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

NCT04572451 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: HCC 20-228
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief 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.

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

Keywords

Anti-PD-1 monoclonal antibody (mAb); Anti-IL-8; Stereotactic Body Radiotherapy (SBRT)

Outcome Measures

Primary Outcomes (1)

• Rate of Dose Limiting Toxicities (DLT)

  The rate of Dose Limiting Toxicities (DLT) that are determined to be definitely, probably or possibly attributed to SBRT or one or both of the immunotherapies. Patients receiving one of more fractions of SBRT are evaluable for DLT. Toxicities include grade 3 or higher adverse events, by organ system, by Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

  Up to 8 weeks after start of immunotherapeutic treatment

Secondary Outcomes (6)

• Incidence of grade 3 or higher adverse events

  Up to 1 year after start of immunotherapeutic treatment

• Objective Response

  Up to 3 years

• Progression-free survival (PFS)

  Up to 3 years

• Overall survival (OS)

  Up to 3 years

• Local tumor control (RECIST v1.1)

  Up to 3 years

Study Arms (1)

Nivolumab (Anti-PD-1) + BMS-986253 (Anti-IL-8) + SBRT

EXPERIMENTAL

480 mg intravenous nivolumab (BMS-936558-01) every 4 weeks + 2,400 mg intravenous BMS-986253 (Anti-IL-8) every 2 weeks + Stereotactic Body Radiotherapy (SBRT)

Drug: nivolumab; Drug: BMS-986253; Radiation: Stereotactic Body Radiotherapy (SBRT)

Interventions

nivolumab DRUG

Nivolumab (BMS-936558-01), 480 mg intravenous (every 4 weeks) Treatment must be within 7 days of the last dose of radiation.

Also known as: Opdivo®, Anti-PD-1

Nivolumab (Anti-PD-1) + BMS-986253 (Anti-IL-8) + SBRT

BMS-986253 DRUG

BMS-986253 (Anti-IL-8), 2,400 mg intravenous (every 2 weeks) Treatment must be within 7 days of the last dose of radiation.

Also known as: Anti-IL-8

Nivolumab (Anti-PD-1) + BMS-986253 (Anti-IL-8) + SBRT

Stereotactic Body Radiotherapy (SBRT) RADIATION

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.

Nivolumab (Anti-PD-1) + BMS-986253 (Anti-IL-8) + SBRT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• SAFETY COHORT
• Patients with advanced/metastatic/unresectable solid tumors progressed on standard therapies. Patients with melanoma and RCC will make up approximately 30% of total cohort.
• Patients with 1-4 tumor sites that can be irradiated safely
• Age \> or equal 18 years
• ECOG performance status 0 or 1
• Patients must have normal organ and marrow function as defined below:
• Leukocytes ≥ 3000/mcL;
• absolute neutrophil count ≥ 1500/mcL;
• Platelets ≥ 100,000/mcL;
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × upper limit of normal (ULN) ;
• Total bilirubin ≤ 1.5 × ULN (except participants with Gilbert's Syndrome who must have normal direct bilirubin)
• Serum creatinine ≤ 1.5 × ULN Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non- nodal lesions and short axis for nodal lesions) as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam
• Ability to understand and the willingness to sign a written informed consent document.
• Reproductive status
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 24 hours prior to the start of study treatment.

You may not qualify if:

• Known or suspected CNS metastases, with the following exceptions:
• a) Subjects with controlled brain metastases will be allowed to enroll. Controlled brain metastases are defined as no radiographic progression for at least 4 weeks following 18 radiation and/or surgical treatment at the time of randomization. b) Subjects must be off steroids for at least 2 weeks prior to initiation of investigational therapy c) Subjects with signs or symptoms of brain metastases are not eligible unless brain metastases are ruled out by computed tomography or magnetic resonance imaging.
• Medical History and Concurrent Diseases
• Patients who are receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab and BMS-986253
• Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following:
• i. Myocardial infarction (MI) or stroke/transient ischemic attack (TIA) within the 6 months prior to consent ii. Uncontrolled angina within the 3 months prior to consent iii. Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, torsades de pointes, or poorly controlled atrial fibrillation) within a month prior to consent iv. QTc prolongation \> 480 msec v. History of other clinically significant cardiovascular disease (i.e., cardiomyopathy, congestive heart failure with New York Heart Association \[NYHA\] functional classification III-IV, pericarditis, significant pericardial effusion, significant coronary stent occlusion, poorly controlled deep venous thrombosis, etc) vi. Cardiovascular disease-related requirement for daily supplemental oxygen vii. History of two or more coronary revascularization procedures within the 3 months prior to consent viii. Subjects with history of myocarditis, regardless of etiology
• A confirmed history of encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent
• Subjects with history of life-threatening toxicity related to prior immune therapy (eg. anti-CTLA-4 or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) except those that are unlikely to re-occur with standard countermeasures (eg, hormone replacement after endocrinopathy).
• Subject has been administered prior chemotherapy or immunotherapy at any time, and any with radiation therapy within 4 weeks prior to time of consent or who has not recovered (ie, ≤ Grade 1 or at baseline) from adverse events due to previously administered agent.
• Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Subjects with endocrinopathy which is adequately controlled with hormone replacement therapy are an exception to this criterion and may qualify for the study.
• If subject underwent major surgery, subject must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Subject has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.

Sponsors & Collaborators

• Yana Najjar: lead
• Bristol-Myers Squibb: collaborator

Study Sites (2)

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

RECRUITING

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

MeSH Terms

Conditions

Melanoma; Neoplasms; Neoplasms by Histologic Type; Neoplasms by Site

Interventions

Nivolumab; spartalizumab; HuMax-IL8; Radiosurgery

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Yana Najjar, MD, FACP

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Danielle L Bednarz, BSN

CONTACT

412-623-1191; bednarzdl@upmc.edu

Amy Rose, BSN

CONTACT

412-647-8587; kennaj@upmc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 25, 2020
• First Posted: October 1, 2020
• Study Start: November 29, 2021
• Primary Completion: May 17, 2024
• Study Completion (Estimated): May 31, 2027
• Last Updated: August 1, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)