NCT04125719

PVSRIPO in Combination With Nivolumab in Melanoma

A Phase IB Trial of PVSRIPO in Combination With Nivolumab in Patients With Recurrent PD-1 Refractory Melanoma

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Darell Bigner · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

In this study, patients with metastatic melanoma who have at least one injectable lesion that has been refractory to PD-1 therapy (n=30 patients) will be enrolled. Cohort 1 will include 15 patients who progressed within 3 months (primary resistance) of starting PD-1 therapy and cohort 2 will be patients who progressed after at least 3 months of PD-1 therapy. Patients will receive up to 7 injections of PVSRIPO intra-lesionally in combination with Nivolumab. Nivolumab will be administered according to the FDA-approved dosing schedule of 480 mg intravenously every 4 weeks, beginning \~10 days after the first PVSRIPO infusion and will continue for 4 cycles. Nivolumab may be continued up to 2 years per standard of care after the completion of the PVSRIPO injections.

Detailed description

Patients must have histologically proven unresectable melanoma, stage IIIB, IIIC, IIID, or stage IV (AJCC staging must be documented in patient's medical record, as determined by CT of the chest, abdomen and pelvis, and/or whole body PET scan, and MRI of the brain within 4 weeks prior to administration of study drug). Patients must have failed PD-1 therapy as judged by the treating physician. Patients will initially receive one injection of PVSRIPO intra-lesionally. Based on a phase 1 study of the agent in adult patients with recurrent GBM, the starting amount to be delivered will be 1x108 tissue culture infectious dose (TCID50) prior to initiation of nivolumab. Nivolumab will be administered according to the FDA-approved dosing schedule of 480 mg intravenously every 4 weeks, beginning \~10 days after the first PVSRIPO infusion and will continue for 4 cycles. PVSRIPO will then be given intralesionally to multiple lesions (if present) at days 38, 66, and 94. At Day 108 after 4 doses of nivolumab and 4 treatments of PVSRIPO, imaging and a full disease assessment will be done and iRECIST determined. A patient with complete response (CR) or a partial response (PR) (at least at 75% decrease in the sum of all diameters of all target lesions plus new lesions) will continue on nivolumab for up to 2 years. For patients with PR (\< 75% decrease), stable disease (SD), or progressive disease (PD), an additional 3 treatments of PVSRIPO q4weeks can be given concurrently with 3 doses of monthly nivolumab. The lesions will be chosen at discretion of principal investigator (PI) and can be new lesions, previously injected lesions, or untreated lesions. At Day 234 (±7 days), (after 7 total PVSRIPO injections and 8 doses of nivolumab), patients with PD will be off study, any patient with CR, PR, SD can receive up to 2 years total of nivolumab. If a patient has no remaining injectable lesions at any point during the study, PVSRIPO will not be given, but patients can continue on nivolumab.

Conditions

• Melanoma

Interventions

Type	Name	Description
BIOLOGICAL	PVSRIPO	Intralesional injection of PVSRIPO
DRUG	Nivolumab	Nivolumab infusion

Timeline

• Start date: 2020-06-01
• Primary completion: 2024-10-01
• Completion: 2024-10-01
• First posted: 2019-10-14
• Last updated: 2020-02-11

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study