Ph I/II Trial of Systemic VSV-IFNβ-NIS in Combination With Checkpoint Inhibitor Therapy in Patients With Select Solid Tumors

Solid Tumor Clinical Trial

Official title: Phase 1-2 Trial of Systemically Administered VSV-IFNβ-NIS in Combination With Checkpoint Inhibitor Therapy in Patients With Selected Solid Tumors

Status Recruiting

Clinical Trial Summary

The safety run-in portion of this study is designed to identify the optimal dose of VSV-IFNβ-NIS in combination with pembrolizumab in patients with solid tumors and follows the 3+3 design. The expansion portion will use one-sample binomial designs to assess the efficacy of the combination in patients with refractory NSCLC or NEC. The optimal dose (RP2D) determined in the dose escalation portion of the trial will be used for the expansion portion. The study has been conducted with a dose of 1.7 × 1010 as the recommended phase II dose in an expansion cohort of 10 patients with NSCLC. However, current data suggests that VSV-IFNβ-NIS doses of up to 1.7 × 1011 is safe and likely more efficacious. Thus, this study will test a second VSV-IFNβ-NIS dose level, 1.0x1011 TCID50. A safety assessment will be carried out after 3 patients are enrolled. If this dose schedule is well tolerated and virus PK are not negatively impacted, both the NSCLC and NEC expansion cohorts will open using this dose schedule. If 2 of the first 3 patients or 2 of the first 6 patients experience a DLT, the dose will be de-escalated to 5 x 1010. The safety run-in/dose escalation portion of this study is expected to require a minimum of 3 patients and a maximum of 18 patients (6 patients per dose level). The expansion portion of this study is expected to require a minimum of 10 per cohort. The NSCLC and NEC patients enrolled at the identified optimal dose in the dose escalation cohort would be included in the dose expansion cohort if they are evaluable for the primary endpoint in the expansion portion (4 dose escalation patients at the optimal dose are expected to roll over to the expansion). Therefore, the overall sample size will be a maximum of 40 patients.

Clinical Trial Description

All patients will be dosed with VSV-IFNβ-NIS on day 1. For Part A, Part B [Group 1], and Part C [Group 1] pembrolizumab will be administered on day 1 (concurrent pembrolizumab dosing). For Part A, and Parts B and C [Group 2] pembrolizumab may be administered on day 8 (delayed pembrolizumab dosing). pembrolizumab treatment will continue Q3W per the Keytruda® USPI, with efficacy evaluations after cycle 2 then every 9 weeks until PD. ;

Related Conditions & MeSH terms

• Carcinoma, Neuroendocrine
• Neuroendocrine Carcinoma
• Non Small Cell Lung Cancer
• Solid Tumor

• NCT number: NCT03647163
• Study type: Interventional
• Source: Vyriad, Inc.
• Contact: Jennifer Boughton
• Phone: 9085533135
• Email: JBoughton@vyriad.com
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 9, 2019
• Completion date: December 1, 2024