Immunotherapy + SBRT for Solid Cancers

Recruiting at 1 trial location

Overseen By Danielle L Bednarz, BSN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Yana Najjar

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: CNS metastases, Autoimmune disease, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new cancer treatment that combines immunotherapy and radiation, specifically targeting solid tumors. Researchers aim to determine safe doses and evaluate the effectiveness of this combination, particularly in melanoma, a type of skin cancer. The trial includes individuals with advanced or untreatable solid tumors who have not responded to standard treatments and have 1-4 tumors that can be safely targeted with radiation. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on immunosuppressive therapy or have received chemotherapy or immunotherapy recently. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that using nivolumab and BMS-986253 with stereotactic body radiotherapy (SBRT), a type of targeted radiation, is generally safe for people with advanced solid tumors. Previous studies found that most patients tolerate this treatment well without severe side effects. However, some side effects can occur, though they are usually manageable. The ongoing study aims to determine the safest radiation dose to use with these drugs. For those considering joining a trial, this evidence suggests the treatment is relatively safe, but discussing potential risks with the trial team is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment combination because it targets cancer in a novel way. Unlike traditional therapies that often focus on one type of treatment, this approach combines immunotherapy with stereotactic body radiotherapy (SBRT) to enhance the body's immune response against tumors. Nivolumab, an anti-PD-1 drug, helps the immune system recognize and attack cancer cells, while BMS-986253, an anti-IL-8 agent, potentially disrupts the tumor's ability to evade immune detection. This dual-target strategy, combined with the precise delivery of SBRT, could lead to more effective and durable responses in treating solid cancers.

What evidence suggests that this trial's treatments could be effective for solid cancers?

Research has shown that nivolumab, a drug that helps the immune system fight cancer, is effective against several types of cancer. In this trial, participants will receive a combination of nivolumab with another drug targeting IL-8 (BMS-986253) and radiation therapy (SBRT). Studies have found that this combination is safe and may effectively treat advanced solid tumors. This approach aims to strengthen the immune system's attack on cancer and help overcome resistance to treatment. Early results suggest this combination might improve outcomes for patients with difficult-to-treat cancers like melanoma. While more research is needed, these initial findings are promising for those exploring new treatment options. ^{1 2 3 4 5}

Who Is on the Research Team?

Yana Najjar, MD, FACP

Principal Investigator

UPMC Hillman Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors like melanoma or renal cell carcinoma, who have progressed on standard therapies. They must be able to undergo radiation, have normal organ function, and not be pregnant or breastfeeding. Participants need detectable IL-8 levels in their blood and an ECOG performance status of 0 or 1.

Inclusion Criteria

You have a certain level of IL-8 in your blood at the start of the study.

I am using effective birth control if I can have children or am sexually active.

I have 1-4 tumors that can be safely treated with radiation.

Exclusion Criteria

I have specific health conditions or cancers.

You have a current, known, or suspected autoimmune disease.

I have not had chemotherapy, immunotherapy, or radiation recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Evaluation of safety and tolerability of different doses of SBRT in combination with nivolumab and BMS-986253 in participants with advanced solid tumors

8 weeks

Every 2 weeks

Treatment Part 2

Assessment of preliminary efficacy of SBRT in combination with nivolumab and BMS-986253 in participants with advanced/metastatic/unresectable melanoma

Up to 1 year

Every 2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• BMS-986253
• Nivolumab
• Stereotactic Body Radiotherapy (SBRT)

Trial Overview The study tests the safety of combining Stereotactic Body Radiotherapy (SBRT) with two immunotherapy drugs: Nivolumab (anti-PD1) and BMS-986253 (anti-IL-8). It aims to find safe radiation doses by organ site when used with these drugs and observe changes in tumor environments.

How Is the Trial Designed?

Group I: Nivolumab (Anti-PD-1) + BMS-986253 (Anti-IL-8) + SBRT Experimental Treatment 3 Interventions

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)

Who Is Running the Clinical Trial?

Yana Najjar

Lead Sponsor

Trials

7

Recruited

200+

Jason J. Luke, MD

Lead Sponsor

Trials

5

Recruited

720+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

The addition of stereotactic body radiation therapy (SBRT) to checkpoint inhibitor (CPI) immunotherapy in 35 patients with metastatic non-small cell lung cancer was found to be safe, with no severe radiation-induced toxicities (grade 3 to 5) reported.

