Stage III NSCLC
Conditions
Keywords
Non small cell lung cancer, Unresectable stage III NSCLC
Brief summary
This is a multi-center, open-label, randomized Phase 2 trial evaluating PDR001 in two arms for concurrent chemoradiation and consolidation in the treatment-naïve patients with locally advanced, unresectable stage III NSCLC. Patients will be randomized in a 1:1 ratio (arm A and arm B): * Arm A (consolidation only arm) will be treated with standard platinum-based concurrent chemoradiotherapy, followed by consolidation with PDR001 regimen. * Arm B (concurrent arm) will be treated with PDR001 concurrent with standard platinum-based chemoradiation, followed by consolidation with PDR001 regimen.
Interventions
DRUGstandard platinum-based concurrent chemoradiotherapy, followed by consolidation with PDR001
drug: standard platinum-based concurrent chemoradiotherapy, followed by consolidation with PDR001 Arm A (consolidation only arm) will be treated with standard platinum-based concurrent chemoradiotherapy, followed by consolidation with PDR001 regimen. --For concurrent chemoradiation therapy, chemotherapeutic agents will follow the one of the two regimens of standard of care Paclitaxel 45 mg/m2 at D1, D8, D15, D22, D29, and D36, IV infusion; Carboplatin AUC 2 at D1, D8, D15, D22, D29, and D36, IV infusion Etoposide 50 mg/m2 D1-5, D29-33,IV infusion; Cisplatin 50 mg/m2 D1, D8, D29, and D36; IV infusion - Concurrent radiation therapy (generally, 60 Gy/30 Fx ±10%) - Consolidation therapy: after 2 weeks after completion of radiation therapy (± 7 days), PDR001 400 mg every 4 weeks, until disease progression or an unacceptable adverse event, maximum 12 months.
DRUGPDR001 concurrent with standard platinum-based chemoradiation, followed by consolidation with PDR001
drug:PDR001 concurrent with standard platinum-based chemoradiation, followed by consolidation with PDR001 Arm B (concurrent arm) will be treated with PDR001 concurrent with standard platinum-based chemoradiation, followed by consolidation with PDR001 regimen. -For concurrent chemoradiation therapy, chemotherapeutic agents will follow one of the two regimens of standard of care Paclitaxel 45 mg/m2 at D1, D8, D15, D22, D29, and D36, IV infusion; Carboplatin AUC 2 at D1, D8, D15, D22, D29, and D36, IV infusion Etoposide 50 mg/m2 D1-5, D29-33,IV infusion; Cisplatin 50 mg/m2 days 1,8,29, and 36; IV infusion - Concurrent PDR001 400mg at D1, D29 - Concurrent radiation therapy (generally, 60 Gy/30 Fx ±10%) - Consolidation therapy: after 4 weeks after last dose of PDR001, PDR001 400 mg every 4 weeks, until disease progression or an unacceptable adverse event, maximum 12 months.
Sponsors
Yonsei University
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with cytologically or histologically proven, locally advanced, treatment-naïve, unresectable, both squamous and non-squamous stage III NSCLC\* (According to AJCC TNM staging 8th edition, IIIB and IIIC diseases are eligible; Inoperable stage IIIA disease without any
Exclusion criteria
is also eligible) 2. Patients with targetable mutations such as EGFR, ALK and ROS1 are also eligible 3. Measurable disease based on RECIST 1.1 as determined by the site. 4. Men and women ≥ 20 years of age 5. A performance status of 0 - 1 on the Eastern Cooperative Oncology Group (ECOG) performance Status 6. Adequate hematologic, renal, and hepatic function as follows: * Absolute Neutrophil Count (ANC), \> 1,000/mm3 * Platelets \> 100,000/mm3 * Hemoglobin \> 9.0 g/dL * Serum creatinine \< 1.5 × upper normal limit (ULN) OR creatinine clearance \> 45 mL/min/1.73m2 * AST and/or ALT \< 2.5 × the ULN * Bilirubin \< 1.5 × the ULN 7. 12-Lead electrocardiogram (ECG) shows QTc interval ≤470 msec and without history of Torsades de Pointes or other symptomatic QTc abnormality 8. Written (signed) Informed Consent to participate in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free survival (PFS) | Repeated tumor imaging will be performed every 8 weeks from randomization until the date of disease progression or up to 18 months. And Tumor Imaging Change will assessed by RECIST 1.1 | To compare the progression free survival (PFS) in concurrent plus consolidation PDR001 vs. consolidation PDR001 only in addition to standard platinum-based concurrent chemoradiation, in the patients with locally advanced, unresectable stage III NSCLC. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate antitumor efficacy of PDR001: OS | Repeated tumor imaging will be performed every 8 weeks from randomization until the date of disease progression or up to 18 months. And Tumor Imaging Change will assessed by RECIST 1.1 | To evaluate the overall survival (OS) of PDR001 as concurrent plus consolidation versus consolidation only treatment in addition to platinum-based concurrent chemoradiation, in the patients with locally advanced, unresectable stage III NSCLC. |
| To evaluate antitumor efficacy of PDR001: ORR | Repeated tumor imaging will be performed every 8 weeks from randomization until the date of disease progression or up to 18 months. And Tumor Imaging Change will assessed by RECIST 1.1 | To compare objective response rate (ORR; evaluated by RECIST) of the patients who received platinum-based concurrent chemoradiation with or without concurrent PDR001. |
| Incidence of Treatment-Emergent Adverse Events[Safety and Tolerability) | Repeated tumor imaging will be performed every 8 weeks from randomization until the date of disease progression or up to 18 months. And Tumor Imaging Change will assessed by RECIST 1.1 | To evaluate the safety and tolerability profile of PDR001 as concurrent plus consolidation versus consolidation only treatment in addition to platinum-based concurrent chemoradiation. |
Countries
South Korea
Outcome results
None listed