First-in-human phase I study of SOR-C13, a TRPV6 calcium channel inhibitor, in patients with advanced solid tumors.
Introduction This was an open-label, dose escalation (3 + 3 design), Phase I study of SOR-C13 in patients with advanced tumors of epithelial origin. Primary objectives were to assess safety/tolerability and pharmacokinetics. Secondary goals were to assess pharmacodynamics and efficacy of SOR-C13. Methods SOR-C13 was administered IV QD on days 1-3 and 8-10 of a 21-day cycle. Doses were 2.75 and 5.5 mg/kg (20-min infusion) and 1.375, 2.75, 4.13 and 6.2 mg/kg (90-min infusion). Toxicity was assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Dose limiting toxicity (DLT) was assessed within the first treatment cycle. Tumors were evaluated, using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, after two cycles. Results Twenty-three patients were treated. No drug-related serious adverse events occurred. DLTs occurred in six patients: asymptomatic, drug-related, transient Grade 2 hypocalcemia (4 patients), and unrelated Grade 3 anemia and Grade 3 atrial fibrillation, 1 patient each. Calcium and vitamin D supplementation eliminated further Grade 2 hypocalcemia. One Grade 3 treatment emergent adverse event, urticaria, was definitely related to SOR-C13. Four possibly drug-related, Grade 3 events (alanine aminotransferase and aspartate aminotransferase elevation, headache, and hypokalemia) were observed. Of 22 evaluable patients, 54.5% showed stable disease ranging from 2.8 to 12.5 months. The best response was a 27% reduction in a pancreatic tumor with a 55% reduction in CA19-9 levels at 6.2 mg/kg. Conclusion SOR-C13 was safe and tolerated up to 6.2 mg/kg. The Maximal Tolerated Dose (MTD) was not established. Stable disease suggested antitumor activity.
Department of Investigational Cancer Therapeutics, M. D. Anderson Cancer Center, Houston, TX, USA.
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Fu
Juravinski Cancer Centre, Hamilton, ON, Canada.
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Hirte
London Health Sciences Centre, London, ON, Canada.
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Welch
Soricimed Biopharma Inc., Moncton, NB, Canada.
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Ilenchuk
Soricimed Biopharma Inc., Moncton, NB, Canada.
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Lutes
Soricimed Biopharma Inc., Moncton, NB, Canada.
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Rice
Sagecon Inc., Oakville, ON, Canada.
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Fields
CLINSIG Research Consulting Inc., Brampton, ON, Canada.
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Nemet
Soricimed Biopharma Inc., Moncton, NB, Canada.
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Dugourd
Department of Investigational Cancer Therapeutics, M. D. Anderson Cancer Center, Houston, TX, USA.
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Piha-Paul
Department of Investigational Cancer Therapeutics, M. D. Anderson Cancer Center, Houston, TX, USA.
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Subbiah
Department of Investigational Cancer Therapeutics, M. D. Anderson Cancer Center, Houston, TX, USA.
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Liu
Department of Investigational Cancer Therapeutics, M. D. Anderson Cancer Center, Houston, TX, USA.
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J
Gong
Department of Investigational Cancer Therapeutics, M. D. Anderson Cancer Center, Houston, TX, USA.
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Hong
Soricimed Biopharma Inc., Moncton, NB, Canada. jstewart@soricimed.com.
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Stewart
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D015220:Calcium Channels / Q000235:genetics; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D006996:Hypocalcemia / Q000139:chemically induced; D007008:Hypokalemia / Q000139:chemically induced; D053538:Keratin-18 / Q000097:blood; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010455:Peptides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000097:blood; D050916:TRPV Cation Channels / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D014581:Urticaria / Q000139:chemically induced
D000970:Antineoplastic Agents; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D053538:Keratin-18; D010455:Peptides; D012333:RNA, Messenger; C000626599:SOR-C13; D050916:TRPV Cation Channels; C422827:TRPV6 protein, human; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
Calcium channel; Oncology; Sor-C13; TRPV6