Background and Aims: This study aimed to investigate safety and efficacy of silmitasertib, an oral small molecule casein kinase 2 inhibitor, plus gemcitabine and cisplatin (G+C) versus G+C in locally advanced/metastatic cholangiocarcinoma. Approach and Results: This work is a Phase 1b/2 study (S4-13-001). In Phase 2, patients received silmitasertib 1000 mg twice daily for 10 days with G+C on Days 1 and 8 of a 21-day cycle. Primary efficacy endpoint was progression-free survival (PFS) in the modified intent-to-treat population (defined as patients who completed at least one cycle of silmitasertib without dose interruption/reduction) from both phases (silmitasertib/G+C n = 55, G+C n = 29). The response was assessed by Response Evaluation Criteria in Solid Tumors v1.1. The median PFS was 11.2 months (95% confidence interval [CI], 7.6, 14.7) versus 5.8 months (95% CI, 3.1, not evaluable [NE]) (p = 0.0496); 10-month PFS was 56.1% (95% CI, 38.8%, 70.2%) versus 22.2% (95% CI, 1.8%, 56.7%); and median overall survival was 17.4 months (95% CI, 13.4, 25.7) versus 14.9 months (95% CI, 9.9, NE) with silmitasertib/G+C versus G+C. Overall response rate was 34.0% versus 30.8%; the disease control rate was 86.0% versus 88.5% with silmitasertib/G+C versus G+C. Almost all silmitasertib/G+C (99%) and G+C (93%) patients reported at least one treatment emergent adverse event (TEAE). The most common TEAEs (all grades) with silmitasertib/G+C versus G+C were diarrhea (70% versus 13%), nausea (59% vs. 30%), fatigue (47% vs. 47%), vomiting (39% vs. 7%), and anemia (39% vs. 30%). Twelve patients (10%) discontinued treatment because of TEAEs during the study. Conclusions: Silmitasertib/G+C demonstrated promising preliminary evidence of efficacy for the first-line treatment of patients with locally advanced/metastatic cholangiocarcinoma.
|Number of pages||14|
|Publication status||Published - 2023 Mar|
Bibliographical noteFunding Information:
Mitesh J. Borad consults for ADC Therapeutics, Exelixis, G1 Therapeutics, HUYA, Genentech, Immunovative, Inspyr, Lynx Group, Merck, OncBioMune, and Western Oncolytics. He received grants from Adaptimmune, Agios, ARIAD, Astra Zeneca, Basilea, Bioline, Boston Biomed, Celgene, Dicerna, EMD Serono, Halozyme, Incyte, Isis Pharmaceuticals, Medimmune, Mirna, Novartis, PUMA, Sun Biopharmacueticals, Senhwa Pharmaceuticals, QED, Redhill, Sillajen, Taiho, and Toray. Kabir Mody owns stock in and is employed by IMV, Inc. He owns stock in and advises CytoDyn, Inc. He consults for AstraZeneca, Ipsen, Genentech, BTG, Boston Scientific, Incyte, QED, and Taiho. Joleen Hubbard advises and received grants from Bayer, Merck, and Incyte. She advises BeiGene. She received grants from Boston Biomedical, Senhwa Pharmaceuticals, TriOncology, Seattle Genetics, Hutchison MediPharma, Pionyr Immunotherapeutics, Trovogene, G1 Therapeutics, Roche, and Treos Bio. John Soong owns stock in and is employed by Senhwa Biosciences. Daniel McCormick is employed by Senhwa Biosciences. Emmett Tse is employed by Senhwa Biosciences. Ahmad Bayat is employed by and has other interests in Amarex Clinical Research. Daniel Ahn owns stock in Natera. He consults for Eisai, Genentech, Exelixis, Novartis, and Advanced Accelerator Applications. S. Lindsey Davis advises Genentech. Joon Oh Park consults for and received grants from BMS and Servier. He advises and received grants from MedPacto. He consults for AstraZeneca. He advises MediRama. He received grants from ABL Bio. Do‐Youn Oh advises and received grants from AstraZeneca and Novartis. She received grants from Genentech/Roche, Merck, Serono, Bayer, Taiho, and ASLAN. She received grants from Array, Eli Lilly, Servier, BeiGene, MSD, and Handa.
We thank all the patients who participated in this study, the patients’ families, Dr Carlos Becerra, the clinical investigators, clinical research nurses, clinical research monitors, data management team, and all other members of the S4‐13‐001 clinical study team. We also thank Lee Miller and Kevin De‐Voy from Miller Medical Communications for their medical editing/writing assistance, which was funded by Senhwa Biosciences Corporation.
Supported by Senhwa Biosciences.
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