Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Symptoms and General Pathology

Carcinoma

Melanoma

Carcinoma, Renal Cell

Neoplasm Metastasis

Neoplasms by Histologic Type

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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)

Nivolumab (BMS-936558-01), 480 mg intravenous (every 4 weeks)

Treatment must be within 7 days of the last dose of radiation.

nivolumab

BMS-986253 (Anti-IL-8), 2,400 mg intravenous (every 2 weeks)

Treatment must be within 7 days of the last dose of radiation.

BMS-986253

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.

Stereotactic Body Radiotherapy (SBRT)

Jason Luke, MD, FACP

Nivolumab (and other agents affecting the anti-programmed death-1 \[anti-PD-1\] pathway) have demonstrated anti-tumor activity in multiple tumor types including non-small cell lung cancer (NSCLC), melanoma (MEL), renal cell carcinoma (RCC), and other cancers. However, there remains a large proportion of participants who do not achieve durable clinical benefit to nivolumab monotherapy. Combinations of immune-oncology (IO) agents with complimentary mechanisms as well as radiation represent a promising strategy to improve response rates to immunotherapy. In this phase I study, radiation will be used in combination with IO agents nivolumab and anti-IL-8 (BMS-986253) to assess toxicity by organ system. The study will determine the safe doses of radiation by organ site in conjunction with nivolumab and BMS-986253. The study will also provide the opportunity to evaluate changes in the tumor microenvironment induced by the treatment.

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 detectable levels of IL-8 in the serum. 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 and detectable levels of IL-8 in the serum. 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 and RCC who progressed on anti-PD-(L)1 therapy and have detectable levels of IL-8 in the serum.

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 and RCC and with serum IL-8 above the lower limit of quantitation (LLOQ) will be enrolled into efficacy phase.

This proposal is intended to incorporate SBRT as a direct therapeutic which is in contrast with other proposals evaluating response at distant sites after isolated metastasis radiation. With this intent, the results of this study will be directly applicable to potential expansion cohorts and ongoing clinical need.

Note: The Sponsor-Investigator/Study Principal Investigator of this trial is Jason J. Luke, MD at the University of Pittsburgh/UPMC . The Sponsor-Investigator of this trial at University of Chicago is Steven Chmura MD, PhD.

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

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

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.

Incidence of grade 3 or higher adverse events, by organ system, per CTCAEv5.0, determined to be definitely, probably or possibly attributed to SBRT or one or both of the immunotherapies.

The proportion of patients that experience a Complete Response (CR) or Partial Response (PR) per RECIST v1.1. Per RECIST v1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

The duration of time from first day of treatment until disease progression or date of death from any cause will be estimated with a 90% confidence interval. Progression as defined by RECIST v1.1 for target lesions: Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). For non-target lesions: Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.

Overall survival (OS) (of the cohort) which is defined as elapsed time from date of first treatment until date of death.

The total disappearance of the primary tumor and neighboring lymph node metastases without any local recurrence on long-term follow-up, per RECIST version 1.1. Complete response per RECIST v1.1 is the disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm.

The total disappearance of the primary tumor and neighboring lymph node metastases without any local recurrence on long-term follow-up, by immune-related RECIST (irRECIST). Immune Complete Response (iCR) is the complete resolution of non-nodal lesions and \< 10 mm short-axis for lymph nodes. No confirmation necessary.

Bristol-Myers Squibb

Jason J. Luke, MD

Associate Professor of Medicine

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Lymphoma

Leukemia

Hematologic Neoplasms

Hematologic Diseases

Lymphosarcoma

Vasoconstrictor Agents

Respiratory System Agents

Xylometazoline

STA-5312

The purpose of this study is to determine the safety, toxicity and patient tolerance of STA-5312 administered intravenously to patients with relapsed or refractory hematological malignancies and patients with solid tumors.

STA-5312 Administered on Alternate Weekdays Every Two Weeks to Patients With Hematologic Malignancies and Patients With Solid Tumors

Phase I Trial of STA-5312 Administered on Alternate Weekdays Every Two Weeks to Patients With Hematological Malignancies and Patients With Solid Tumors

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety of SBRT With Anti-PD1 and Anti-IL-8 for the Treatment of Multiple Metastases in Advanced Solid Tumors	NCT04572451	Melanoma Carcinoma, Rena... Unresectable So...	nivolumab BMS-986253 Stereotactic Bo...	18 Years -	University of Pittsburgh
STA-5312 Administered on Alternate Weekdays Every Two Weeks to Patients With Hematologic Malignancies and Patients With Solid Tumors	NCT00088101	Hematological M... Leukemia Lymphoma Metastatic or U...	STA-5312	18 Years -	Synta Pharmaceuticals Corp.
STA-5312 Administered on Alternate Weekdays Every Two Weeks to Patients With Hematologic Malignancies and Patients With Solid Tumors	NCT00088101	Hematological M... Leukemia Lymphoma Metastatic or U...	STA-5312	18 Years -	Synta Pharmaceuticals Corp.
STA-5312 Administered on Alternate Weekdays Every Two Weeks to Patients With Hematologic Malignancies and Patients With Solid Tumors	NCT00088101	Hematological M... Leukemia Lymphoma Metastatic or U...	STA-5312	18 Years -	Synta Pharmaceuticals Corp.

Spots Global Cancer Trial Database for unresectable solid tumors