WCLC 2025 - Posters & ePosters-EP.13.40 Trial of Chemotherapy in Patients With Relapsed Small Cell Lung Cancer Combined With Allopurinol and Mycophenolate (CLAMP)

EP.13.40 Trial of Chemotherapy in Patients With Relapsed Small Cell Lung Cancer Combined With Allopurinol and Mycophenolate (CLAMP)

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This study evaluates the safety and efficacy of combining chemotherapy (irinotecan) with mycophenolate mofetil (MMF) and allopurinol (CLAMP regimen) in patients with relapsed small cell lung cancer (SCLC), a disease with poor prognosis following first-line therapy. Relapsed SCLC often exhibits resistance linked to MYC amplification, which promotes purine synthesis through inosine monophosphate dehydrogenase (IMPDH) upregulation. MMF inhibits purine synthesis, and allopurinol limits purine salvage pathways, potentially overcoming this resistance mechanism.<br /><br />The phase I/II open-label, single-center trial enrolled 17 patients (median age 63) with relapsed SCLC who had progressed on prior platinum-based therapy and immunotherapy. The study aimed to assess safety, dose-limiting toxicities (DLTs), overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) of the combination.<br /><br />Results showed that no DLTs occurred at the initial irinotecan dose level (DL1), although several patients required dose reductions or discontinued therapy. Two DLTs were observed at a lower dose level (DL0). Treatment-related adverse events (TRAE) were frequent, with 100% experiencing at least one, mainly anemia and diarrhea, and 29% discontinuing due to toxicity. Importantly, an ORR of 41% (6 partial responses, 1 complete response) and a disease control rate of 71% were observed, indicating a potential efficacy signal. Median follow-up was 7.3 months. Most patients received subsequent systemic therapies.<br /><br />The study concluded that while the MMF, allopurinol, and irinotecan combination showed promising activity, increased toxicities limited its tolerability, leading to early closure of accrual at the lowest dose. The authors suggest that combining MMF and allopurinol with other novel agents with different side effect profiles warrants further investigation to improve outcomes in relapsed SCLC.

Asset Subtitle

Brendan Knapp

Meta Tag

Speaker Brendan Knapp

Topic Small Cell Lung Cancer and Neuroendocrine Tumors

Keywords

small cell lung cancer

SCLC

relapsed SCLC

chemotherapy

irinotecan

mycophenolate mofetil

MMF

allopurinol

CLAMP regimen

MYC amplification