HER3-DXd (Patritumab Deruxtecan; U3-1402) in Combination With Osimertinib in Subjects With Locally Advanced or Metastatic EGFR-mutated Non-Small Cell Lung Cancer

Part of paid clinical trials in Santa Monica, California.

Sponsor
Daiichi Sankyo
Study ID
NCT04676477
Phase
PHASE1
Status
Active Not Recruiting

Conditions

  • Non-Small Cell Lung Cancer (NSCLC)

Eligibility Criteria

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

Interventions

  • HER3-DXd — DRUG
    Intravenous infusion at a starting dose of 3.2 mg/kg Q3W
  • HER3-DXd — DRUG
    Intravenous infusion at RCD 1 (and at RCD 2 if two provisional RCDs are selected in dose escalation)
  • Osimertinib — DRUG
    Oral administration at 40 mg or 80 mg once daily
  • Osimertinib — DRUG
    Oral administration at RCD 1 (and at RCD 2 if two provisional RCDs are selected in dose escalation)
  • HER3-DXd — DRUG
    Intravenous infusion 5.6 mg/kg Q3W
  • HER3-DXd — DRUG
    Intravenous infusion 4.8 mg/kg Q3W
  • Osimertinib — DRUG
    Oral administration at 80 mg once daily

Study Details

This study includes a Dose Escalation Part to identify the recommended combination dose (RCD) and a Dose Expansion Part to further evaluate efficacy and safety. The primary objectives: Dose Escalation: To assess the safety and tolerability of HER3-DXd (patritumab deruxtecan; U3-1402) and osimertinib in subjects with locally advanced or metastatic non-small cell lung cancer (NSCLC) with an EGFR exon 19 deletion or L858R mutation with tumor progression after treatment with osimertinib, and to determine the recommended combination dose (RCD). Second-Line Dose Expansion Arm 1 and Arm 1b: To assess the preliminary antitumor activity of HER3-DXd and osimertinib in subjects with locally advanced or metastatic NSCLC with an EGFR exon 19 deletion or L858R mutation with tumor progression after treatment with osimertinib. Note: One or both of the study arms may open with one or two distinct dosing schedules. Second-Line Dose Expansion Arm 2: To assess the preliminary antitumor activity of HER3-DXd monotherapy in subjects with locally advanced or metastatic NSCLC with an EGFR exon 19 deletion or L858R mutation with tumor progression after treatment with osimertinib. First-Line Dose Expansion Cohorts 3, 4a, and 4b: To assess the preliminary antitumor activity of HER3-DXd and osimertinib in subjects with locally advanced or metastatic NSCLC with an EGFR exon 19 deletion or L858R mutation without prior systemic treatment for locally advanced or metastatic disease.

Key Dates

Start date
Jun 11, 2021
Status verified
Jun 2025
Primary completion
Jan 31, 2025
Completion
Apr 30, 2027

Study Design

Enrollment
246 participants (actual)
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Dose Escalation: HER3-DXd + osimertinib
    Participants in the Dose Escalation phase will receive HER3-DXd IV Q3W + osimertinib PO once daily. The dose of HER3-DXd in the first cohort will be 3.2 mg/kg Q3W. The dose of osimertinib in the first cohort will be 80 mg PO once daily.
  • Experimental: Second-line Dose Expansion: HER3-DXd + osimertinib (RCD)
    Participants in the Second-line Dose Expansion phase will be randomized to receive HER3-DXd + osimertinib at the RCD
  • Experimental: Second-line Dose Expansion: HER3-DXd
    Participants in the Second-line Dose Expansion phase will be randomized to receive HER3-DXd 5.6 mg/kg IV Q3W
  • Experimental: First-line Dose Expansion: HER3-DXd + osimertinib (Cohort 3; RCD)
    If the RCD includes an osimertinib dose of 80 mg PO once daily, then participants will receive treatment with HER3-DXd and osimertinib at the RCD
  • Experimental: First-line Dose Expansion: HER3-DXd + osimertinib (Cohort 4a)
    Participants in the First-line Dose Expansion phase will be randomized to receive HER3-DXd 5.6 mg/kg IV Q3W and osimertinib dose of 80 mg PO once daily.
  • Experimental: First-line Dose Expansion: HER3-DXd + osimertinib (Cohort 4b)
    Participants in the First-line Dose Expansion phase will be randomized to receive HER3-DXd 4.8 mg/kg IV Q3W and osimertinib dose of 80 mg PO once daily.

Primary Outcome Measure

Dose Escalation: Incidence of Dose-limiting Toxicities (DLT), Treatment-emergent Adverse Events (TEAE), Serious Adverse Events (SAE), Adverse Events of Special Interest (AESI) [ Time Frame: From signing of informed consent form up to 40 days (+7 days) after the last dose of study drugs, up to approximately 9 months ]

Locations (13)

FacilityCityStateZIPSite coordinators
UCLASanta MonicaCalifornia90404-
Yale University School of Medicine - Yale-New Haven HospitalNew HavenConnecticut06510-
Georgetown University Medical CenterWashington D.C.District of Columbia20057-
Northwestern University Feinberg School of MedicineChicagoIllinois60611-
Dana-Farber Cancer InstituteBostonMassachusetts02215-
Massachusetts General Hospital Cancer CenterBostonMassachusetts02114-
Henry Ford Cancer InstituteDetroitMichigan48202-
Dartmouth-Hitchcock Medical CenterLebanonNew Hampshire03756-
Columbia University Irving Medical CenterNew YorkNew York10032-
Memorial Sloan Kettering Cancer CenterNew YorkNew York10065-
University of PennsylvaniaPhiladelphiaPennsylvania19104-
Sarah Cannon and HCA Research InstituteNashvilleTennessee37203-
Virginia Cancer Specialists, PCFairfaxVirginia22031-

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By research site
UCLA· Santa Monica, CAYale University School of Medicine - Yale-New Haven Hospital· New Haven, CTGeorgetown University Medical Center· Washington D.C., DCNorthwestern University Feinberg School of Medicine· Chicago, ILDana-Farber Cancer Institute· Boston, MAMassachusetts General Hospital Cancer Center· Boston, MA

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