Study of T-DXd and Immunotherapy for HER2+ Lung Cancer
This study is looking at the safety of combining trastuzumab deruxtecan (T-DXd) with immunotherapy drugs (like durvalumab, volrustomig, or rilvegostomig), sometimes with chemotherapy (cisplatin or carboplatin), for people with advanced non-small cell lung cancer that has too much of a protein called HER2. The study wants to find the best and safest dose of these combinations. You might be able to join if your cancer has progressed after other treatments or if you have certain types of cancer without specific genetic changes. The study will also look at how well these treatments work. The current status of this study is unclear, and it plans to enroll 304 people.
- Study design
- This is an interventional study, meaning participants will receive specific treatments. It involves different parts, including dose escalation and expansion, to find the safest and most effective drug combinations.
- What's involved
- Not specified in the trial record.
- Compensation
- Not stated in the trial record.
- Follow-up
- Safety and tolerability will be assessed for approximately 20 months from when you give your informed consent.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT04686305
Phase Ib Study of the Safety of T-DXd and Immunotherapy Agents With and Without Chemotherapy in Advanced or Metastatic HER2+, Non-squamous NSCLC
Recruiting
PHASE1Ages 18+InterventionalTreatmentAstraZeneca
~304 participants
Updated 2026-04-13 on ClinicalTrials.gov
What's tested:T-DXdDurvalumabCisplatinCarboplatinPemetrexedVolrustomig
At a glance
Recruiting sites
47 of 91 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Frequency of AEs and SAEs
Measured over Safety and tolerability (and to determine RP2D) will be assessed for approximately 20 months from informed consent
Conditions
Where it's being run
91 sites across 28 statesPhilippines9
Taiwan8
China6
South Korea6
Thailand6
France5
Italy5
Poland5
Who to contact
Opens a ready-to-send draft in your own email app — review before sending.
Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Histologically documented unresectable locally advanced/metastatic non-squamous NSCLC
Part 1: Progression after 1 or 2 lines of systemic therapy for recurrent or metastatic setting.
Part 3, Part 4 and Part 5: Patients must have tumors that do not harbor known genomic alterations or actionable driver kinases, for which approved therapies are available are allowed.
Part 3, Part 4 and Part 5: Patient must be treatment-naïve for advanced or metastatic NSCLC. Patients who have received prior adjuvant, or neoadjuvant chemotherapy, or definitive chemoradiation for advanced disease are eligible, provided that progression has occurred \> 6 months from end of last therapy
HER2overexpression status as determined by central review of tumor tissue
WHO / ECOG performance status of 0 or 1
Measurable target disease assessed by the investigator using RECIST 1.1
Has protocol defined adequate organ and bone marrow function
Part 3, Part 4 and Part 5: Minimum body weight of 35 kg.
Exclusion
HER2 mutation if previously known
Has a history of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder and prior pneumonectomy
Active primary immunodeficiency known HIV infection, or active chronic and resolved hepatitis B (positive hepatitis B virus surface antigen \[HBsAg+ve\] or hepatitis B virus core antibody (anti-HBc +ve) regardless of HBV DNA level)) or hepatitis C infection. Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Patients should be tested for HIV prior to treatment assignment if required by local regulations or IRB/EC
Active infection including tuberculosis and uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
Spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms
Medical history of myocardial infarction within 6 months before treatment assignment, symptomatic CHF (New York Heart Association Class II to IV), clinically important cardiac arrhythmias, or a recent (\< 6 months) cardiovascular event including stroke
For Part 3, Part 4 and Part 5: Cardiomyopathy of any etiology, symptomatic CHF (as defined by New York Heart Association Class \> II), unstable angina pectoris, history of MI within the past 12 months, or cardiac arrhythmia are to be excluded. Patients with troponin levels above ULN at screening (as defined by the manufacturer), and without any myocardial related symptoms, should have a cardiologic consultation before treatment assignment to rule out acute cardiopulmonary events.
Ascites or pericardial effusion that requires drainage, peritoneal shunt, Pleuroperitoneal shunt or CART (Concentrated Ascites Reinfusion Therapy)
For Part 3, Part 4 and Part 5: Active non-infectious skin disease (including any grade rash, urticarial, dermatitis, ulceration, or psoriasis) requiring systemic treatment, active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment.
Unresolved toxicities not yet resolved to Grade ≤ 1 or baseline from previous anticancer therapy OR prior discontinuation of any planned study therapy due to toxicity.
must not have any medical contraindication to platinum-based chemotherapy.
Part 3, Part 4 and Part 5 patients must not have had prior exposure to anti-PD-1, anti-PD-L1, anti-CTLA-4, anti-TIGIT or any other experimental immunotherapy in any setting.
For Part 3, Part 4 and Part 5: History of substance abuse or any other medical or psychological conditions that may, in the opinion of the Investigator, interfere with the subject's participation in the clinical study or evaluation of the clinical study results
For Part 3, Part 4 and Part 5: History of thromboembolic events within 3 months before the first dose of IP (limited to pulmonary embolism, deep vein thrombosis, or cerebral venous sinus thrombosis).
What this trial measures
- Frequency of AEs and SAEsSafety and tolerability (and to determine RP2D) will be assessed for approximately 20 months from informed consent
Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0