Phase I Dose-Escalation Study of SCB01A, a Microtubule Inhibitor with Vascular Disrupting Activity, in Patients with Advanced Solid Tumors.

Abstract

LESSONS LEARNED:

SCB01A is a novel microtubule inhibitor with vascular disrupting activity. This first-in-human study demonstrated SCB01A safety, pharmacokinetics, and preliminary antitumor activity. SCB01A is safe and well tolerated in patients with advanced solid malignancies with manageable neurotoxicity.

BACKGROUND:

SCB01A, a novel microtubule inhibitor, has vascular disrupting activity.

METHODS:

In this phase I dose-escalation and extension study, patients with advanced solid tumors were administered intravenous SCB01A infusions for 3 hours once every 21 days. Rapid titration and a 3 + 3 design escalated the dose from 2 mg/m2 to the maximum tolerated dose (MTD) based on dose-limiting toxicity (DLT). SCB01A-induced cellular neurotoxicity was evaluated in dorsal root ganglion cells. The primary endpoint was MTD. Safety, pharmacokinetics (PK), and tumor response were secondary endpoints.

RESULTS:

Treatment-related adverse events included anemia, nausea, vomiting, fatigue, fever, and peripheral sensorimotor neuropathy. DLTs included grade 4 elevated creatine phosphokinase (CPK) in the 4 mg/m2 cohort; grade 3 gastric hemorrhage in the 6.5 mg/m2 cohort; grade 2 thromboembolic event in the 24 mg/m2 cohort; and grade 3 peripheral sensorimotor neuropathy, grade 3 elevated aspartate aminotransferase, and grade 3 hypertension in the 32 mg/m2 cohort. The MTD was 24 mg/m2 , and average half-life was ~2.5 hours. The area under the curve-dose response relationship was linear. Nineteen subjects were stable after two cycles. The longest treatment lasted 24 cycles. SCB01A-induced neurotoxicity was reversible in vitro.

CONCLUSION:

The MTD of SCB01A was 24 mg/m2 every 21 days; it is safe and tolerable in patients with solid tumors.

• Authors: Her-Shyong Shiah, Nai-Jung Chiang, Chia-Chi Lin, Chia-Jui Yen, Hui-Jen Tsai, Shang-Yin Wu, Wu-Chou Su, Kwang-Yu Chang, Ching-Chiung Wang, Jang-Yang Chang, Li-Tzong Chen
• Journal: The oncologist (Oncologist) Vol. 26 Issue 4 Pg. e567-e579 (04 2021) ISSN: 1549-490X [Electronic] England
• PMID: 33245172 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © AlphaMed Press; the data published online to support this summary are the property of the authors.

Chemical References

• Antineoplastic Agents
• Tubulin Modulators

Topics

• Antineoplastic Agents (adverse effects)
• Dose-Response Relationship, Drug
• Humans
• Maximum Tolerated Dose
• Microtubules
• Neoplasms (drug therapy)
• Treatment Outcome
• Tubulin Modulators