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Updated: Dec 17, 2025
Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer
Published on: February 12, 2017
Biomarker-driven phase 2 umbrella trial study for patients with recurrent small cell lung cancer failing
Sehhoon Park1, Joonho Shim2,3, Peter G S Mortimer4
1Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Background:
A high percentage of small cell lung cancer (SCLC) cases harbor cell cycle-related gene mutations and RICTOR amplification. Based on underlying somatic mutations, the authors have conducted a phase 2 biomarker-driven, multiarm umbrella study.
Methods:
The SCLC Umbrella Korea StudiES (SUKSES) is an adaptive platform trial that undergoes continual modification according to the observed outcomes. This study included 286 patients with SCLC who failed platinum therapy and who had known genomic profiles based on a predesigned screening trial. Patients with MYC amplification or CDKN2A and TP53 co-alterations were allocated to adavosertib (SUKSES protocol C [SUKSES-C]; 7 patients) and those with RICTOR amplification were allocated to vistusertib (SUKSES-D; 4 patients). Alternatively, patients who were without any predefined biomarkers were assigned to a non-biomarker-selected arm: adavosertib (SUKSES-N1; 21 patients) or AZD2811NP (SUKSES-N3; 15 patients).
Results:
Patients in the SUKSES-C and SUKSES-N1 arms demonstrated no objective response. Three patients presented with stable disease (SD) in SUKSES-C and 6 patients in SUKSES-N1. The median progression-free survival (PFS) was 1.3 months (95% confidence interval, 0.9 months to not available) for SUKSES-C and 1.2 months (95% CI, 1.1-1.4 months) for SUKSES-N1. Patients in the SUKSES-D arm demonstrated no objective response and no SD, with a PFS of 1.2 months (95% CI, 1.0 months to not available). The SUKSES-N3 arm had 5 patients with SD and a PFS of 1.6 months (95% CI, 0.9-1.7 months), without an objective response. Grade≥3 adverse events (graded according to National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.03]) were observed as follows: 3.2% in the SUKSES-C and SUKSES-N1 arms and 50.0% in the SUKSES-D arm. Target-related neutropenia (grade≥3) was observed in approximately 60.0% of patients in the AZD2811NP arm using the current dosing schedule.
Conclusions:
To the best of the authors' knowledge, the current study is the first biomarker-driven umbrella study conducted in patients with recurrent SCLC. Although the current study demonstrated the limited clinical efficacy of monotherapy, novel biomarker approaches using other cell cycle inhibitor(s) or combinations warrant further investigation.
Insights
This study found limited efficacy for targeted therapies in small cell lung cancer (SCLC) patients, with no objective responses observed in most arms. Further research into novel biomarker strategies and combination therapies is warranted for recurrent SCLC.
Area of Science:
- Oncology
- Genomics
- Clinical Trials
Background:
- Small cell lung cancer (SCLC) frequently exhibits cell cycle gene mutations and RICTOR amplification.
- Somatic mutations guide treatment selection in SCLC, necessitating biomarker-driven approaches.
Purpose of the Study:
- To evaluate the efficacy of targeted therapies in patients with recurrent SCLC based on specific genomic alterations.
- To conduct a phase 2 biomarker-driven, multiarm umbrella study (SCLC Umbrella Korea StudiES - SUKSES) for SCLC.
Main Methods:
- An adaptive platform trial enrolled 286 SCLC patients post-platinum therapy with known genomic profiles.
- Patients were assigned to adavosertib or vistusertib based on specific biomarkers (MYC, CDKN2A/TP53, RICTOR amplifications).
- Non-biomarker-selected arms received adavosertib or AZD2811NP.
Main Results:
- No objective responses were observed in adavosertib (SUKSES-C, SUKSES-N1) or vistusertib (SUKSES-D) arms.
- Stable disease (SD) was observed in some patients across arms, with median progression-free survival (PFS) generally below 2 months.
- High-grade adverse events were noted, particularly neutropenia in the AZD2811NP arm (60%).
Conclusions:
- The study represents the first biomarker-driven umbrella trial for recurrent SCLC.
- Monotherapy demonstrated limited clinical efficacy, highlighting the need for novel biomarker strategies.
- Combination therapies or alternative cell cycle inhibitors warrant further investigation for SCLC treatment.
