Tislelizumab + SX-682 for Pancreatic Cancer

Overseen By Colleen Apostol, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Steroids, Immunosuppressants, QT prolonging drugs

Disqualifiers: Autoimmune disease, Active infection, Uncontrolled illness, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

25 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety and clinical activity of tislelizumab (an anti-PD-1 antibody) in combination with SX-682 (a CXCR1/2 inhibitor) in subjects with newly diagnosed and surgically resectable pancreatic adenocarcinoma.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot use systemic steroids, immunosuppressive therapy, or QT prolonging drugs within 14 days before starting the study drugs. Please consult with the trial coordinators for more details.

What data supports the idea that Tislelizumab + SX-682 for Pancreatic Cancer is an effective treatment?

The available research does not provide specific data on the effectiveness of Tislelizumab + SX-682 for Pancreatic Cancer. However, Tislelizumab has shown promise in treating other types of cancers, such as esophageal, gastric, and urothelial cancers, by helping the immune system fight cancer cells. It has been effective in combination with other treatments for these cancers, but there is no direct evidence from the provided information about its effectiveness for pancreatic cancer. ^{1 2 3 4 5}

What safety data is available for Tislelizumab and SX-682 in treating pancreatic cancer?

Tislelizumab has been studied in various cancers and generally has an acceptable safety profile. Common adverse effects include fatigue, anemia, and decreased neutrophil count, with more serious events like respiratory infection or hepatic injury being less common. Specific safety data for the combination of Tislelizumab and SX-682 in pancreatic cancer is not provided in the available research. However, Tislelizumab alone has been evaluated in other cancers, showing manageable safety profiles. No specific safety data for SX-682 is mentioned in the provided research. ^{2 3 4 6 7}

Is the drug Tislelizumab a promising treatment for pancreatic cancer?

Tislelizumab is a promising drug because it has shown positive effects in treating various types of cancer, including lung, liver, and gastric cancers. It works by helping the immune system fight cancer cells more effectively. It has been approved for use in several cancers in China and has received special designations in the U.S. for certain cancers, indicating its potential as an effective cancer treatment. ^{1 2 4 5 8}

Research Team

Eric Christenson, MD

Principal Investigator

SKCCC Johns Hopkins Medical Institution

Eligibility Criteria

Adults over 18 with newly diagnosed, resectable pancreatic adenocarcinoma can join this trial. They must understand and consent to the study, have good performance status (ECOG 0 or 1), adequate organ function, agree to use birth control, and be willing to undergo a tumor biopsy.

Inclusion Criteria

Ability to understand and willingness to sign a written informed consent document

I am fully active or can carry out light work.

I am using or willing to use birth control during the study.

Exclusion Criteria

I am currently on medication for an infection.

I have a history of lung conditions like interstitial lung disease or pulmonary fibrosis.

I do not have HIV or hepatitis B or C.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive tislelizumab and SX-682 to evaluate safety and clinical activity

2 weeks

1 visit (in-person)

Surgery

Participants undergo surgical resection of pancreatic adenocarcinoma

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

Treatment Details

Interventions

• SX-682
• Tislelizumab

Trial Overview The trial is testing the safety and effectiveness of Tislelizumab combined with SX-682 in patients who've had prior chemotherapy for metastatic pancreatic cancer. It aims to see how well these drugs work before surgery (neoadjuvant therapy).

Participant Groups

Group I: Arm A - Tislelizumab and SX-682 Experimental Treatment 2 Interventions

Tislelizumab is already approved in European Union, United States for the following indications:

Approved in European Union as Tizveni for:

• Non-small cell lung cancer (first and second line)
• Locally advanced or metastatic esophageal squamous cell carcinoma (second line)

Approved in United States as Tevimbra for:

• Unresectable or metastatic esophageal squamous cell carcinoma (second line)

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

BeiGene

Industry Sponsor

Trials

216

Recruited

32,500+

Syntrix Biosystems, Inc.

Industry Sponsor

Trials

14

Recruited

810+

Findings from Research

In a phase IA/IB study involving 451 patients with advanced solid tumors, tislelizumab demonstrated an acceptable safety profile, with most adverse events being mild (grade 1-2), and only 5.3% of patients discontinuing treatment due to side effects.

Tislelizumab showed promising antitumor activity, with 18% of patients in phase IA and 12% in phase IB achieving confirmed objective responses, leading to the recommendation of a dosing schedule of 200 mg every 3 weeks for future trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase IA/IB study of single-agent tislelizumab, an investigational anti-PD-1 antibody, in solid tumors. Desai, J., Deva, S., Lee, JS., et al.[2021]

Tislelizumab is a modified PD-1 antibody that effectively inhibits tumor growth in various cancers, including Hodgkin's lymphoma and lung cancer, and has received multiple approvals in China for its use.

It has a favorable safety profile with common side effects like fatigue and anemia, and it offers economic advantages over other PD-1 inhibitors, making it a promising option for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab: A Modified Anti-tumor Programmed Death Receptor 1 Antibody. Zhang, L., Geng, Z., Hao, B., et al.[2023]

Tislelizumab, an anti-PD-1 monoclonal antibody, showed a confirmed objective response rate of 24% in patients with PD-L1-positive urothelial carcinoma who had progressed after platinum therapy, indicating its efficacy in this challenging patient population.

