Neoadjuvant Immunoradiation for Resectable Non-Small Cell Lung Cancer

NCT03237377 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: J1772IRB00127418ESR-16-12244
• Study Type: interventional
• Target: 9
• Locations: 2 countries
• Sites: 2

Brief 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, 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.

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Toxicities as Measured by Number of Participants Experiencing Adverse Events

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

  3 months post surgery

• 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.

  Up to 3 years

Secondary Outcomes (5)

• Surgical Morbidity and Mortality

  Up to 3 months post-surgery

• Percentage of Participants With Pathologic Response

  Up to 3 years

• Percentage of Participants With Radiologic Response

  Up to 3 years

• Duration of Response as Measured by Recurrence-free Survival

  Up to 3 years

• Overall Survival

  Up to 3 years

Study Arms (2)

Durvalumab with Radiation

EXPERIMENTAL

Drug: 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

Drug: Durvalumab; Radiation: Thoracic Radiation; Procedure: lobectomy; Drug: Standard of care adjuvant chemotherapy

Durvalumab and Trememlimumab with Radiation

EXPERIMENTAL

Drugs: 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

Drug: Durvalumab; Drug: Tremelimumab; Radiation: Thoracic Radiation; Procedure: lobectomy; Drug: Standard of care adjuvant chemotherapy

Interventions

Durvalumab DRUG

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

Also known as: [MEDI4736]

Durvalumab and Trememlimumab with Radiation; Durvalumab with Radiation

Tremelimumab DRUG

75mg via IV infusion every 4 weeks

Also known as: [CP-675 206]

Durvalumab and Trememlimumab with Radiation

Thoracic Radiation RADIATION

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

Durvalumab and Trememlimumab with Radiation; Durvalumab with Radiation

lobectomy PROCEDURE

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

Durvalumab and Trememlimumab with Radiation; Durvalumab with Radiation

Standard of care adjuvant chemotherapy DRUG

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

Durvalumab and Trememlimumab with Radiation; Durvalumab with Radiation

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• AstraZeneca: collaborator

Study Sites (2)

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 21224, United States

Location

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

durvalumab; tremelimumab; Anterior Temporal Lobectomy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Surgical Procedures, Operative; Neurosurgical Procedures

Results Point of Contact

• Title: Jasmine Brooks, Senior Research Program Coordinator
• Organization: Johns Hopkins SKCCC CRO Coordinating Center

jbrook54@jhmi.edu

667-306-8335

Study Officials

• Patrick Forde, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2017
• First Posted: August 2, 2017
• Study Start: December 12, 2017
• Primary Completion: November 4, 2021
• Study Completion: May 23, 2024
• Last Updated: October 14, 2025
• Results First Posted: October 16, 2023

Record last verified: 2025-09

Locations

US (1); CA (1)