Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Immune System Diseases

Breast Neoplasms

Hypersensitivity

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Immunomodulating Agents

Durvalumab

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

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.

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

Ceralasertib

Nab-paclitaxel

Silvia Marsoni, MD

Ylenia Silvestri, PhD

Filippo De Braud, MD

Claudio Vernieri, MD

Alessandra Gennari, MD

Valentina Guarneri, MD

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).

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.

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

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

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).

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

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;

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

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

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Restoring Sensitivity To Immunotherapy In Advanced Triple Negative Breast Cancer Exploiting Ceralasertib Priming Followed By Combined Durvalumab/Nab-Paclitaxel	NCT05582538	Triple Negative...	Ceralasertib Durvalumab Nab-paclitaxel	18 Years -	IFOM ETS - The AIRC Institute of Molecular Oncology
Restoring Sensitivity To Immunotherapy In Advanced Triple Negative Breast Cancer Exploiting Ceralasertib Priming Followed By Combined Durvalumab/Nab-Paclitaxel	NCT05582538	Triple Negative...	Ceralasertib Durvalumab Nab-paclitaxel	18 Years -	IFOM ETS - The AIRC Institute of Molecular Oncology

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