The combination treatment resulted in a best systemic objective response rate of 53%, indicating a promising efficacy that supports the need for further randomized trials to explore this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Prospective Trial Evaluating the Safety and Systemic Response From the Concurrent Use of Radiation Therapy with Checkpoint Inhibitor Immunotherapy in Metastatic Non-Small Cell Lung Cancer. Mattes, MD., Eubank, TD., Almubarak, M., et al.[2022]

Combining stereotactic body radiation therapy (SBRT) with immunotherapy and targeted therapies shows promise in improving outcomes for patients with oligometastatic cancers, such as non-small cell lung cancer, melanoma, and kidney cancer, based on a review of studies involving at least 20 patients each.

The effectiveness of this combination therapy is highly dependent on the sequence of treatment and patient selection, particularly in cases of oligoprogressed disease, where SBRT may enhance the long-term benefits of existing targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oligometastasis and local ablation in the era of systemic targeted and immunotherapy. Mazzola, R., Jereczek-Fossa, BA., Franceschini, D., et al.[2021]

In a phase 1 trial involving 37 treatment-naive patients with stage IV NSCLC, combining concurrent stereotactic body radiotherapy (SBRT) with nivolumab and ipilimumab showed no dose-limiting toxicities, indicating a favorable safety profile for this multimodal treatment approach.

The study reported a median progression-free survival of 5.8 months and demonstrated that concurrent therapy was well tolerated, suggesting that this combination could effectively control metastasis in widely metastatic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1 Trial of Concurrent or Sequential Ipilimumab, Nivolumab, and Stereotactic Body Radiotherapy in Patients With Stage IV NSCLC Study. Bestvina, CM., Pointer, KB., Karrison, T., et al.[2022]

In a study of 85 patients with metastatic non-small cell lung cancer (NSCLC) treated with nivolumab, those who received radiotherapy (RT) prior to or during treatment had a significantly longer progression-free survival (PFS) of 2.8 months compared to 1.3 months for those who did not receive RT.

The combination of RT and nivolumab did not increase toxicity, suggesting that RT may enhance the effectiveness of anti-PD-1 therapy without adding adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prior or concurrent radiotherapy and nivolumab immunotherapy in non-small cell lung cancer. Ratnayake, G., Shanker, M., Roberts, K., et al.[2020]

The combination of ibrutinib and nivolumab demonstrated an acceptable safety profile in 141 patients with relapsed or refractory B-cell malignancies, with only one dose-limiting toxicity reported, indicating that this treatment approach is generally safe for patients.

Preliminary results showed promising efficacy, with overall response rates of 61% in high-risk chronic lymphocytic leukaemia, 33% in follicular lymphoma, and 36% in diffuse large B-cell lymphoma, suggesting that this combination therapy could be effective for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and activity of ibrutinib in combination with nivolumab in patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukaemia: a phase 1/2a study. Younes, A., Brody, J., Carpio, C., et al.[2021]

A meta-analysis of 21 trials involving 11,454 patients found that immune checkpoint inhibitors (ICIs) significantly increase the risk of various immune-related adverse events (irAEs), including colitis, liver enzyme elevation, rash, hypothyroidism, and pneumonitis compared to non-ICI treatments.

While the incidence of fatal irAEs was less than 1%, the study highlights the importance of early recognition and intervention for these adverse events to prevent complications, particularly noting that ipilimumab was linked to a higher risk of certain skin and gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive Meta-analysis of Key Immune-Related Adverse Events from CTLA-4 and PD-1/PD-L1 Inhibitors in Cancer Patients. De Velasco, G., Je, Y., Bossé, D., et al.[2023]

Immune-related colitis occurred in 3.3% of cancer patients receiving immune checkpoint inhibitors (ICIs), with common symptoms including diarrhea, nausea, and abdominal pain, and typical imaging findings of bowel wall thickening and fluid-filled colon.

The onset of colitis was similar in patients receiving monotherapy and combination therapy, but those on combination therapy were more likely to experience other immune-related adverse events (irAEs), highlighting the need for careful monitoring in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging and clinical manifestations of immune checkpoint inhibitor-related colitis in cancer patients treated with monotherapy or combination therapy. Shieh, AC., Guler, E., Pfau, D., et al.[2021]

Acute colitis negatively impacts the effectiveness of CD8+ cytotoxic T lymphocytes (CTLs) in fighting tumors, primarily due to elevated levels of IL-17A in the inflamed intestine, which hinders CTL infiltration into tumors.

