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Osimertinib before radiation and as maintenance for chemo-ineligible Stage III EGFR‑mutant unresectable NSCLC

Phase II, Single-arm Multicenter Study of Osimertinib Induction Before Radiotherapy and Maintenance in Chemo-ineligible or Refusing Patients With Stage III, Unresectable NSCLC and EGFR Mutation-positive Tumors

Phase 2 Interventional AstraZeneca · NCT07295821

This phase 2 trial will test whether giving osimertinib before definitive radiation and continuing it afterward helps adults with Stage III unresectable EGFR‑mutant NSCLC who can't or won't have chemotherapy.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment60 (estimated)
Ages18 Years and up
SexAll
SponsorAstraZeneca Industry-sponsored
Drugs / interventionsosimertinib, chemotherapy, immunotherapy, radiation
Locations20 sites (Beijing and 19 other locations)
Trial IDNCT07295821 on ClinicalTrials.gov

What this trial studies

This is a single-arm phase 2 study giving osimertinib as an induction therapy for up to 12 weeks, followed by about 6 weeks of definitive radiotherapy and then continuous osimertinib maintenance until disease progression or death. The trial enrolls adults with unresectable Stage III non-small cell lung cancer harboring common EGFR mutations (exon 19 deletion or L858R) who are ineligible for or refuse chemotherapy. Patients will be followed for two years after the last patient enrolls, with scheduled visits during induction, frequent visits during radiotherapy, and visits every 12 weeks during maintenance. The primary focus is on efficacy and safety outcomes in this chemo-ineligible population.

Who should consider this trial

Good fit: Adults with Stage III unresectable NSCLC that has an EGFR exon 19 deletion or L858R mutation who are not candidates for, or who refuse, chemotherapy are the intended participants.

Not a fit: Patients without the specified common EGFR mutations, those who can receive standard concurrent chemoradiation, or those with prior systemic therapy are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could provide a non-chemotherapy systemic option that improves local control and delays progression for patients who cannot tolerate or decline chemotherapy.

How similar studies have performed: Osimertinib has well-established activity in metastatic EGFR-mutant NSCLC and EGFR tyrosine kinase inhibitors have been combined with radiation in small studies, but using osimertinib as induction followed by maintenance in chemo-ineligible Stage III disease is relatively novel and not yet proven.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

1. Participant must be ≥ 18 years or the legal age of consent in the jurisdiction in which the study is taking place, at the time of signing the informed consent form.
2. Participants with histologically documented NSCLC of predominantly nonsquamous, squamous, and adenosquamous pathology who present with locally advanced, unresectable (Stage III, according to Version 8 of the IASLC Staging Manual in Thoracic Oncology) disease. It is recommended but not required that except for overt cT4 disease, nodal status N2, or N3 should have been proven by biopsy, via endobronchial ultrasound, mediastinoscopy, thoracoscopy, or in absence of biopsy, should have been confirmed with whole body contrast-enhanced CT.
3. Participants who had recurred from Stage I/II/III after complete surgery or had gross incomplete resections can be included if they didn't receive treatment with any chemotherapy, radiation therapy, immunotherapy, targeted therapy, or investigational agents.
4. Participants with availability of the EGFRm test results confirming that the tumor harbors 1 of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations including de novo T790M
5. WHO performance status of 0, 1 or 2 with no deterioration over the previous 2 weeks prior to baseline at screening and prior to first dose.
6. Participants who are eligible for and planning to undergo RT treatment per physician assessment.
7. Participant refusal or ineligible for chemotherapy per physician assessment.
8. Minimum life expectancy of \> 12 weeks at Day 1.
9. At least one lesion that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes, which must have short axis ≥ 15 mm) with CT or MRI and is suitable for accurate repeated measurements.
10. Capable of giving signed informed consent as described which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

Exclusion Criteria

1. Any presence of small cell and mixed small-cell and non-small cell histology.
2. Past medical history of ILD, drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD.
3. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the participant to participate in the trial or which would jeopardize compliance with the protocol, or active infection.
4. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of osimertinib.
5. History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥ 2 years before the first dose of study intervention and of low potential risk for recurrence. Exceptions include adequately resected non-melanoma skin cancer and curatively treated in situ disease. Patients who have received RT with overlapping fields (eg, cured breast cancer) should be excluded.
6. Patient meets any of the following cardiac criteria: Mean resting QTc \> 470 msec, obtained from 3 ECGs, using the screening clinic ECG machine-derived QTc value.
7. Inadequate bone marrow reserve or organ function.
8. Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study treatment with the exception of alopecia and Grade 2 prior platinum-therapy related neuropathy. Prior treatment with any chemotherapy, radiation therapy, immunotherapy, targeted therapy, or investigational agents for locally advanced, unresectable Stage III NSCLC. Prior surgical resection (ie, Stage I, II, or III) with no systemic treatment with residual disease or a recurrence is permitted.

11 Prior exposure to EGFR-TKI therapy. 12 Major surgical procedure (excluding placement of vascular access) or significant traumatic injury within 4 weeks of the first dose of study intervention or an anticipated need for major surgery during the study.

13 Participation in another clinical study with a study intervention or investigational medicinal device administered in the last 4 weeks.

14 History of hypersensitivity to active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib.

15 History of hypersensitivity to active or inactive excipients of RT. 16 Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).

17 Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements.

18 Previous enrolment in the present study. Rescreening of individuals who were screen failures is allowed.

19 For females only - currently pregnant (confirmed with positive pregnancy test) or breastfeeding.

20 Patients should refrain from breastfeeding from enrolment throughout the study and until 6 weeks after last dose of study intervention.

Where this trial is running

Beijing and 19 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
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Conditions Lung CancerNSCLC
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.