The treatment had a manageable safety profile, with the most common adverse events being anemia (27%) and pyrexia (19%), and only a small percentage of patients experiencing severe side effects, suggesting that tislelizumab is a viable option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab in Asian patients with previously treated locally advanced or metastatic urothelial carcinoma. Ye, D., Liu, J., Zhou, A., et al.[2022]

In a phase II study involving 30 patients with advanced esophageal squamous cell carcinoma (ESCC) or gastric/gastroesophageal junction (G/GEJ) adenocarcinoma, the combination of tislelizumab and chemotherapy showed a confirmed objective response rate (ORR) of 46.7% and a disease control rate (DCR) of 80%.

The treatment was generally well-tolerated, with manageable side effects, although one patient experienced severe hepatic dysfunction; the median duration of response for ESCC was 12.8 months, indicating promising durability of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab Plus Chemotherapy as First-line Treatment for Advanced Esophageal Squamous Cell Carcinoma and Gastric/Gastroesophageal Junction Adenocarcinoma. Xu, J., Bai, Y., Xu, N., et al.[2021]

In a phase I study involving 32 patients with advanced solid tumors, the combination of ociperlimab and tislelizumab was well tolerated, with no dose-limiting toxicities reported and a recommended phase II dose established at ociperlimab 900 mg plus tislelizumab 200 mg every 3 weeks.

Preliminary results showed an overall response rate of 10% and a disease control rate of 50%, indicating some antitumor activity, which supports further investigation in phase II/III trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AdvanTIG-105: a phase I dose escalation study of the anti-TIGIT monoclonal antibody ociperlimab in combination with tislelizumab in patients with advanced solid tumors. Frentzas, S., Kao, S., Gao, R., et al.[2023]

Tislelizumab, an anti-PD-1 monoclonal antibody, shows improved progression-free survival and objective response rates in treating non-small cell lung cancer (NSCLC), especially when combined with chemotherapy, based on a review of four randomized controlled trials involving 1565 patients.

While tislelizumab is generally effective, it is associated with treatment-emergent adverse events, including significant hematologic issues and immune-mediated effects like hypothyroidism and pneumonitis, with a mortality rate from these events ranging from 3.2% to 4.2%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and efficacy of tislelizumab, alone or in combination with chemotherapy, for the treatment of non-small cell lung cancer: a systematic review of clinical trials. Daei Sorkhabi, A., ZareDini, M., Fazlollahi, A., et al.[2023]

Tocilizumab (TCZ) is associated with a higher likelihood of reporting pancreatitis compared to other drugs, with a reporting odds ratio of 1.32, based on an analysis of 3,383,910 adverse event reports from 2013 to 2019.

Out of 144 pancreatitis reports linked to TCZ, over half (51.39%) involved patients taking other medications known to potentially harm the pancreas, suggesting that while there is a noted increase in reports, it may not be solely attributable to TCZ itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of pancreatitis associated with tocilizumab use using the United States Food and Drug Administration Adverse Event Reporting System database. Kamath, A., Acharya, SD., Rao, RR., et al.[2021]

In a study of patients with localized lymph node-positive gastric cancer, the addition of Tislelizumab (an immunotherapy) to chemotherapy (XELOX regimen) resulted in a one-year disease-free survival (DFS) rate of 81.82%, compared to 71.43% for chemotherapy alone, although this difference was not statistically significant.

Both treatment groups experienced similar rates of adverse events, with most being mild (grade 1-2), indicating that Tislelizumab is well-tolerated and safe when combined with chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy and safety of adjuvant immunotherapy (Tislelizumab) plus chemotherapy vs. adjuvant chemotherapy alone in lymph node-positive patients with gastric cancer after D2 radical resection: a prospective, 2-arm, phase II study. Shi, JW., Zhou, Y., Wu, S.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase IA/IB study of single-agent tislelizumab, an investigational anti-PD-1 antibody, in solid tumors. [2021]

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

Tislelizumab: A Modified Anti-tumor Programmed Death Receptor 1 Antibody. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Tislelizumab in Asian patients with previously treated locally advanced or metastatic urothelial carcinoma. [2022]

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

Tislelizumab Plus Chemotherapy as First-line Treatment for Advanced Esophageal Squamous Cell Carcinoma and Gastric/Gastroesophageal Junction Adenocarcinoma. [2021]

5. England pubmed.ncbi.nlm.nih.gov

AdvanTIG-105: a phase I dose escalation study of the anti-TIGIT monoclonal antibody ociperlimab in combination with tislelizumab in patients with advanced solid tumors. [2023]

6. England pubmed.ncbi.nlm.nih.gov

The safety and efficacy of tislelizumab, alone or in combination with chemotherapy, for the treatment of non-small cell lung cancer: a systematic review of clinical trials. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Assessment of pancreatitis associated with tocilizumab use using the United States Food and Drug Administration Adverse Event Reporting System database. [2021]

8. Italy pubmed.ncbi.nlm.nih.gov

Clinical efficacy and safety of adjuvant immunotherapy (Tislelizumab) plus chemotherapy vs. adjuvant chemotherapy alone in lymph node-positive patients with gastric cancer after D2 radical resection: a prospective, 2-arm, phase II study. [2023]