Administering an anti-IL-17A neutralizing antibody can restore CTL tumor infiltration and enhance the efficacy of anti-PD-1 treatments, suggesting a potential strategy to improve immunotherapy outcomes in patients experiencing tissue damage-related IL-17A elevation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abnormal generation of IL-17A represses tumor infiltration of stem-like exhausted CD8+ T cells to demote the antitumor immunity. Zhang, R., Chen, K., Gong, C., et al.[2023]

Nivolumab, a PD-1 inhibitor, has demonstrated significant safety and efficacy in treating various advanced solid tumors, including melanoma and lung cancer, based on multiple high-level studies.

Future research should aim to identify predictive biomarkers for treatment response and explore the potential of combining nivolumab with other therapies, as well as determining the best treatment strategies and duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the pharmacodynamics, pharmacokinetics, safety and clinical efficacy of nivolumab in the treatment of solid cancers. Wong, AC., Ma, B.[2018]

Immune checkpoint antibodies targeting the PD-1/PD-L1 pathway have shown significant antitumor activity and have been approved for use as single-agent therapies in metastatic malignant melanoma and nonsmall-cell lung cancer.

Understanding the toxicities associated with PD-1/PD-L1 blockade and having effective management strategies is crucial for maximizing both the safety and efficacy of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Naidoo, J., Page, DB., Li, BT., et al.[2023]

This phase II trial aims to evaluate whether combining stereotactic body radiotherapy (SBRT) with the immune checkpoint inhibitor durvalumab can improve progression-free survival in patients with oligometastatic hormone-sensitive prostate cancer, compared to SBRT alone.

The study will involve 96 patients over 3 years, focusing on not only progression-free survival but also other important outcomes like quality of life and immune response, with the expectation that the combination treatment will be effective and have manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II trial in prostate cancer with hormone-sensitive OligometaSTatic relapse: Combining stereotactic ablative radiotherapy and durvalumab (POSTCARD GETUG P13): Study protocol. Rogé, M., Pointreau, Y., Sargos, P., et al.[2023]

Nivolumab, an anti-PD-1 antibody, was administered to a 63-year-old female patient with metastatic melanoma after renal transplantation, highlighting the potential for anti-tumor activity in high-risk patients, despite the challenges of concurrent immunosuppression.

The patient experienced acute renal allograft rejection and renal failure shortly after starting nivolumab, indicating significant risks associated with this treatment in transplant recipients, but she later showed a positive clinical response after re-challenging with nivolumab while on hemodialysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. Ong, M., Ibrahim, AM., Bourassa-Blanchette, S., et al.[2023]

The combination of the TLR7/8 agonist R848 with stereotactic body radiotherapy (SBRT) significantly enhances tumor control in pancreatic ductal adenocarcinoma (PDAC) compared to either treatment alone, as shown in murine models.

This combination therapy not only activates the immune response within the primary tumor but also improves control of liver metastases by increasing CD8+ T cell activity and altering the immunosuppressive tumor microenvironment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toll-like receptor 7/8 agonist R848 alters the immune tumor microenvironment and enhances SBRT-induced antitumor efficacy in murine models of pancreatic cancer. Ye, J., Mills, BN., Qin, SS., et al.[2023]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.TPS2681

Phase I study investigating the safety of stereotactic body ... The combination of BMS-986253 and nivolumab was safe in patients with advanced solid tumors. The present study aims to evaluate safety and ...

2. redjournal.org redjournal.org/article/S0360-3016(22)02397-5/fulltext

Stereotactic Body Radiation Therapy Plus Anti-PD1/IL8 ... The present study aims to evaluate safety and preliminary efficacy of combining BMS-986253 with nivolumab and SBRT in patients with advanced solid tumors.

3. asco.org asco.org/abstracts-presentations/ABSTRACT335081

Phase I study investigating the safety of stereotactic body ... The combination of BMS-986253 and nivolumab was safe in patients with advanced solid tumors. ... solid tumors, Melanoma (MEL) and Renal Cell Carcinoma (RCC).

4. uchicagomedicine.org uchicagomedicine.org/find-a-clinical-trial/clinical-trial/irb220367

CLINICAL TRIAL / NCT04572451 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 ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301622023975

Stereotactic Body Radiation Therapy Plus Anti-PD1/IL8 ... The present study aims to evaluate safety and preliminary efficacy of combining BMS-986253 with nivolumab and SBRT in patients with advanced solid tumors, ...