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

First listed
Mar 7, 2024
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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