SX-682 + Nivolumab for Pancreatic Cancer

Overseen By Chris LeFeber

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Rochester

Must not be taking: Immunosuppressants, Corticosteroids, Investigational drugs, others

Disqualifiers: Active brain metastases, Heart disease, Autoimmune disease, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 2

Duration: 16 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals with metastatic pancreatic ductal adenocarcinoma, an advanced form of pancreatic cancer. The goal is to determine the highest safe dose of SX-682, an experimental treatment, when combined with nivolumab, a drug that aids the immune system in attacking cancer cells. Participants should have completed at least 16 weeks of initial chemotherapy without cancer progression. This trial may suit those who have finished their first round of treatment and still have measurable cancer. 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 new therapy.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot use other investigational drugs, medications at immunosuppressive doses, or certain botanical preparations within 28 days before starting the study drug. It's best to discuss your current medications with the study team.

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

The trial information does not specify if you need to stop taking your current medications. However, you cannot use other investigational drugs or medications at immunosuppressive doses within 28 days before starting the study drugs.

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

Research has shown that SX-682, when combined with nivolumab, was safe in earlier studies. The body absorbs SX-682 well as a pill, maintaining steady blood levels, and most patients have tolerated it well.

Nivolumab, an immune therapy administered through an IV, has been used in many treatments. Some individuals have experienced side effects, such as inflammation of the pancreas or colon, due to its immune-boosting effects.

Both treatments have undergone safety studies, but this trial remains in its early stages. The primary goal is to determine the safest dose for using both together. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pancreatic cancer?

Researchers are excited about SX-682 combined with Nivolumab for pancreatic cancer because it introduces a novel approach to treatment. Unlike traditional chemotherapy, which targets rapidly dividing cells, SX-682 works by inhibiting the CXCR1/2 receptors, potentially reducing the tumor's ability to resist immune attack. Nivolumab, on the other hand, is an immunotherapy that helps activate the immune system to recognize and fight cancer cells more effectively. This combination aims to not only directly attack the cancer but also enhance the body's natural defenses, offering a promising new avenue for tackling this challenging disease.

What evidence suggests that SX-682 and Nivolumab could be effective for pancreatic cancer?

In this trial, participants will receive a combination of SX-682 and Nivolumab. Research has shown that Nivolumab, a drug that helps the immune system fight cancer, has extended the lives of people with pancreatic cancer and is usually well-tolerated. SX-682 is a pill targeting proteins involved in cancer growth and spread. Although specific information about using SX-682 with Nivolumab for pancreatic cancer is limited, earlier studies with SX-682 and other treatments have shown promising results. These studies reported that the cancer either shrank or disappeared and that the treatment effectively controlled the disease. Overall, this combination is being studied for its potential to better manage the progression of pancreatic cancer. ^{1 2 3 5 6}

Who Is on the Research Team?

Daniel Mulkerin, MD

Principal Investigator

University of Rochester Wilmot Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with metastatic pancreatic ductal adenocarcinoma who've completed at least 16 weeks of first-line chemo without the cancer getting worse. They must be able to perform daily activities (ECOG status 0 or 1) and not have brain metastases, active pneumonitis, recent major surgery, other cancers in the last three years, or use immunosuppressants. Participants need functioning organs and can't be pregnant or breastfeeding.

Inclusion Criteria

Patient must consent for baseline and on treatment biopsies

Subjects must have the nature of the study explained to them

After signing the ICF and HIPAA Authorization, subjects will be evaluated for study eligibility during the Screening Period (no more than 28 days before study drug administration) according to the following further inclusion/exclusion criteria

Exclusion Criteria

I have heart disease that limits my daily activities.

You have had a serious allergic reaction to a specific type of medication called a monoclonal antibody in the past.

Your EKG shows that your heart's QTc interval is longer than 470 milliseconds.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive SX-682 in combination with Nivolumab as maintenance therapy

16 weeks

Nivolumab every 2 weeks via intravenous infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Long-term follow-up

Participants are monitored for progression-free survival and overall survival

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab
• SX-682

Trial Overview The study tests SX-682 combined with Nivolumab as a maintenance therapy to find the highest dose patients can tolerate. It's for those whose disease didn't progress after initial chemotherapy. The goal is to see how well they handle this combination treatment and what effects it has on their cancer.

How Is the Trial Designed?

Group I: Experimental: SX-682 and Nivolumab Experimental Treatment 2 Interventions

SX-682 Dose: 25, 50, 100, 200, 400mg BID taken as an oral pill Nivolumab Dose: 240mg, every 2 weeks via intravenous infusion

Who Is Running the Clinical Trial?

University of Rochester

Lead Sponsor

Trials

883

Recruited

555,000+

Syntrix Biosystems, Inc.

Industry Sponsor

Trials

14

Recruited

810+

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

Nivolumab and ipilimumab, two FDA-approved immunotherapeutic agents targeting PD-1 and CTLA-4, are effective in treating various cancers but can cause significant immune-related adverse effects (irAEs).

