Immunotherapy + SBRT for Solid Cancers

Recruiting at 1 trial location

Overseen By Julie Urban, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Jason J. Luke, MD

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 tests a new treatment combining radiation, nivolumab, and BMS-986253 for patients with advanced cancers who haven't responded to other treatments. The goal is to find safe doses and see if this combination can help the immune system fight cancer more effectively. Nivolumab, often combined with ipilimumab, has shown promising results in improving survival rates in various cancers, including melanoma.

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 the combination of immunotherapy and SBRT generally safe for humans?

Immunotherapy drugs like nivolumab, which are used in combination with other treatments, have been associated with some side effects, including inflammation of the colon (colitis), liver enzyme changes, skin rash, thyroid issues, and lung inflammation. These side effects are generally rare and can often be managed with early intervention. ^{1 2 3 4 5}

What makes the treatment with BMS-986253 and Nivolumab unique for solid cancers?

This treatment combines immunotherapy with stereotactic body radiotherapy (SBRT), using Nivolumab, a drug that blocks a protein called PD-1 to help the immune system attack cancer cells. This combination is unique because it aims to enhance the body's immune response against cancer by using both a targeted drug and precise radiation therapy. ^{6 7 8 9 10}

What data supports the effectiveness of the treatment combining immunotherapy and SBRT for solid cancers?

Research suggests that combining stereotactic body radiotherapy (SBRT) with immunotherapy, like nivolumab, can enhance the immune response and improve disease control in patients with certain types of cancer, such as non-small cell lung cancer (NSCLC). This combination has shown potential in improving outcomes for patients with limited metastases, known as oligometastases. ^{7 9 11 12 13}

Who Is on the Research Team?

Jason Luke, MD

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?

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

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]

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]

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]

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]

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]

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 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]

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, 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]

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]

Citations

1. United States 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. [2022]

2. United States 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. [2022]

3. Australia pubmed.ncbi.nlm.nih.gov

Prior or concurrent radiotherapy and nivolumab immunotherapy in non-small cell lung cancer. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Oligometastasis and local ablation in the era of systemic targeted and immunotherapy. [2021]

5. Ireland 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. [2023]

6. England 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. [2021]

7. United States 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. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Imaging and clinical manifestations of immune checkpoint inhibitor-related colitis in cancer patients treated with monotherapy or combination therapy. [2021]

10. England 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. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. [2023]

12. England 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. [2023]

13. England pubmed.ncbi.nlm.nih.gov

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