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.
Patients must have received prior treatment with T-DXd and presented disease progression while on T-DXd treatment or within 2 months from T-DXd interruption/discontinuation for any reason, without requiring to be the last line of treatment. Patients who have received other lines of treatment after T-DXd and before study entry is capped at 10 patients for each cohort.
Patients with HER2-positive tumors must have received prior treatment with trastuzumab and taxanes. They may have received prior treatment with T-DM1 and pertuzumab.
Patients with HER2-low tumors must have been treated with taxanes. Patients with HR-positive tumors must have received ET and CDK4/6 inhibitors (patients may have received prior treatment with sacituzumab govitecan) If a patient has a tumor that was previously HER2-pos and became HER2-low, she/he will be included in cohort 2 and meet the inclusion criteria for HER2-low tumors.
Patients with germline pathogenic BRCA1/2 mutations and HER2-positive or HER2-low breast cancer are eligible to the study but must have received a prior treatment with PARP inhibitor (olaparib or talazoparib)
Patient with a breast cancer amenable for resection or radiation therapy with curative intent
Patient with any history of ILD (including pulmonary fibrosis or radiation pneumonitis), has current ILD, or is suspected to have ILD as assessed by imaging during screening
Any underlying pulmonary disorder (eg, pulmonary embolism, severe asthma, severe chronic obstructive pulmonary disease (COPD), restrictive lung disease, pleural effusion) OR
Any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement (eg, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis) OR
Sequential
Patritumab deruxtecan
Drug5.6 mg/kg every 21 days
Olaparib
Drug100 mg b.i.d PO days 8-14 every 21 days
DLTs (dose-limiting toxicity) for part 1a and 1b
DLTs
Frequency of safety event for part 1a and 1b
frequency of any AEs, TEAEs, SAEs, AESIs graded by NCI-CTCAE v5.0
Severity of safety event for part 1a and 1b
severity of any AEs, TEAEs, SAEs, AESIs graded by NCI-CTCAE v5.0
Proportion of treatment modification due to AEs for part 1a and 1b
Proportion of treatment discontinuations, interruptions, and dose reductions due to any AEs
ORR for part 1
ORR is defined as the proportion of patients who achieved a confirmed complete response (CR) or partial response (PR) assessed by investigators after 6 months of treatment initiation. The objective response will be radiologically assessed every 6 weeks during the first year than every 12 weeks thereafter using RECIST v1.1.
DOR for part 1
DOR is defined as the time from the date of the first documentation of confirmed response (CR or PR) to the date of the first documentation of progression (PD) or death due to any cause, whichever occurs first.Duration of response will be measured for responding patients (CR or PR) only
PFS for part 1
PFS is defined as the time from date of first dose until the date of the first objective documentation of disease progression or death from any cause, whichever occurs first. For patients without documented radiological progression, PFS will be censored at the date of last adequate radiological assessment without progression.
CBR for part 1
CBR is defined as the presence of at least a confirmed PR or CR, or a stable disease (SD) ≥6 months
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Gustave Roussy, Cancer Campus, Grand Paris
Lead sponsor
Daiichi Sankyo
Collaborator