In a case study of a 66-year-old female patient, steroid-resistant colitis induced by these checkpoint inhibitors was successfully treated with infliximab, highlighting a potential management strategy for severe irAEs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Immune Checkpoint Inhibitor Induced Colitis with Infliximab. Tidwell, C., Gutnik, S.[2020]

A 43-year-old woman with advanced pancreatic cancer experienced immune-related encephalopathy as a side effect of toripalimab combined with chemotherapy, highlighting the potential for serious neurological adverse events during treatment.

The patient's symptoms, including stuttering and MRI findings of cerebral white matter changes, resolved after stopping toripalimab and administering corticosteroids, emphasizing the importance of monitoring for rare neurological side effects in patients receiving immune checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stuttering as a signal of encephalopathy associated with toripalimab in a pancreatic ductal adenocarcinoma patient: a case report. He, J., Chen, X., Cheng, K., et al.[2023]

In a meta-analysis of 2,946 cancer patients, the combination therapy of nivolumab and ipilimumab was found to significantly increase the risk of immune-related adverse events (irAEs) compared to nivolumab alone.

Patients receiving the combination therapy experienced higher rates of various irAEs, including skin reactions, gastrointestinal issues, and liver enzyme elevation, indicating a need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of immune-related adverse events associated with ipilimumab-plus-nivolumab and nivolumab therapy in cancer patients. Zhou, S., Khanal, S., Zhang, H.[2022]

In a study of 84 patients with refractory metastatic pancreatic cancer, the combination of stereotactic body radiotherapy (SBRT) with nivolumab and ipilimumab showed a clinical benefit rate of 37.2%, indicating a significant improvement compared to 17.1% for SBRT with nivolumab alone.

The treatment was associated with a manageable safety profile, with 24.4% of patients experiencing grade 3 or higher adverse events in the SBRT/nivolumab group and 30.2% in the SBRT/nivolumab/ipilimumab group, suggesting that this combination therapy may be a viable option for patients despite the unknown contribution of SBRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase II Study of Nivolumab With or Without Ipilimumab Combined With Stereotactic Body Radiotherapy for Refractory Metastatic Pancreatic Cancer (CheckPAC). Chen, IM., Johansen, JS., Theile, S., 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]

Nivolumab, an immune checkpoint inhibitor, can lead to immune-related adverse events such as ICI-pancreatic injury (ICI-PI), which may present with symptoms like cholestatic liver disease, as seen in a case of a 60-year-old man with metastatic acral melanoma.

The case highlights that ICI-PI can mimic autoimmune pancreatitis, with imaging changes appearing before symptoms, emphasizing the need for prompt recognition and treatment of these adverse effects as the use of immune checkpoint inhibitors increases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case Report: Nivolumab-Induced Autoimmune Pancreatitis. Goyal, P., Moyers, JT., Elgohary, BG., et al.[2022]

Nivolumab and pembrolizumab, both PD-1 inhibitors, show a lower risk of severe treatment-related adverse effects (AEs) compared to standard care, with a relative risk of 0.39 for grade 3/4 AEs based on a meta-analysis of 9 trials involving 5,353 patients.

While these therapies are generally well tolerated, they are associated with a significantly increased risk of thyroid dysfunction (hyperthyroidism and hypothyroidism) and skin conditions like pruritus and vitiligo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity profile of approved anti-PD-1 monoclonal antibodies in solid tumors: a systematic review and meta-analysis of randomized clinical trials. Costa, R., Carneiro, BA., Agulnik, M., et al.[2022]

The combination of GVAX vaccine with nivolumab and urelumab significantly increased the number of activated CD8+ CD137+ T cells in tumors, indicating a robust immune response, and was well-tolerated by patients.

While the median disease-free and overall survival rates were numerically improved with the combination therapy compared to other treatment arms, the results were not statistically significant, suggesting that further studies are needed to confirm these promising findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A platform trial of neoadjuvant and adjuvant antitumor vaccination alone or in combination with PD-1 antagonist and CD137 agonist antibodies in patients with resectable pancreatic adenocarcinoma. Heumann, T., Judkins, C., Li, K., et al.[2023]

Immune checkpoint inhibitors like nivolumab, used for treating advanced cancers such as renal cell carcinoma, can lead to rare but serious immune-related adverse events (irAEs), including acute pancreatitis and colitis.

In this case, the patient experienced these irAEs simultaneously but showed significant improvement after receiving corticosteroid therapy, highlighting the importance of monitoring and managing side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Simultaneous Onset of Pancreatitis and Colitis as Immune-related Adverse Events in a Patient Receiving Nivolumab Treatment for Renal Cell Carcinoma. Yazaki, T., Moriyama, I., Tobita, H., et al.[2022]

In a murine model of metastatic pancreatic ductal adenocarcinoma (PDAC), combining an anti-CD137 agonist antibody with a GVAX cancer vaccine and anti-PD-1 therapy significantly improved survival rates, indicating a promising new treatment strategy.

