Actively Recruiting
A Phase II Trial of Neoadjuvant Trastuzumab Deruxtecan for Patients With Stage II-III HER2-Amplified or HER2-Mutated Non-Small Cell Lung Cancer (HERCULES)
Led by Memorial Sloan Kettering Cancer Center · Updated on 2026-02-23
14
Participants Needed
10
Research Sites
N/A
Total Duration
On this page
Sponsors
M
Memorial Sloan Kettering Cancer Center
Lead Sponsor
A
AstraZeneca
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are studying people with HER2-amplified or HER2-mutated non-small cell lung cancer (NSCLC) to see how many experience a reduction in tumor activity after receiving trastuzumab deruxtecan before surgery. This trial focuses on patients with Stage II, IIIA, or selected IIIB NSCLC. The goal is to evaluate the major pathologic response rate within one year after treatment. Participants receive trastuzumab deruxtecan, a drug that targets HER2, before undergoing routine surgery to remove tumors. The study includes patients whose tumors show specific HER2 mutations or amplifications confirmed by molecular testing. Treatment is given prior to surgery, and additional adjuvant therapy may be provided after surgery at the physician's discretion. During the study, participants undergo various assessments including pulmonary function tests, echocardiograms, and laboratory tests to ensure fitness for surgery and monitor safety. Researchers measure tumor response and evaluate major pathologic response rates up to one year. Participants will be closely monitored throughout the treatment and follow-up periods to assess outcomes and any treatment effects.
CONDITIONS
Brief Title
A Study of Trastuzumab Deruxtecan in People With Non-Small Cell Lung Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Signed informed consent form
- Age 18 years or older
- Able to comply with study protocol
- Pathologically confirmed NSCLC, Stage II, IIIA, or selected IIIB
- Molecular test showing HER2 mutation or amplification
- Measurable disease as defined by RECIST v1.1
- Tumor with solid or subsolid appearance on CT (not purely ground-glass opacity)
- Evaluated by surgeon as medically operable with completely resectable tumor
- Adequate pulmonary function for surgery
- Echocardiogram LVEF 50% or higher within 28 days before enrollment
- ECOG Performance Status of 0 or 1
- Adequate blood counts and organ function within 14 days before treatment
- Use of effective contraception during and 4.5 months after treatment for those with childbearing potential
- Willingness and ability to comply with study visits and procedures
You will not qualify if you...
- NSCLC that is T4 due to mediastinal invasion or IIIB with N3 disease
- Need for total pneumonectomy to achieve complete resection
- Previous lung cancer treatment within 3 years
- Previous lung cancer remission less than 3 years except certain low-risk types
- History or presence of interstitial lung disease or pneumonitis requiring steroids
- Significant lung disorders like recent pulmonary embolism, severe asthma, COPD, restrictive lung disease, or pleural effusion
- Autoimmune or inflammatory disorders with pulmonary involvement
- Previous complete pneumonectomy
- Uncontrolled infection needing IV antibiotics or antivirals
- Active immunodeficiency, uncontrolled HIV, or active hepatitis B or C infection
- Prolonged QT interval on ECG
- Receipt of live attenuated vaccine within 30 days before study drug
- Allergy to study drug or excipients
- Severe hypersensitivity to monoclonal antibodies
- Substance abuse or medical conditions increasing safety risk
- Major surgery within 28 days before treatment
- Other malignancies within 3 years except low-risk or managed cancers
- Use of investigational agents within 4 weeks before treatment
- History of serious cardiac conditions
- Social or geographic factors interfering with participation
- Medical conditions increasing risk of toxicity
- Pregnant or lactating or intending pregnancy during study; negative pregnancy test required for women of childbearing potential
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
Duration - Up to the time before surgery as per protocol
Participants receive neoadjuvant treatment with trastuzumab deruxtecan, a HER2-targeting antibody-drug conjugate.
Trial Site Locations
Total: 10 locations
1
University of Michigan (Data Collection Only)
Ann Arbor, Michigan, United States, 48109
Not Yet Recruiting
2
Mayo Clinic (Data Collection Only)
Rochester, Minnesota, United States, 55905
Not Yet Recruiting
3
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
Basking Ridge, New Jersey, United States, 07920
Actively Recruiting
4
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
Middletown, New Jersey, United States, 07748
Actively Recruiting
5
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
Montvale, New Jersey, United States, 07645
Actively Recruiting
6
Memorial Sloan Kettering Suffolk-Commack (Limited Protocol Activities)
Commack, New York, United States, 11725
Actively Recruiting
7
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
Harrison, New York, United States, 10604
Actively Recruiting
8
Memorial Sloan Kettering Cancer Center (All Protocol Activites)
New York, New York, United States, 10065
Actively Recruiting
9
Memorial Sloan Kettering Nassau (Limited Protocol Activites)
Rockville Centre, New York, United States, 11553
Actively Recruiting
10
Centre Hospitalier de l'Université de Montreal (Data Collection Only)
Montreal, Quebec, Canada, H2L 4M1
Not Yet Recruiting
Research Team
J
James Isbell, MD
J
Jamie Chaft, MD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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