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

NCT05582538 | Recruiting Phase 2

• 2 other identifiers: IFOM-CPT008/2022/PO0072022-001669-11
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 6

Brief 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 (either adjuvant, neoadjuvant or both).

Conditions

Triple Negative Breast Cancer Metastatic

Keywords

immunotherapy; ATR inhibition; ceralasertib; durvalumab; nab-paclitaxel

Outcome Measures

Primary Outcomes (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).

  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)

• Overall Response Rate (ORR)

  up to 12 months

• Disease Control Rate (DCR)

  3 months

• Clinical Benefit Rate (CBR)

  6 months

• Duration of Response (DoR)

  up to 12 months

• Overall Survival (OS)

  2, 3, 5 years

Study Arms (1)

TNBC patients treated with ceralasertib, durvalumab e nab-paclitaxel

EXPERIMENTAL

Patients 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.

Drug: Ceralasertib; Drug: Durvalumab; Drug: Nab-paclitaxel

Interventions

Ceralasertib DRUG

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

Also known as: AZD6738

TNBC patients treated with ceralasertib, durvalumab e nab-paclitaxel

Durvalumab DRUG

1500 mg i.v. day 1 (q28)

Also known as: IMFINZI

TNBC patients treated with ceralasertib, durvalumab e nab-paclitaxel

Nab-paclitaxel DRUG

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

Also known as: ABRAXANE, PAZENIR

TNBC patients treated with ceralasertib, durvalumab e nab-paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• IFOM ETS - The AIRC Institute of Molecular Oncology: lead
• AstraZeneca: collaborator

Study Sites (6)

Azienda Ospedaliero Universitaria Maggiore della Carità

Novara, Novara, Italy

RECRUITING

ASST Papa Giovanni XXIII

Bergamo, 24127, Italy

RECRUITING

Istituto Nazionale dei Tumori IRCCS

Milan, Italy

RECRUITING

IRCCS Istituto Nazionale Tumori "Fondazione Giovanni Pascale"

Napoli, 80131, Italy

RECRUITING

Istituto Oncologico Veneto IRCCS

Padua, Italy

RECRUITING

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

Reggio Emilia, Italy

RECRUITING

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

ceralasertib; durvalumab; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Silvia Marsoni, MD

  IFOM ETS - The AIRC Institute of Molecular Oncology

  STUDY CHAIR

Central Study Contacts

Ylenia Silvestri, PhD

CONTACT

+3902574303797; clinical.trials@ifom.eu

Smeralda Rapisarda, PhD

CONTACT

+3902574303236; clinical.trials@ifom.eu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2022
• First Posted: October 17, 2022
• Study Start: December 15, 2022
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2029
• Last Updated: August 24, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (6)