Anti-PD-L1 in Stage IIIA(N2) Non-small Cell Lung Cancer (NSCLC)

NCT02572843 | Completed Phase 2 Results DMC

• 2 other identifiers: SAKK 16/14000001480
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 19

Brief Summary

The objective of the trial is to demonstrate that the addition of neoadjuvant and adjuvant immunotherapy (with the anti-PD-L1 antibody MEDI4736) to standard neoadjuvant chemotherapy (with cisplatin/docetaxel) in primary resectable stage IIIA(N2) NSCLC is efficacious and feasible.

Conditions

NSCLC Non-small Cell Lung Cancer

Keywords

NSCLC; lung cancer; MEDI4736; non-small cell lung cancer; immunotherapy; anti-PD-L1

Outcome Measures

Primary Outcomes (1)

• Event-free Survival (EFS) Rate

  Measured using the Kaplan-Meier method

  at 12 months

Secondary Outcomes (6)

• Median Event-free Survival (EFS)

  up to 7 years from registration

• Overall Survival (OS) Rate

  at 1, 2, 3, 4 & 5 years after registration

• Objective Response (OR) After Neoadjuvant Chemotherapy (FAS)

  After Neoadjuvant Chemotherapy, up to 3 months

• Objective Response (OR) After Neoadjuvant Immunotherapy (FAS II)

  After Neoadjuvant immunotherapy, up to 3 months

• Pathological Responses (pCR)

  at 12 months

Study Arms (1)

MEDI4736

EXPERIMENTAL

Patients whose tumor is deemed resectable at diagnosis will receive 3 cycles (21 days each) of standard chemotherapy with cisplatin/docetaxel followed by 2 cycles (14 days each) of neoadjuvant immunotherapy with MEDI4736 750 mg. Following surgery, patients with complete resection (R0) of their tumor will be administered adjuvant treatment with MEDI4736 750 mg for up to one year or until recurrence, death, unacceptable toxicity or consent withdrawal (whichever occurs first). Patients with incomplete R1/R2 resection, including patients with extracapsular spread of mediastinal lymph node metastases, may undergo standard radiotherapy prior to adjuvant treatment with MEDI4736.

Drug: MEDI4736 (anti-PD-L1)

Interventions

MEDI4736 (anti-PD-L1) DRUG

fixed dosing 750 mg

Also known as: durvalumab

MEDI4736

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent according to ICH-GCP regulations before patient registration and any protocol-related procedures.
• Pathologically proven NSCLC (adeno-, squamous-, large cell carcinoma or NSCLC not otherwise specified) irrespective of genomic aberrations or PD-L1 expression status.
• Tumor tissue is available for the mandatory translational research (preferably histology, cytology allowed).
• Tumor stage T1-3N2M0 (stage IIIA(N2)) according to the TNM classification, 7th edition, (October 2009). Mediastinal lymph node staging has to follow the process chart.
• Tumor is considered resectable based on a multidisciplinary tumor board decision made before neoadjuvant treatment. Resectable is when a complete resection can be achieved according to Rami-Porta {Rami-Porta, 2005 #88}.
• Measurable disease according to RECIST 1.1 criteria (non-nodal lesions ≥10 mm in longest diameter, lymph nodes ≥15 mm in short axis) by PET/CT with contrast enhanced CT-scan.
• WHO performance status 0-1.
• Age 18-75 years at time of registration.
• Appropriate lung function based on the ESTS guidelines {Brunelli, 2009 #19}:
• For pneumonectomy: FEV1 and DLCO ≥80%. If one of both \<80% an exercise test peak VO2 \>75% or 20ml/kg/min is needed,
• For resection less than pneumonectomy (resection up to the calculated extent): exercise test peak VO2 ≥35% or ≥10ml/kg/min, with predicted postoperative FEV1 and DLCO ≥ 30%.
• Adequate hematological values: hemoglobin ≥ 90 g/L, absolute neutrophils count ≥ 1.5 x 109/L, platelets count ≥ 100 x 109/L.
• Adequate hepatic function: bilirubin ≤ 1.5 x ULN, AST/ALT ≤ 1.5 x ULN, AP ≤ 2.5 x ULN.
• Adequate renal function: calculated creatinine clearance ≥ 60 mL/min, according to the formula of Cockcroft-Gault.
• Women with child-bearing potential are using effective contraception are not pregnant or lactating and agree not to become pregnant during participation in the trial and during 90 days after the last treatment. A negative serum pregnancy test performed within 7 days before registration into the trial is required for all women with child-bearing potential. Men agree not to father a child during participation in the trial and during 90 days after the last treatment.

