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Non-Small Cell Lung CancerPhase 2NCT03237377

Neoadjuvant Immunoradiation for Resectable Non-Small Cell Lung Cancer

A Phase 2 study testing Durvalumab, Tremelimumab and Thoracic Radiation in people with Non-Small Cell Lung Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 2 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is a pilot study of neoadjuvant 'immunoradiation' (durvalumab or durvalumab plus tremelimumab) administered every 4 weeks for 2 doses, concurrently with standard thoracic radiation (RT) (45Gy in 25 fractions), with one dose of immunotherapy alone delivered in the pre-surgical window, prior to surgical resection… Read more about this study

Who is it for?
Ages 18 to 100 years
Conditions the study is for
Non-Small Cell Lung Cancer
What is being tested?
Durvalumab, Tremelimumab and Thoracic Radiation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
2 sitesin 2 countries
Study dates
12 Dec 2017to 23 May 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written informed consent and any locally-required authorization obtained.
  • Histologically-confirmed diagnosis of stage III non-small cell lung cancer (NSCLC)
  • Age≥18 years
  • Life expectancy >6 months
  • Body weight >30kg
  • Subjects with non-small cell lung cancer deemed surgically resectable by an attending thoracic surgeon with lobectomy
Show all 11Show fewer
  • ECOG Performance Status 0-1
  • Normal bone marrow and organ function on routine laboratory tests, as defined in section 4.1
  • Evidence of post-menopausal status or negative urinary/serum pregnancy test for female pre-menopausal subjects. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause.
  • Ability to understand and willingness of sign consent form
  • Willingness to comply with the protocol for the duration of the study

Who cannot join

  • Involvement in the planning and/or conduct of the study (includes AstraZeneca staff and staff at the study site)
  • Prior investigational therapy within 28 days/at least 5 half-lives before study drug administration
  • Prior chest radiation
  • Prior history of interstitial lung disease or pneumonitis requiring corticosteroids, or active non-infectious pneumonitis
  • Patients only suitable for surgical management with pneumonectomy, deemed by an attending thoracic surgeon
  • Prior therapy with PD-1, PD-L1, CTLA-4 or anti-cancer vaccines, including durvalumab and tremelimumab
Show all 27Show fewer
  • Participation in another clinical study with an investigational product in the last 4 weeks or equivalent of 5 half-lives of the first dose of study treatment, whichever is shorter
  • History of another primary malignancy that requires active ongoing treatment or, in the opinion of the investigator, is likely to require treatment within 6 months of trial enrollment
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion:
  • Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
  • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
  • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
  • Any unresolved toxicity (>CTCAE grade 2) from previous anti-cancer therapy
  • Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy)
  • Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable
  • Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug.
  • Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable
  • History of allogenic organ transplantation.
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion (vitiligo or alopecia; hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement; any chronic skin condition that does not require systemic therapy; active disease in the last 5 years may be included but only after consultation with the study physician; celiac disease controlled by diet alone.)
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
  • Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab or tremelimumab
  • Female subjects who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control.
  • Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study result.
  • Known allergy or hypersensitivity to IP or any excipient
  • Uncontrolled psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written consent
  • Any condition that, in the opinion of the investigator would interfere with evaluation of study treatment or interpretation of patient safety or study results.

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

United States1 site

  • Johns Hopkins Bayview Medical Center

    Baltimore, Maryland, 21224

Other trials in United States

Canada1 site

  • Princess Margaret Cancer Centre

    Toronto, Ontario

Other trials in Canada

About this study

Official title: Neoadjuvant Immunoradiation for Stage III Resectable Non-Small Cell Lung Cancer

This is a pilot study of neoadjuvant 'immunoradiation' (durvalumab or durvalumab plus tremelimumab) administered every 4 weeks for 2 doses, concurrently with standard thoracic radiation (RT) (45Gy in 25 fractions), with one dose of immunotherapy alone delivered in the pre-surgical window, prior to surgical resection, for patients with stage IIIA NSCLC that is deemed resectable with a lobectomy by a thoracic surgeon. If preliminary safety of the durvalumab/thoracic RT combination is established, a second cohort investigating the combination of durvalumab/tremelimumab/thoracic RT prior to surgical resection will be opened. After surgical resection, patients may receive standard adjuvant chemotherapy, as deemed appropriate by the treating investigator.

