protocolSection identificationModule nctId: NCT06298084, orgStudyIdInfo id: 2023-505925-15-00, secondaryIdInfos id: 2023/3668, type: OTHER, domain: CSET number, briefTitle: Dose-Expansion Modular Study To Explore the Safety, Tolerability, and Anti-tumor Activity of HER3- DXd Monotherapy and Combinations in Patients With Inoperable Advanced Breast Cancer (ABC) After Progression on T-DXd, acronym: ICARUSBREAST02, statusModule overallStatus: RECRUITING, startDateStruct date: 2024-03-21, primaryCompletionDateStruct date: 2027-09, completionDateStruct date: 2029-06, studyFirstPostDateStruct date: 2024-03-07, lastUpdatePostDateStruct date: 2024-03-29, sponsorCollaboratorsModule leadSponsor name: Gustave Roussy, Cancer Campus, Grand Paris, class: OTHER, collaborators name: Daiichi Sankyo, descriptionModule briefSummary: ICARUS-BREAST02 is an open-label, multicenter, phase 1b/2, platform study that aims to evaluate the safety, tolerability, and efficacy of HER3-DXd monotherapy and in combination with other anti-cancer agents in patients with ABC.The first 2 modules will evaluate: i. safety and efficacy of HER3-DXd with olaparib in patients with HER2-low and HER2-positive ABC progressed on T-DXd (Module 1) and HER3-DXd monotherapy in patients with HER2-low ABC progressed on T-DXd (Module 0).The main objective of Part 1 is to assess the safety and tolerability of HER3-DXd monotherapy and combination and to determine the recommended phase 2 dose (RP2D) of the combination containing HER3-DXd.The main objective of Part 2 is to assess the efficacy of study therapies in each module based on investigator assessment as evaluated by the objective response rate (ORR) at 6 months., conditionsModule conditions: Breast Cancer Metastatic, conditions: HER2-positive Metastatic Breast Cancer, conditions: HER2 Low Breast Carcinoma, conditions: Advanced Breast Cancer, designModule studyType: INTERVENTIONAL, phases: PHASE1, phases: PHASE2, designInfo allocation: NON_RANDOMIZED, interventionModel: SEQUENTIAL, primaryPurpose: TREATMENT, maskingInfo masking: NONE, enrollmentInfo count: 152, type: ESTIMATED, armsInterventionsModule interventions name: Patritumab deruxtecan, interventions name: Olaparib, outcomesModule primaryOutcomes measure: DLTs (dose-limiting toxicity) for part 1a and 1b, primaryOutcomes measure: Frequency of safety event for part 1a and 1b, primaryOutcomes measure: Severity of safety event for part 1a and 1b, primaryOutcomes measure: Proportion of treatment modification due to AEs for part 1a and 1b, primaryOutcomes measure: frequency of laboratory abnormalities for part 1a and 1b, primaryOutcomes measure: Severity of laboratory abnormalities for part 1a and 1b, primaryOutcomes measure: radiographic changes potentially consistent with ILD/pneumonitis or any other pulmonary signs/symptoms for part 1a and 1b, primaryOutcomes measure: ORR for part 2, primaryOutcomes measure: DOR for part 2, primaryOutcomes measure: PFS for part 2, primaryOutcomes measure: CBR for part 2, secondaryOutcomes measure: ORR for part 1, secondaryOutcomes measure: DOR for part 1, secondaryOutcomes measure: PFS for part 1, secondaryOutcomes measure: CBR for part 1, secondaryOutcomes measure: PK analysis for part 1, secondaryOutcomes measure: ADA analysis for part 1, secondaryOutcomes measure: DLTs for part 2, secondaryOutcomes measure: Frequency of safety event for part 2, secondaryOutcomes measure: Severity of safety event for part 2, secondaryOutcomes measure: proportion of treatment modification event for part 2, secondaryOutcomes measure: frequency of laboratory abnormalities for part 2, secondaryOutcomes measure: Severity of laboratory abnormalities for part 2, secondaryOutcomes measure: radiographic changes potentially consistent with ILD/pneumonitis or any other pulmonary signs/symptoms for part 2, secondaryOutcomes measure: PK analysis for part 2, secondaryOutcomes measure: ADA analysis for part 2, eligibilityModule sex: ALL, minimumAge: 18 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: Gustave Roussy Institut, status: RECRUITING, city: Villejuif, zip: 94805, country: France, contacts name: Barbara Pistilli, role: CONTACT, phone: +33 (0)1 42 11 61 62, email: barbara.pistilli@gustaveroussy.fr, contacts name: Fernanda Mosele, role: CONTACT, phone: +33 (0)1 42 11 61 43, email: Mariafernanda.MOSELE@gustaveroussy.fr, geoPoint lat: 48.7939, lon: 2.35992, hasResults: False