Neoadjuvant Durvalumab and Chemotherapy Followed by Surgery/CRT and Durvalumab in Borderline Resectable Stage III NSCLC

NCT06998719 | Not Yet Recruiting Phase 2

• 1 other identifier: NCC5253
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase II, interventional study of neoadjuvant durvalumab (MEDI 4736) and platinum-based Chemotherapy, followed by either surgery and adjuvant durvalumab or chemoradiotherapy (CRT) and consolidation durvalumab, in participants with borderline resectable stage III Non-small Cell Lung Cancer (NSCLC) (ACCESS)

Conditions

Non-small Cell Lung Cancer Stage III; Borderline Resectable Carcinoma

Keywords

Neoadjuvant therapy; Non-small Cell Lung Cancer; Borderline Resectable Carcinoma

Outcome Measures

Primary Outcomes (1)

• Resection rate

  To assess the efficacy of neoadjuvant durvalumab + chemotherapy in terms of resection rate in participants with borderline resectable stage III NSCLC.

  Through study completion, an average of 1 year.

Secondary Outcomes (1)

• R0 resection rate.

  Through study completion, an average of 1 year.

Study Arms (2)

Cohort 1 (Surgery)

EXPERIMENTAL

After 2 cycles of neoadjuvant durvalumab (1500 mg) + chemotherapy, multidisciplinary team (MDT)-determined participants with resectable tumor (according to MDT re-assessment) will receive a further 1-2 cycles of neoadjuvant durvalumab + chemotherapy followed by surgery. Participants should only go onto surgical resection if the MDT evaluation indicates that an R0 resection is feasible. After surgery, patients will then go on to receive adjuvant durvalumab 1500 mg q4w until recurrence or up to one year (maximum 12 cycles) unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met.

Drug: Durvalumab

Cohort 2 (CRT)

ACTIVE COMPARATOR

Participants with unresectable tumor (according to MDT re-assessment) will receive CRT. Participants will receive platinum-based chemotherapy for a maximum of 2 cycles. Radiotherapy at a dose of 5 fractions/week for \~6 weeks (± 3 days) (total 60 Gy± 10%) can be given sequentially or concurrently with chemotherapy. After CRT, patients will receive consolidation durvalumab 1500 mg q4w until disease progression or up to one year (maximum 12 cycles) unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met.

Drug: Durvalumab

Interventions

Durvalumab DRUG

Neoadjuvant durvalumab (MEDI 4736)and platinum-based chemotherapy, followed by either surgery and adjuvant durvalumab or CRT and consolidation durvalumab, in borderline resectable stage III NSCLC

Also known as: Surgery, Chemoradiotherapy (CRT)

Cohort 1 (Surgery); Cohort 2 (CRT)

Eligibility Criteria

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

You may qualify if:

• \. Participant must be ≥ 18 years, at the time of screening. 2. Histologically or cytologically documented NSCLC. 3. Deemed borderline resectable at baseline, confirmed by MDT evaluation at diagnosis.
• \. Previously untreated and pathologically confirmed stage III (according to Version 8 of the IASLC Staging Manual in Thoracic Oncology2016)
• Nodal status should be investigated with whole body FDG-PET, plus contrast-enhanced computed tomography, and it is optional and decided by investigator that nodal status be proven by biopsy via endobronchial ultrasound, mediastinoscopy, or thoracoscopy.
• Mandatory brain MRI with IV contrast, if not available, it is mandatory to take brain computed tomography with IV contrast at the time of staging.
• \. WHO or ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to baseline or day of first dose.
• \. Participants must have been confirmed as EGFR/ALK wild type via an appropriately validated local test. Participants with known sensitising EGFR mutations or ALK rearrangements are excluded from the study.
• \. At least one lesion not previously irradiated that qualifies as a RECIST 1.1 TL at baseline and can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes, which must have short axis ≥ 15 mm) with computed tomography or MRI and is suitable for accurate repeated measurements.
• \. Adequate organ and bone marrow function as follows:
• Haemoglobin ≥ 9.0 g/dL.
• Absolute neutrophil count ≥ 1.5 × 109/L.
• Platelet count ≥ 100×109/L.
• Serum bilirubin ≤ 1.5×the ULN or ≤ 3×ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinaemia).
• Alanine aminotransferase and AST ≤ 2.5×ULN.
• Calculated CrCL \> 40 mL/min as determined by Cockcroft Gault (using actual body weight).
• Males:

You may not qualify if:

• Existence of more than one primary tumor, such as: mixed small cell and NSCLC histology; synchronous or metachronous tumors that could represent distinct primary tumors.
• History of another primary malignancy except for malignancy treated with curative-intent with no known active disease ≥ 5 years before the first dose of study intervention and of low potential risk for recurrence, basal cell carcinoma of the skin, squamous cell carcinoma of the skin or lentigo maligna that has undergone potentially curative therapy or adequately treated carcinoma in situ without evidence of disease.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, colitis or Crohn's disease\], systemic lupus erythematosus, sarcoidosis, granulomatosis with polyangiitis, Graves ' disease, rheumatoid arthritis, hypophysitis, uveitis, autoimmune pneumonitis, and autoimmune myocarditis). The following are exceptions to this criterion:
• \- Participants with vitiligo or alopecia.
• \- Participants with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement.
• \- Any chronic skin condition that does not require systemic therapy.
• \- Participants without active disease in the last 5 years may be included but only after consultation with the Study Clinical Lead.
• \- Participants with coeliac disease controlled by diet alone.
• Known active hepatitis infection, positive HCV antibody, HBsAg or HBV core antibody (anti-HBc), at screening. Participants with a past or resolved HBV infection (defined as the presence of anti-HBc and absence of HBsAg) are eligible. Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Participants co-infected with HBV and HCV, or co-infected with HBV and HDV, namely: HBV positive (presence of HBsAg and/or anti-HBcAb with detectable HBV DNA); AND
• HCV positive (presence of anti-HCV antibodies); OR
• HDV positive (presence of anti-HDV antibodies).
• Known to have tested positive for HIV (positive HIV 1 or 2 antibodies) or active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice).
• History of active primary immunodeficiency.
• Investigator judgement of one or more of the following:
• Mean resting corrected QT interval \> 470 ms, obtained from triplicate ECGs performed at screening.

Sponsors & Collaborators

• Bi Nan: lead
• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: collaborator

Study Sites (1)

Cancer Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100021, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

durvalumab; Surgical Procedures, Operative; Chemoradiotherapy

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)

Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy

Study Officials

• Jie He, MD

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shu-Hang Wang, MD

CONTACT

8778 8446; cancergcp@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief physician

Study Record Dates

• First Submitted: April 21, 2025
• First Posted: May 31, 2025
• Study Start: July 1, 2025
• Primary Completion: May 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: May 31, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)