Being tested
Durvalumab, Tremelimumab, Thoracic Radiation, lobectomy, Standard of care adjuvant chemotherapy
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DurvalumabDrug

    Also called [MEDI4736]

    1500mg via IV infusion every 4 weeks for up to 3 doses/cycles

  • TremelimumabDrug

    Also called [CP-675 206]

    75mg via IV infusion every 4 weeks

  • Thoracic RadiationRadiation

    5 days per week in once daily fractionation, 1.8-2.0 Gy per fraction

  • lobectomyProcedure or surgery

    patients may proceed to surgery post drug and radiation intervention for lung lobectomy

  • Standard of care adjuvant chemotherapyDrug

    patients may or may not proceed to adjuvant chemotherapy post trial drug and radiation intervention and surgery

Study groups in NCT03237377
Study groupRoleWhat they receive
Durvalumab with RadiationExperimentalDrug: Durvalumab Other Names: MEDI4736 MEDI4736 1500mg via IV infusion every 4 weeks for up to 3 doses/cycles Intervention: Radiation: Thoracic Radiation 5 days per week in once daily fractionation, 1.8-2.0 Gy per fraction Intervention: Procedure/Surgery: lobectomy patients may proceed to surgery post drug and radiation intervention for lung lobectomy Intervention: Drug: Standard of care adjuvant chemotherapy patients may or may not proceed to adjuvant chemotherapy post trial drug and radiation intervention and surgery
Receives: Drug: Durvalumab; Radiation: Thoracic Radiation; Procedure: lobectomy; Drug: Standard of care adjuvant chemotherapy
Durvalumab and Trememlimumab with RadiationExperimentalDrugs: Durvalumab + Tremelimumab Other Names: MEDI4736 and CP-675 MEDI4736 1500mg via IV infusion every 4 weeks for up to 3 doses/cycles + CP-675 206 75mg via IV infusion every 4 weeks up 3 doses/cycles Intervention: Radiation: Thoracic Radiation 5 days per week in once daily fractionation, 1.8-2.0 Gy per fraction Intervention: Procedure/Surgery: lobectomy patients may proceed to surgery post drug and radiation intervention for lung lobectomy Intervention: Drug: Standard of care adjuvant chemotherapy patients may or may not proceed to adjuvant chemotherapy post trial drug and radiation intervention and surgery
Receives: Drug: Durvalumab; Drug: Tremelimumab; Radiation: Thoracic Radiation; Procedure: lobectomy; Drug: Standard of care adjuvant chemotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Toxicities as Measured by Number of Participants Experiencing Adverse Events

    Number of participants experiencing adverse events as defined by CTCAE v4.0.

    Measured: 3 months post surgery

  2. Feasibility of Preoperative Immunoradiation

    Number of participants with stage III resectable NSCLC who received durvalumab or durvalumab plus tremelimumab concurrently with thoracic radiation (RT) in the pre-surgical window prior to surgical resection, for whom planned surgical resection was not delayed.

    Measured: Up to 3 years

Secondary outcomes (4)

  1. Surgical Morbidity and Mortality

    Number of participants who experience post-operative death. Calculated through log-rank test and Cox proportional hazards (PH) model. The values in the table represent the number of participants who experienced post-operative death.

    Measured: Up to 3 months post-surgery

  2. Percentage of Participants With Pathologic Response

    Percentage of participants with major pathologic response (MPR), partial response (PR) or no response (NR), where MPR is >90% reduction in tumor cells, PR = 10-90% or NR = 0-10%. The percentage of patients whose tumor samples achieve MPR, PR and NR will be tabulated.

    Measured: Up to 3 years

  3. Percentage of Participants With Radiologic Response

    Percentage of participants with complete response (CR), partial response (PR), progressive disease (PD), and stable disease (SD) as defined by RECIST 1.1 and immune-related RECIST criteria when treated with preoperative immunoradiation followed by surgery. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, PD is >20% increase in sum of diameters of target lesions, SD is <30% decrease or <20% increase in sum of diameters of target lesions.

    Measured: Up to 3 years

  4. Overall Survival

    Number of months alive after treatment with preoperative immunoradiation followed by surgery. Calculated through log-rank test and Cox proportional hazards (PH) model.

    Measured: Approximately 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Aug 2017
  2. Study start12 Dec 2017
  3. Primary completion4 Nov 2021
  4. Study completion23 May 2024

Why it stopped: low accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03237377
Sponsor's protocol ID
J1772
Other IDs
IRB00127418, ESR-16-12244
Status last verified
May 2026
First submitted
19 Jul 2017
Last updated
27 May 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Durvalumab, Tremelimumab and Thoracic Radiation in people with Non-Small Cell Lung Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 27 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Toxicities as Measured by Number of Participants Experiencing Adverse Events (time frame: 3 months post surgery). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03237377.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 May 2026.

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Clinical Trial NCT03237377 | AzTrials