NCT04572451

Safety of SBRT With Anti-PD1 and Anti-IL-8 for the Treatment of Multiple Metastases in Advanced Solid Tumors and Melanoma

Phase I Study Investigating the Safety of Stereotactic Body Radiotherapy (SBRT) With Anti-PD1 and Anti-IL-8 for the Treatment of Multiple Metastases in Advanced Solid Tumors and Melanoma

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: Yana Najjar · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Nivolumab (and other agents affecting the anti-programmed death-1 \[anti-PD-1\] pathway) have demonstrated anti-tumor activity in multiple tumor types. Combinations of immune-oncology (IO) agents with complimentary mechanisms as well as radiation represent a promising strategy to improve response rates to immunotherapy and overcome resistance. In this phase I/Ib study, radiation will be used in combination with IO agents nivolumab and anti-IL-8 (BMS-986253) to assess toxicity by organ system and then assess the preliminary efficacy of the treatment regimen. In Part 1, the study will determine the safe doses of radiation by organ site in conjunction with nivolumab and BMS-986253. In Part 2, the treatment regimen will be investigated in melanoma, prioritizing acral melanoma, to describe the response rate to treatment as well as other clinical and safety outcomes. The study will also provide the opportunity to evaluate changes in the tumor microenvironment induced by the treatment.

Detailed description

This is a study of SBRT in combination with nivolumab and BMS-986253, a monoclonal antibody (mAb) against human interleukin-8 (IL-8), conducted in humans with advanced solid tumors. This study will evaluate the safety profile, tolerability and preliminary efficacy of SBRT in combination with BMS-986253 and nivolumab in participants with advanced solid tumors and then specifically in melanoma, focused on acral melanoma. The study will be conducted in 2 parts. Part 1 will evaluate the safety, tolerability of different doses of SBRT in combination with nivolumab (480 mg) and BMS-986253 (2400mg) every 2 weeks (Q2W) in participants with advanced solid tumors. This phase will begin with a cohort of participants who will receive a 2,400 mg flat dose of BMS-986253 Q2W combined with 480 mg flat dose of nivolumab Q4W along with SBRT (the dose is dependent on the irradiating organ). Part 2 will assess preliminary efficacy of SBRT in combination with nivolumab and BMS-986253 in participants with advanced/metastatic/unresectable melanoma, focusing on acral melanoma, who progressed on anti-PD-(L)1 therapy. This study aims to determine that safe doses will be found using ablative doses of SBRT with concurrent IO agents. Additional safety, tolerability and preliminary efficacy information in specific patient population will be gathered. Twenty participants with anti-PD-(L)1 refractory advanced/unresectable/metastatic melanoma, focusing on acral melanoma, will be enrolled into efficacy phase. Note: The Sponsor-Investigator/Study Principal Investigator of this trial is Yana Najjar, MD at the University of Pittsburgh/UPMC. The Sponsor-Investigator of this trial at University of Chicago is Steven Chmura MD, PhD

Conditions

• Melanoma
• Unresectable Solid Tumors
• Neoplasms
• Neoplasms by Histologic Type
• Neoplasms by Site
• Antineoplastic Agents, Immunological
• Antineoplastic Agents
• Immune Checkpoint Inhibitors
• Molecular Mechanisms of Pharmacological Action
• Nivolumab

Interventions

Type	Name	Description
DRUG	nivolumab	Nivolumab (BMS-936558-01), 480 mg intravenous (every 4 weeks) Treatment must be within 7 days of the last dose of radiation.
DRUG	BMS-986253	BMS-986253 (Anti-IL-8), 2,400 mg intravenous (every 2 weeks) Treatment must be within 7 days of the last dose of radiation.
RADIATION	Stereotactic Body Radiotherapy (SBRT)	Stereotactic Body Radiotherapy (SBRT) (varying doses) SBRT: Initial Dose fractionation of 3 or 5 fractions of radiation as determined by the location of the metastases to be irradiated, to at least 1 but no more than 4 metastatic lesions. There will be a minimum of 40 hours between treatments for an individual metastasis. SBRT must be completed within a 14-day window, separate from the screening phase. Treatment with nivolumab and BMS-986253 must be within 7 days of the last dose of radiation.

Timeline

• Start date: 2021-11-29
• Primary completion: 2024-05-17
• Completion: 2027-05-31
• First posted: 2020-10-01
• Last updated: 2025-08-01

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study