Small Cell Lung Cancer Irinotecan and CDC2-like Kinase Inhibition Trial (SLICK Trial)
Although small cell lung cancer (SCLC) responds dramatically to initial platinum-based chemotherapy, recurrences are nearly universal. The addition of atezolizumab, an immune checkpoint inhibitor, to front-line chemotherapy has recently demonstrated an improvement in overall survival (OS) in extensive stage SCLC (ES-SCLC). Subsequent lines of therapies are associated with modest efficacy in patients with relapsed disease, and the median overall survival is still 12 to 13 months at best. Cirtuvivint is a small molecule inhibitor of the CDC2-like kinases (CLKs) and dual-specificity tyrosine-regulated kinases (DYRKs); inhibiting CLKs and DYRKs has been shown in preclinical models to cause tumor growth inhibition and sensitize cancer cells to cytotoxic chemotherapy. This study is testing the hypothesis that adding cirtuvivint to chemotherapy in patients with relapsed SCLC will be well tolerated and improve the response rate and progression-free survival (PFS).
• Histologically or cytologically confirmed small cell lung cancer that has progressed on at least one line of prior platinum-based chemotherapy, given with or without anti-PD-(L)1 therapy.
• Presence of measurable disease per RECIST 1.1 criteria
• At least 18 years of age.
• ECOG performance status ≤ 2
• Adequate bone marrow and organ function as defined below:
‣ Absolute neutrophil count ≥ 1.0 K/cumm
⁃ Platelets ≥ 100 K/cumm
⁃ Total bilirubin ≤ 1.5 x IULN
⁃ AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN (≤ 5 x IULN for patients with liver metastases)
⁃ Calculated creatinine clearance \> 35 mL/min by Cockcroft-Gault
• The effects of cirtuvivint on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 31 weeks after completion of study treatment (either drug). Should a woman become pregnant or suspect she is pregnant while participating in this study or should a man suspect he has fathered a child, s/he must inform the treating physician immediately.
• Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.