Treating Early-stage Non-Small Cell Lung Cancer With Durvalumab and Radiation Therapy

NCT04716946 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 20-415
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 9

Brief Summary

The purpose of this study is to find out whether treatment with the study drug durvalumab combined with a type of radiation therapy called stereotactic body radiation (SBRT) is a more effective treatment for early-stage non-small cell lung cancer (NSCLC) than SBRT alone.

Conditions

NSCLC; Non-small Cell Lung Cancer; Lung Cancer; Non-small Cell Lung Cancer Stage I; Non-small Cell Lung Cancer Stage II; Non-small Cell Lung Cancer Stage III; Non-small Cell Lung Cancer Stage IIIA; PD-L1 Gene Mutation

Keywords

Durvalumab; NSCLC; Non-small Cell Lung Cancer; Non-small Cell Lung Cancer Stage I; Non-small Cell Lung Cancer Stage II; Non-small Cell Lung Cancer Stage III; Non-small Cell Lung Cancer Stage IIIA; Lung Cancer; PD-L1 Gene Mutation; Early stage NSCLC; 20-145; Memorial Sloan Kettering Cancer Center

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  The primary objective of the study is to evaluate 2- year progression-free survival (PFS) per RECIST 1.1 with durvalumab combined with stereotactic body radiation therapy (SBRT) compared to historical controls with SBRT alone.

  2 years

Study Arms (1)

Participants with Early-stage Non-Small Cell Lung Cancer

EXPERIMENTAL

Participants will be diagnosed with Stage I-IIIA NSCLC and will be ineligible for surgery and will have any level of PD-L1

Drug: Durvalumab; Radiation: Stereotactic Body Radiation Therapy

Interventions

Durvalumab DRUG

Patients will receive durvalumab 1500mg durvalumab via IV infusion over 1 hour, once every 4 weeks (Q4W) for up to a maximum of 6 months (up to 6 doses/cycles) unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met.

Participants with Early-stage Non-Small Cell Lung Cancer

Stereotactic Body Radiation Therapy RADIATION

Radiation therapy will be performed with external beam ionizing radiation in accordance with institutional standard practice. 3D conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT) or volumetric arc therapy (VMAT) will be used at the discretion of the treating radiation oncologist.

Also known as: SBRT

Participants with Early-stage Non-Small Cell Lung Cancer

Eligibility Criteria

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

You may qualify if:

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization obtained from the patient/legal representative prior to performing any protocol- related procedures.
• Patient age ≥ 18 at time of consent
• Early stage NSCLC (Stage I to IIIA; T1-4 excluding patients with satellite nodules in the same or ipsilateral lobes, N0; AJCC 8th edition)
• Ineligible for or unwilling to undergo surgical resection. Reasons for surgical ineligibility include: medically inoperable or surgically unresectable (due to tumor size, location etc.), as assessed by MSKCC thoracic surgeon or multi-disciplinary tumor board consensus. Reasons for ineligibility or patient's unwillingness to undergo surgical resection must be clearly documented.
• Histological and/or cytological confirmation of NSCLC as per standard of care biopsy; no additional research protocol-specific biopsy is needed.
• ECOG/WHO PS 0-1 (KPS 70-100)
• Candidates for definitive SBRT
• ° If, after candidates have been planned for RT, they are unable to be treated with the institutional dose constraints as listed in the appendix, they will be labeled ineligible and removed from the study. Ineligible patients will be replaced.
• A predicted 2-year PFS of \<80% (≥20% risk for disease progression) based on an MSKCC-developed radiomics risk prediction model (see section 9.0).
• Body weight \> 30kg
• Adequate normal organ and marrow function as defined below:
• Hemoglobin ≥9.0 g/dL
• Absolute neutrophil count (ANC) 1.5 x (\> 1500 per mm\^3)
• Platelet count ≥75 x 10\^9/L (\>75,000 per mm\^3)
• Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.

You may not qualify if:

• Participation in another clinical study with an investigational product during the last 4 weeks.
• Previous thoracic radiation precluding definitive SBRT to the current tumor.
• 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:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 5 years may be included but only after consultation with the PI
• Patients with celiac disease controlled by diet alone
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the PI.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the PI.
• Prior/Current Therapies:
• Treatment with a monoclonal antibody within 4 weeks prior to study Day 1 or has not recovered (i.e., ≥ Grade 1 at baseline) from adverse events due to agents administered \> 4 weeks earlier (intraocular bevacizumab is acceptable).
• Prior chemotherapy or targeted small molecule therapy, within 3 weeks prior to study Day 1 or has not recovered (i.e., ≥ Grade 1 at baseline) from adverse events due to a previously administered agent).
• Prior therapy with an anti-PD-1, anti-PD-L1, including durvalumab, anti-PDL2, anti-CD137, anti-Cytotoxic T- lymphocyte-associated antigen-4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• AstraZeneca: collaborator

Study Sites (9)

Hartford Healthcare (Data Collection)

Hartford, Connecticut, 06102, United States

Location

Baptist Alliance - McI

Miami, Florida, 33143, United States

Location

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Cancer Center @ Suffolk - Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau

Rockville Centre, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

durvalumab; Radiosurgery

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Charles Simone, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2021
• First Posted: January 20, 2021
• Study Start: January 27, 2021
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027
• Last Updated: March 4, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (9)