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

Sponsor
Gustave Roussy, Cancer Campus, Grand Paris
Study ID
NCT06298084
Phase
PHASE1/PHASE2
Status
Recruiting
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Conditions

  • Advanced Breast Cancer
  • Breast Cancer Metastatic
  • HER2 Low Breast Carcinoma
  • HER2-positive Metastatic Breast Cancer

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Patritumab deruxtecan — DRUG
    5.6 mg/kg every 21 days
  • Olaparib — DRUG
    100 mg b.i.d PO days 8-14 every 21 days

Study Details

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.

Key Dates

Start date
Mar 21, 2024
Status verified
Mar 2024
Primary completion
Sep 30, 2027
Completion
Jun 30, 2029

Study Design

Enrollment
152 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Part 1a (safety run-in module 0)
    Patients with HER2-low ABC who have progressed on T-DXd. Patients in part 1a will receive intravenous infusion of HER3-DXd monotherapy (5.6 mg/kg every 21 days)
  • Experimental: Part 1b (dose finding module 1 + dose expansion module 0)
    In the dose expansion part, patients will receive the RP2D defined in the dose finding part of different combinations (module 1) and HER3-DXd single agent 5.6 mg/kg IV D1 every 21 days in module 0.
  • Experimental: Part 2 (dose expansion module 1 + module 0)
    In the dose expansion part, patients will receive the RP2D defined in the dose finding part of different combinations (module 1) and HER3-DXd single agent 5.6 mg/kg IV D1 every 21 days in module 0.

Primary Outcome Measure

DLTs (dose-limiting toxicity) for part 1a and 1b [ Time Frame: 21 months after the beginning of enrolment ]

Central Contacts

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