Window of Opportunity Trial of Durvalumab (MEDI4736) to Identify Immune Dynamics in Operable Non-small Cell Lung Cancer (NSCLC) (MIRACLE)

NCT05206812 | Active Not Recruiting Phase 2

• 1 other identifier: 4-2021-1621
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This study is phase II, open label, clinical trial of durvalumab to identify immune dynamics in operable non-small cell lung cancer.

Conditions

Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Major pathologic response

  Evaluate the pathologic response in resected tumor tissue. The major pathologic response is defined as less than 10% viable tumors after treatment.

  Right after the surgery

Secondary Outcomes (5)

• Minimal residual disease

  At screening, Post neo-adjuvant durvalamab (+ 1 week ~ prior to surgery), Post-op (3-4 weeks after surgery), Post-op at 3 months (+/- 7 days), Post-op at 6 months (+/- 7 days), After progression (+/- 7 days)

• Locoregional control

  UP to 2years

• Distant metastases free survival

  UP to 3years

• Disease-free survival

  UP to 3years

• Overall survival (OS)

  Up to 5years

Study Arms (1)

durvalumab

EXPERIMENTAL

The operable non-small cell lung carcinoma patients (resectable stage IIA\~IIIB)

Drug: durvalumab

Interventions

durvalumab DRUG

* durvalumab 1500 mg QD\* * Surgery within 1 to 8 weeks - 4 cycles of durvalumab 1500 mg/m2 (Day 1, Day 8)+cisplatin 80 mg/m2 (Day 1) q3wks -durvalumab 1500 mg q4wks (Maximum of 10 cycles)

durvalumab

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed operable NSCLC (resectable stage IIA\~IIIB) regardless of PD-L1 expression.
• At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion (TL) at baseline. Tumor assessment by computed tomography (CT) scan or magnetic resonance imaging (MRI) must be performed within 28 days prior to neoadjuvant durvalumab.
• 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 (eg, Health Insurance Portability and Accountability Act in the US, European Union \[EU\] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
• Male or female, 18 years or older (at the consent is obtained). Note: In the Republic of Korea, a participant must be over 19 years of age inclusive, at the time of signing the informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy of \> 12 weeks
• Body weight \>30 kg
• Adequate normal organ and marrow function as defined below:
• Hemoglobin ≥9.0 g/dL Absolute neutrophil count (ANC) ≥1.0 × 109 /L Platelet count ≥75 × 109/L 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.
• AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN
• Measured creatinine clearance (CL) \>60 mL/min or Calculated creatinine CL\>60 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
• Males:
• Creatinine CL (mL/min) = Weight (kg) x (140 - Age) / 72 x serum creatinine (mg/dL)
• Females:
• Creatinine CL (mL/min) = Weight (kg) x (140 - Age) / 72 x serum creatinine (mg/dL) x 0.85

You may not qualify if:

• Patients with EGFR mutations (identified with local testing).
• Any prior treatment for NSCLC, including prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody, chemo, RT, target therapy or investigational drug.
• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
• B. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician.
• 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.
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP.
• 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:
• A. Patients with vitiligo or alopecia B. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement C. Any chronic skin condition that does not require systemic therapy D. Patients without active disease in the last 5 years may be included but only after consultation with the study physician E. Patients with 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, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
• History of another primary malignancy except for A. Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence B. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease C. Adequately treated carcinoma in situ without evidence of disease
• History of leptomeningeal carcinomatosis
• Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart). Patient safety and the cardiac SKG should be consulted as needed.
• History of active primary immunodeficiency
• 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 CPatients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Yonsei University Health System, Severance Hospital

Seoul, South Korea

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

durvalumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Hye Ryun Hye Ryun

  Severance Hospital

  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: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 11, 2022
• First Posted: January 25, 2022
• Study Start: September 1, 2022
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): July 1, 2028
• Last Updated: January 27, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)