A Study of DSP-0509 in Patients With Advanced Solid Tumors to Determine the Safety and the Pharmacokinetic Profile

Summary

Participation Requirements

Description

The primary objective of Part A in the monotherapy arm is to determine the RP2D of DSP-0509 when administered as a single agent. Approximately 21 to 30 patients with advanced solid tumors will be enrolled. At the time of this amendment, 12 patients have been enrolled in the monotherapy cohorts with ...

The primary objective of Part A in the monotherapy arm is to determine the RP2D of DSP-0509 when administered as a single agent. Approximately 21 to 30 patients with advanced solid tumors will be enrolled. At the time of this amendment, 12 patients have been enrolled in the monotherapy cohorts with dose levels of 0.3, 1, and 1.5 mg DSP-0509 given once per week and completed the DLT period. Based on review of DLTs and consistent with the BLRM model, the Safety Review Committee has assessed that continuing at the 1.5 mg dose level is appropriate. Under Protocol Amendment 4, the dose level of 1.5 mg given every two weeks will be applied in Monotherapy Part A. Enrollment of additional cohorts will be based on the dose escalation procedures. The primary objective of Combination Part B is to determine the RP2D of DSP-0509 when administered in combination with pembrolizumab, using a BLRM approach as described above. The combination arm will enroll approximately 21 to 30 patients with advanced solid tumors that are (a) metastatic or unresectable and recurrent, and/or refractory to available therapy, (b) a condition for which pembrolizumab is an approved treatment, and (c) the patients have shown either primary or acquired resistance to an ICI. Under protocol amendment 4, DSP-0509 will be administered on Day 1 and then every 2 weeks thereafter. Pembrolizumab will be initiated on Day 8 and administered using the dose and schedule described (200 mg IV every 3 weeks). To maximize patient safety, enrollment in the first combination escalation cohort will begin at dose level of 0.3 mg DSP-0509 after safety and tolerability of DSP-0509 monotherapy has been confirmed at least 1 dose level higher. The primary objective of Combination Therapy Arm C is to determine preliminary efficacy in the form of the ORR of DSP-0509 when administered in combination with pembrolizumab to an expansion cohort of patients with HNSCC, using a Bayesian Adaptive design approach. Combination Arm C will enroll approximately 20 to 40 patients with HNSCC tumors that are (a) metastatic or unresectable, and recurrent and/or refractory to available therapy, (b) in patients who have been treated with pembrolizumab or other PD-1 or PD-L1 inhibitors in monotherapy, and (c) who have subsequently shown either primary or acquired resistance to ICIs. Dose escalation of DSP-0509 in combination with 400 mg pembrolizumab q6w will start at the same dose of DSP-0509 as the highest (not exceeding the MTD) level tested in the combination regimen with 200 mg pembrolizumab q3w. Upon completion of the DLT evaluation period for the first DSP-0509 dose level tested in combination with 400 mg pembrolizumab q6w in newly enrolled patients, if this dose level is found not to exceed the MTD, any ongoing patients receiving DSP-0509 in combination with pembrolizumab 200 mg q3w will be allowed, at the investigator's discretion, to transition to the 400 mg pembrolizumab q6w regimen, while maintaining the originally assigned DSP-0509 dose level.

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