NCT05383001

Randomized Phase II, Open-label Efficacy and Safety Study of Second-line Durvalumab Plus Tremelimumab Versus Platinum-based Chemotherapy Alone in Patients With NSCLC and First-line Checkpoint-inhibitor Therapy (Re-Check)

Randomized Phase II, Open-label Efficacy and Safety Study of Second-line Durvalumab Plus Tremelimumab Versus Platinum-based Chemotherapy Alone in Patients With NSCLC and First-line Checkpoint-inhibitor Therapy Followed by 2 Cycles of Platinum-based Chemotherapy (Re-Check)

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: AIO-Studien-gGmbH · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is an open label, randomized, Phase II multicenter study designed to evaluate the safety and efficacy of two different second-line strategies: After failure of first line mono-immunotherapy with checkpoint inhibitors (anti-PD-1/PD-L1), and subsequent 2 cycles of standard of care platinum-based chemotherapy, 2 treatment arms will be compared: Arm A (Experimental Arm): After randomization, patients will receive a combination regimen featuring a single, priming dose of tremelimumab together with conventional durvalumab dosing. Durvalumab maintenance therapy will subsequently be continued as study treatment for up to 12 cycles. Arm B: After randomization, patients will continue to receive another 2-4 cycles of platinum-based chemotherapy. Afterwards, patients will end treatment or receive maintenance pemetrexed therapy as per marketing authorization (depending on histology, maximum of 13 cycles) at the discretion of the investigator

Detailed description

Patients without progression after two cycles of chemotherapy (induction treatment phase) will be randomized at a 1:1 ratio into one of 2 treatment arms (combination treatment phase). PD-L1 expression status will be evaluated based on available data. To better focus on patients with expected good clinical benefit from immunomodulating agents, only patients with checkpoint-inhibitor treatment as first-line monotherapy and a progression-free survival of at least 12 weeks will enter the study (at least two re-assessments after initiation of first-line treatment). Consequently, patients with disease progression as best response of first-line therapy cannot enter this study. Directly re-challenging patients with anti-PD-L1 and anti-CTLA agents after disease progression on checkpoint-inhibitor monotherapy will be avoided by the previous application of two cycles of platinum-based chemotherapy as induction treatment, which may also enhance the antigen release from tumor cells and may further support the subsequent immunotherapy.

Conditions

• NSCLC Stage IV

Interventions

Type	Name	Description
DRUG	combination regimen tremelimumab /durvalumab	Induction treatment: 2 cyles of Q3W second-line plantium-based chemotherapy according to standard of care: Cisplatin or carboplatin in combination with pemetrexed, paclitaxel, nab-paclitaxel, vinorelbine or gemcitabine Combination treatment: Durvalumab 1500 mg fixed dose plus tremelimumab 300 mg fixed bolus dose Maintenance Therapy: Durvalumab 1500 mg fixed dose Q4W up to 12 cycles within the study
DRUG	platinum-based chemotherapy (SoC)	Induction treatment: 2 cyles of Q3W second-line plantium-based chemotherapy according to standard of care: Cisplatin or carboplatin in combination with pemetrexed, paclitaxel, nab-paclitaxel, vinorelbine or gemcitabine Combination treatment: Continuation of second-line chemotherapy with 2-4 further cycles (Q3W) platinum-based combination therapy. Maintenance Therapy: Optional continued maintenance therapy with pemetrexed according to marketing authorization will be allowed for a maximum of 13 cycles.

Timeline

• Start date: 2022-05-20
• Primary completion: 2026-05-01
• Completion: 2026-05-01
• First posted: 2022-05-19
• Last updated: 2022-09-27

Locations

1 site across 1 country: Germany