Oncology Daily Report: 01/15/2024

ALK-positive crizotinib-resistant NSCLC

A phase I human radiolabeled mass balance study investigated the effect of iruplinalkib (WX-0593) in healthy subjects and found that iruplinalkib was absorbed quickly and eliminated slowly from plasma, with a maximum concentration time (T(max)) of 1.5 hours and a half-life (t(1/2)) of 28.6 hours (1). Approximately 88.85% of iruplinalkib was excreted at 312 hours, including 20.23% in urine and 68.63% in feces. Seventeen metabolites of iruplinalkib were identified, with M3b (demethylation), M7 (cysteine conjugation), M11 (oxidative dehydrogenation and cysteine conjugation of M3b), and M12 (oxidative dehydrogenation and cysteine conjugation) being the prominent metabolites in humans. Iruplinalkib-related compounds were found to be covalently bound to proteins, accounting for 7.70% in plasma and 17.96% in feces. No serious adverse events were observed, indicating iruplinalkib was well tolerated at the study dose.

Reference

Bian Y, Ma S, Yao Q, Hu T, Ge M, Li H, Zheng S, Gu Z, Feng H, Yu Z, Huang C, Zhang H, Zhao L, Miao L. Pharmacokinetics, metabolism, excretion and safety of iruplinalkib (WX-0593), a Novel ALK Inhibitor, in healthy subjects: a phase I human radiolabeled Mass balance study. Expert Opin Investig Drugs. 2024 Jan 15. doi: 10.1080/13543784.2024.2305134. Epub ahead of print. PMID: 38224050.

Resectable Pancreatic Ductal Adenocarcinoma

A phase 2 randomized study investigated the effect of neoadjuvant FOLFIRINOX (oxaliplatin, irinotecan, leucovorin, and fluorouracil) in 140 patients with resectable pancreatic head cancer and found that the proportion of patients alive at 18 months was 60% (95% CI 49-71) in the neoadjuvant FOLFIRINOX group versus 73% (62-84) in the upfront surgery group (p=0·032) (1). The median overall survival was 25.1 months (95% CI 17.2-34.9) in the neoadjuvant group versus 38.5 months (27.6-not reached) in the upfront surgery group (hazard ratio [HR] 1.52 [95% CI 1.00-2.33], log-rank p=0.050). The study did not show a survival benefit from neoadjuvant FOLFIRINOX compared with upfront surgery. This study was part of the NORPACT-1 trial.

Reference

Labori KJ, Bratlie SO, Andersson B, Angelsen JH, Biörserud C, Björnsson B, Bringeland EA, Elander N, Garresori H, Grønbech JE, Haux J, Hemmingsson O, Liljefors MG, Myklebust TÅ, Nymo LS, Peltola K, Pfeiffer P, Sallinen V, Sandström P, Sparrelid E, Stenvold H, Søreide K, Tingstedt B, Verbeke C, Öhlund D, Klint L, Dueland S, Lassen K; Nordic Pancreatic Cancer Trial-1 study group. Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1): a multicentre, randomised, phase 2 trial. Lancet Gastroenterol Hepatol. 2024 Jan 15:S2468-1253(23)00405-3. doi: 10.1016/S2468-1253(23)00405-3. Epub ahead of print. PMID: 38237621.

Advanced Neuroendocrine Tumors and Neuroendocrine Carcinomas

A Phase II Open-Label, Single-Arm, Multi-Cohort study investigated the effect of Surufatinib plus Toripalimab in 40 patients with advanced neuroendocrine tumors (NETs) or neuroendocrine carcinomas (NECs) or mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) who had failed or were intolerable of standard treatment (1). The study found objective response rates (ORRs) of 21.1% (95% CI: 6.1-45.6) in the NET cohort (n=19) and 23.8% (95% CI: 8.2-47.2) in the NEC-MiNEN cohort (n=21). Median duration of response (DoR) was 7.1 months (6.9-not evaluable [NE]) for NETs and 4.1 months (3.0-NE) for NEC-MiNENs. Median progression-free survival (PFS) was 9.6 months (4.1-NE) for NETs and 4.1 months (1.5-5.5) for NEC-MiNENs; median overall survival (OS) was 27.3 months (15.3-NE) for NETs and 10.9 months (9.1-14.6) for NEC-MiNENs. Grade ≥ 3 treatment-related adverse events occurred in 18 (45.0%) patients. The study concluded that Surufatinib plus Toripalimab showed antitumor activity and a tolerable safety profile in patients with previously treated NETs/NECs/MiNENs. Further study of this combination regimen is ongoing for advanced NECs, for which current therapeutic options remain limited. ClinicalTrials.gov identifier: NCT04169672.

Reference

Zhang P, Shi S, Xu J, Chen Z, Song L, Zhang X, Cheng Y, Zhang Y, Ye F, Li Z, Yin F, Ji D, Gao H, Li Y, Chen W, Yang M, Weng D, Wu C, Ma Y, Sheng W, Zhao Y, Yin X, Shen W, Su W, Shi M, Fan S, Tan P, Xu Q, Lu M, Shen L. Surufatinib plus toripalimab in patients with advanced neuroendocrine tumours and neuroendocrine carcinomas: An open-label, single-arm, multi-cohort phase II trial. Eur J Cancer. 2024 Jan 15;199:113539. doi: 10.1016/j.ejca.2024.113539. Epub ahead of print. PMID: 38237373.