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.
Despite multimodal therapy, the cure rate of patients with stage IIIA NSCLC is poor and therapy outcome failed to improve during the past years. The addition of immunotherapy with the anti-PD-L1 antibody MEDI4736 as a novel treatment modality has the potential to improve the outcome without adding substantial toxicity to an otherwise intensive multimodality treatment, as MEDI4736 has been generally well tolerated. Based on the current evidence on immune checkpoint inhibition, there is a strong rationale to test this novel treatment modality also in the curative setting in order to improve local tumor control and prevent distant metastasis to improve the cure rate in this patient population. The trial investigates the addition of pre- and post-operative immune checkpoint inhibition with MEDI4736 to the previously established standard of care for stage IIIA(N2) patients, which is based on the trials SAKK16/96 and SAKK16/00. Patients whose tumor is deemed resectable at diagnosis will receive 3 cycles (21 days each) of standard chemotherapy with cisplatin (100 mg/m2) / docetaxel (85 mg/m2), 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
68
fixed dosing 750 mg
Stadtspital Triemli
Zurich, Canton of Zurich, Switzerland
Kantonsspital Aarau
Aarau, Switzerland
Event-free Survival (EFS) Rate
Measured using the Kaplan-Meier method
Time frame: at 12 months
Median Event-free Survival (EFS)
Measured using the Kaplan-Meier method
Time frame: up to 7 years from registration
Overall Survival (OS) Rate
Measured using the Kaplan-Meier method
Time frame: at 1, 2, 3, 4 & 5 years after registration
Objective Response (OR) After Neoadjuvant Chemotherapy (FAS)
Time frame: After Neoadjuvant Chemotherapy, up to 3 months
Objective Response (OR) After Neoadjuvant Immunotherapy (FAS II)
Measured using the Kaplan-Meier method
Time frame: After Neoadjuvant immunotherapy, up to 3 months
Pathological Responses (pCR)
Time frame: at 12 months
Adverse Events (AEs) (According to NCI CTCAE v4.0)
Outcomes are described under "Adverse events".
Time frame: Adverse events were recorded from registration up to 13 months after surgery, up to 17 months. Deaths were reported up to 8 years from registration
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