either adjuvant, neoadjuvant or both).

Enrolled patients will be treated with Ceralasertib, Durvalumab and Nab-paclitaxel. Given that the safety profile of the triple combination has not been evaluated in advanced TNBC patients so far, a safety run-in phase will be carried out using a 3+3 de-escalating schema down to -2 ceralasertib dose level. Once the definitive dose for ceralasertib is established, treatment will be continued until progression or unacceptable toxicity, which ever come first.

Tumor assessments will be performed every 8 weeks (± 1 week) for the first 12 months after treatment initiation and every 12 weeks (± 1 week) thereafter until PD per RECIST v1.1 or death, withdrawal of consent, or study termination by the Sponsor, whichever occurs first. Tumor assessments will be performed according to the pre-specified schedule regardless of treatment delays.

Blood (mandatory) and tumor (optional) samples will be collected at specific timepoints in order to conduct exploratory biomarker assessments, investigating mechanism of the study treatments within the tumor microenvironment, possible resistance mechanisms, potential predictive and prognostic markers.

Being tested
Ceralasertib, Durvalumab, Nab-paclitaxel
Keywords
immunotherapy, ATR inhibition, ceralasertib, durvalumab, nab-paclitaxel
Medical subject headings
Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CeralasertibDrug

    Also called AZD6738

    240mg orally BD (dose level 0) on days -6 to 0 prior to day 1 cycle 1 and then on days 22 to 28 of cycle 1 and every subsequent cycle

  • DurvalumabDrug

    Also called IMFINZI

    1500 mg i.v. day 1 (q28)

  • Nab-paclitaxelDrug

    Also called ABRAXANE, PAZENIR

    100mg/m2 i.v. day 1,8,15 (q28)

Study groups in NCT05582538
Study groupRoleWhat they receive
TNBC patients treated with ceralasertib, durvalumab e nab-paclitaxelExperimentalPatients will be assessed for eligibility during the 28-day screening period prior to enrollment. Enrolled patients will be treated with: * Ceralasertib at 240 mg administered orally, twice daily on Days -6 to 0 prior to Day 1 Cycle 1 and thereafter on Days 22 to 28 (priming period) of Cycle 1 and every subsequent cycle; * Durvalumab at 1500 mg administered via IV infusion on Day 1 of every 28-day cycle; Nab-paclitaxel at 100 mg/m2 administered via IV infusion on Days 1,8 and 15 of every 28- day cycle. A safety run-in phase will be carried out at the start of the present study using a 3+3 de-escalating schema down to -2 ceralasertib dose level. Nab- paclitaxel or durvalumab doses will not be de-escalated. Once the definitive dose for ceralasertib is established, treatment will be continued until progression or unacceptable toxicity, which ever come first.
Receives: Drug: Ceralasertib; Drug: Durvalumab; Drug: Nab-paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression free survival (PFS)

    ATRiBRAVE will evaluate the 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).

    Measured: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months

Secondary outcomes (6)

  1. Overall Response Rate (ORR)

    Overall Response Rate (ORR) according to RECIST v 1.1 criteria

    Measured: up to 12 months

  2. Disease Control Rate (DCR)

    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 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;

    Measured: 3 months

  3. Clinical Benefit Rate (CBR)

    CBR defined as the proportion of patients with no disease progression at 24 weeks

    Measured: 6 months

  4. Duration of Response (DoR)

    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

    Measured: up to 12 months

  5. Overall Survival (OS)

    OS defined as the number of days between the first study treatment administration and death;

    Measured: 2, 3, 5 years

  6. Number of adverse events according to CTCAE version 5.0

    Safety and tolerability

    Measured: up to 90 days from the last durvalumab administration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Oct 2022
  2. Study start15 Dec 2022
  3. Primary completionDec 2027 (estimated)
  4. Study completionDec 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
37 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05582538
Sponsor's protocol ID
IFOM-CPT008/2022/PO007
Other IDs
2022-001669-11
Acronym
ATRiBRAVE
Status last verified
Aug 2025
First submitted
5 Oct 2022
Last updated
24 Aug 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ceralasertib, Durvalumab and Nab-paclitaxel in people with Triple Negative Breast Cancer Metastatic, run by IFOM ETS - The AIRC Institute of Molecular Oncology at 6 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 24 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Ylenia Silvestri, PhD (+3902574303797, clinical.trials@ifom.eu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression free survival (PFS) (time frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05582538.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2025.

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