You may not qualify if:

• Presence of any distant metastasis or N3 disease. Brain metastases have to be excluded by CT or MRI.
• Sulcus superior tumors (Pancoast tumors).
• Previous or concomitant malignancy within 5 years prior registration with the exception of adequately treated localized non-melanoma skin cancer or cervical carcinoma in situ.
• Any previous treatment for NSCLC.
• Any previous treatment with a PD-1 or PD-L1 inhibitor, including MEDI4736.
• Previous radiotherapy to the chest.
• Absolute contraindications for the use of corticosteroids as premedication.
• Concurrent treatment with other experimental drugs or other anti-cancer therapy, treatment in a clinical trial within 30 days prior to registration.
• Current or prior use of immunosuppressive medication within 28 days before the first dose of MEDI4736, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses (i.e. which must not exceed 10 mg/day of prednisone or an equivalent corticosteroid) and the premedication for chemotherapy.
• Severe or uncontrolled cardiac disease requiring treatment, congestive heart failure NYHA III or IV, unstable angina pectoris even if medically controlled, history of myocardial infarction during the last 3 months, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia).
• Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Bazett's Correction.
• Preexisting peripheral neuropathy (\> grade 1).
• Body weight less than 30 kg.
• Active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease or a syndrome that requires systemic steroids or immunosuppressive agents. Exceptions: - Vitiligo or resolved childhood asthma/atopy - Hypothyroidism stable on hormone replacement or Sjorgen's syndrome
• Active or prior documented inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis).

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (19)

Stadtspital Triemli

Zurich, Canton of Zurich, 8063, Switzerland

Location

Kantonsspital Aarau

Aarau, CH-5001, Switzerland

Location

Kantonsspital Baden

Baden, 5404, Switzerland

Location

St. Claraspital Basel

Basel, 4016, Switzerland

Location

Universitaetsspital Basel

Basel, 4031, Switzerland

Location

IOSI Ospedale Regionale di Bellinzona e Valli

Bellinzona, 6500, Switzerland

Location

Inselspital Bern

Bern, CH-3010, Switzerland

Location

Kantonsspital Graubuenden

Chur, CH-7000, Switzerland

Location

Spital Thurgau AG

Frauenfeld, CH-8500, Switzerland

Location

Hopital Fribourgeois HFR

Fribourg, 1708, Switzerland

Location

Hopital Cantonal Universitaire de Geneve

Geneva, CH-1211, Switzerland

Location

CCAC Lausanne

Lausanne, 1004, Switzerland

Location

Centre hospitalier universitaire vaudois CHUV

Lausanne, CH-1011, Switzerland

Location

Luzerner Kantonsspital

Lucerne, CH-6000, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

Regionalspital

Thun, 3600, Switzerland

Location

Kantonsspital Winterthur

Winterthur, CH-8401, Switzerland

Location

Klinik Hirslanden Onkozentrum Zürich

Zurich, CH-8032, Switzerland

Location

UniversitaetsSpital Zuerich

Zurich, CH-8091, Switzerland

Location

Related Publications (2)

• Schmid D, Sobottka B, Manzo M, Trub M, Leonards K, Herzig P, Oyewole OR, Jermann P, Hayoz S, Savic Prince S, Tochtermann G, Natoli M, Pless M, Bettini A, Fruh M, Mauti LA, Britschgi C, Peters S, Mark M, Ochsenbein AF, Janthur WD, Waibel C, Mach N, Froesch P, Buess M, Bohanes P, Gonzalez M, Alborelli I, Rothschild SI, Koelzer VH, Zippelius A. Tumor immune dynamics and long-term clinical outcome of stage IIIA NSCLC patients treated with neoadjuvant chemoimmunotherapy. Nat Commun. 2025 Sep 30;16(1):8673. doi: 10.1038/s41467-025-63696-5.

  PMID: 41027867 DERIVED

• Rothschild SI, Zippelius A, Eboulet EI, Savic Prince S, Betticher D, Bettini A, Fruh M, Joerger M, Lardinois D, Gelpke H, Mauti LA, Britschgi C, Weder W, Peters S, Mark M, Cathomas R, Ochsenbein AF, Janthur WD, Waibel C, Mach N, Froesch P, Buess M, Bohanes P, Godar G, Rusterholz C, Gonzalez M, Pless M; Swiss Group for Clinical Cancer Research (SAKK). SAKK 16/14: Durvalumab in Addition to Neoadjuvant Chemotherapy in Patients With Stage IIIA(N2) Non-Small-Cell Lung Cancer-A Multicenter Single-Arm Phase II Trial. J Clin Oncol. 2021 Sep 10;39(26):2872-2880. doi: 10.1200/JCO.21.00276. Epub 2021 Jul 12.

  PMID: 34251873 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

durvalumab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Regulatory Affairs
• Organization: Swiss Cancer Institute

regulatory@swisscancerinstitute.ch

+41 31 389 91 91

Study Officials

• Sacha Rothschild, MD, PhD

  University Hospital, Basel, Switzerland

  STUDY CHAIR

Publication Agreements

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

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: October 1, 2015
• First Posted: October 9, 2015
• Study Start: June 16, 2016
• Primary Completion: January 20, 2020
• Study Completion: March 19, 2024
• Last Updated: October 28, 2025
• Results First Posted: October 28, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

CH (19)