The combination therapy enhanced T cell activation and increased the expression of costimulatory molecules, suggesting that targeting CD137 can effectively boost the immune response against PDAC, as supported by immunohistochemistry findings in human PDAC samples.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD137 agonist-based combination immunotherapy enhances activated, effector memory T cells and prolongs survival in pancreatic adenocarcinoma. Muth, ST., Saung, MT., Blair, AB., et al.[2022]

In a phase 2 trial with 105 patients suffering from metastatic pancreatic ductal adenocarcinoma (PDAC), the combination of nivolumab (an anti-PD-1 therapy) with chemotherapy showed a significant improvement in 1-year overall survival (57.7%) compared to historical data (35%).

The combination of sotigalimab (a CD40 agonistic antibody) with chemotherapy did not meet the primary survival endpoint, indicating that nivolumab may be a more effective option in this treatment setting, while distinct immune signatures were identified that could help tailor future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotigalimab and/or nivolumab with chemotherapy in first-line metastatic pancreatic cancer: clinical and immunologic analyses from the randomized phase 2 PRINCE trial. Padrón, LJ., Maurer, DM., O'Hara, MH., et al.[2023]

Nivolumab (Opdivo) significantly improves overall survival and response rates in previously-treated patients with advanced nonsquamous non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CheckMate 057 trial.

Nivolumab has a manageable adverse event profile and is better tolerated than docetaxel, making it a valuable treatment option for patients who have progressed after chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. Keating, GM.[2018]

Nivolumab, an immune checkpoint inhibitor, significantly improves overall survival and progression-free survival in patients with advanced stage squamous cell non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CHECKMATE 017 study.

The safety and tolerability of nivolumab are favorable, and interestingly, the expression of the PD-L1 ligand does not predict treatment outcomes, suggesting that other factors may influence the effectiveness of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab in the treatment of metastatic squamous non-small cell lung cancer: a review of the evidence. Lim, JS., Soo, RA.[2018]

Nivolumab and pembrolizumab are FDA-approved monoclonal antibodies that target PD-1, helping to enhance T cell activity against cancer by blocking the PD-1/PD-L1 interaction, which allows cancer cells to escape immune detection.

Both drugs have shown efficacy across multiple cancer types, including melanoma and non-small cell lung cancer, and are considered interchangeable options for treating these conditions, which may help manage the rising costs of cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. Prasad, V., Kaestner, V.[2022]

Nivolumab (Opdivo) monotherapy led to complete regression of local recurrence and multiple lung metastases in a patient with recurrent skin melanoma and a positive BRAF mutation, demonstrating its efficacy as a treatment option.

After 5 courses of nivolumab, the patient experienced significant improvement in her condition, achieving an ECOG performance status of 0, indicating a return to an active lifestyle without pain, and normal serum LDH levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[EVALUATION OF THE EFFICASY OF THE DRUG OPDIVO (NIVOLUMAB) IN A PATIENT DIAGNOSED WITH UNRESECTABLE SKIN MELANOMA, POSITIVE BRAF MUTATION AND DISEASE DISSEMINATION (CASE REPORT)]. Samsonia, M., Kandelaki, M., Gibradze, O., et al.[2021]

Citations

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A phase I study to evaluate the safety and tolerability of SX- ... Background: Survival outcomes for advanced pancreatic ductal adenocarcinoma (PDAC) remain dismal despite improvements in systemic therapy ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04477343

NCT04477343 | A Study to Evaluate the Safety and ... The main purpose of this research study is to determine the maximum tolerable dose (MTD) of SX-682 in combination with nivolumab in patients with metastatic ...

3. withpower.com withpower.com/trial/phase-1-pancreatic-neoplasms-10-2020-39ebc

SX-682 + Nivolumab for Pancreatic Cancer In these cases, Nivolumab has shown to improve survival rates and is better tolerated compared to some other treatments. However, without specific data on ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.9508

Safety and efficacy of first-in-class CXCR1/2 inhibitor SX ... SX-682 combined with pem had a tolerable safety profile and activity reflected by objective responses and clinically meaningful disease control.

5. researchgate.net researchgate.net/publication/358267744_A_phase_I_study_to_evaluate_the_safety_and_tolerability_of_SX-682_in_combination_with_PD-1_inhibitor_as_maintenance_therapy_for_unresectable_pancreatic_adenocarcinoma

A phase I study to evaluate the safety and tolerability of SX ... We are currently conducting a Phase I study (NCT04477343) evaluating SX-682, an oral CXCR1/2 inhibitor, and Nivolumab as maintenance treatment ...

6. clin.larvol.com clin.larvol.com/trial-detail/NCT04477343

A Study to Evaluate the Safety and Tolerability of SX-682 in ... The drug was well tolerated and absorbed with excellent dose-proportional drug levels in blood...Based on these promising results, additional Phase 1/2 trials ...