Immunotherapy + Chemotherapy for Pancreatic Cancer

Overseen by Zev A. Wainberg

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Jonsson Comprehensive Cancer Center

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Recurrent cancer, Peripheral neuropathy, HIV, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a combination of immune-boosting drugs and chemotherapy for patients with difficult-to-treat pancreatic cancer. The treatment aims to enhance the immune system and kill cancer cells more effectively than chemotherapy alone.

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

The trial requires that you stop taking immunosuppressive medications, like high-dose corticosteroids, at least 2 weeks before starting the study treatment. However, low doses of corticosteroids or short-term use may be allowed. For other medications, the protocol does not specify, so it's best to discuss with the trial team.

What data supports the effectiveness of the drug combination used in the Immunotherapy + Chemotherapy for Pancreatic Cancer trial?

Research shows that the FOLFIRINOX regimen, which includes fluorouracil, leucovorin, irinotecan, and oxaliplatin, improves survival in patients with advanced pancreatic cancer compared to single-agent treatments. This suggests that the combination of these drugs can be effective in treating pancreatic cancer. ^{1 2 3 4 5}

What makes the Immunotherapy + Chemotherapy treatment for pancreatic cancer unique?

This treatment combines immunotherapy (which helps the immune system fight cancer) with chemotherapy drugs like Fluorouracil, Irinotecan, Leucovorin Calcium, and Oxaliplatin, which are part of the FOLFIRINOX regimen, and adds new agents like Quemliclustat and Zimberelimab. This combination aims to enhance the body's immune response against pancreatic cancer, which is different from standard treatments that primarily focus on directly killing cancer cells. ^{2 3 4 6 7}

Research Team

Zev A. Wainberg

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Eligibility Criteria

Adults with borderline resectable or locally advanced pancreatic adenocarcinoma, who have not been treated before and are in good physical condition (ECOG 0-1). They must have adequate blood counts, organ function, and agree to use effective contraception. Excluded are those with severe neuropathy, active infections requiring IV treatment within 14 days of the trial start, uncontrolled medical conditions, recent major surgery or trauma within 28 days prior to first dose of study drug, known poorly-controlled HIV/HBV/HCV infection or other serious comorbidities.

Inclusion Criteria

- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L

You have been diagnosed with pancreatic cancer for the first time and it has been confirmed by a medical test.

The tumor in your body is connected to an important blood vessel in a way that covers at least half of the vessel's surface.

Exclusion Criteria

-- Active viral, bacterial, or fungal infections requiring parenteral treatment within 14 days of the initiation of the IP

You have type 1 diabetes, hypothyroidism that only needs hormone replacement, or certain skin disorders.

You have a medical condition or side effects from a previous experimental drug that could make it difficult to understand the new drug's effects or side effects.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive zimberelimab, quemliclustat, and chemotherapy (mFOLFIRINOX) intravenously. Blood samples and CT scans are collected throughout the trial.

Up to 2 years

Regular visits for IV administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including progression-free survival and overall survival assessments.

90 days after the last dose

Treatment Details

Interventions

• Fluorouracil (Chemotherapy)
• Irinotecan (Chemotherapy)
• Leucovorin Calcium (Chemotherapy)
• Oxaliplatin (Chemotherapy)
• Quemliclustat (Monoclonal Antibodies)
• Zimberelimab (Monoclonal Antibodies)

Trial Overview The trial is testing a combination therapy for pancreatic cancer that includes zimberelimab (an immunotherapy drug), quemliclustat (a blocker for adenosine which may improve immune response against cancer), and chemotherapy drugs like oxaliplatin and irinotecan. The goal is to see if this combo works better than chemotherapy alone at killing cancer cells.

Participant Groups

Group I: Treatment (zimberelimab, quemliclustat, chemotherapy) Experimental Treatment 10 Interventions

Patients receive zimberelimab IV, quemliclustat IV, oxaliplatin IV, leucovorin calcium IV, and inrinotecan IV on study. Patients undergo collection of blood samples and CT throughout the trial. Patients with borderline-resectable pancreatic cancer undergo collection of tissue samples. Patients with locally advanced pancreatic cancer undergo core biopsy.

Fluorouracil is already approved in Canada for the following indications:

Approved in Canada as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

Dr. Aparna Bhaduri

Jonsson Comprehensive Cancer Center

Chief Medical Officer since 2024

MD

Dr. Michael A. Teitell

Jonsson Comprehensive Cancer Center

Chief Executive Officer since 2024

MD, PhD

Arcus Biosciences, Inc.

Industry Sponsor

Trials

44

Recruited

7,500+

Findings from Research

In a study of 485 patients with localized pancreatic cancer, those treated with FOLFIRINOX showed higher rates of partial response according to RECIST criteria compared to those treated with gemcitabine plus nab-paclitaxel (GA), indicating better initial tumor response.

Despite the higher response rates and more frequent surgeries (pancreatectomy) in the FOLFIRINOX group, overall survival rates were similar between the two treatment regimens, suggesting that while FOLFIRINOX may be more effective in shrinking tumors, it does not necessarily lead to longer survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response and Survival Associated With First-line FOLFIRINOX vs Gemcitabine and nab-Paclitaxel Chemotherapy for Localized Pancreatic Ductal Adenocarcinoma. Perri, G., Prakash, L., Qiao, W., et al.[2022]

In a study of 1102 patients with metastatic pancreatic cancer, FOLFIRINOX treatment resulted in a median overall survival of 9.27 months, significantly longer than the 6.87 months observed with gemcitabine plus nab-paclitaxel (P < 0.001).

Patients receiving FOLFIRINOX also experienced 17.3% fewer posttreatment hospitalizations and 20% lower posttreatment costs compared to those treated with gemcitabine plus nab-paclitaxel, indicating better safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of FOLFIRINOX vs Gemcitabine Plus Nab-Paclitaxel as First-Line Chemotherapy for Metastatic Pancreatic Ductal Adenocarcinoma. Klein-Brill, A., Amar-Farkash, S., Lawrence, G., et al.[2023]

A study of 5465 patients with advanced pancreatic cancer in Ontario showed that the introduction of new chemotherapy regimens, GEMNAB and FOLFIRINOX, significantly improved overall survival rates over time, with median survival increasing from 5.6 months to 7.6 months between 2008 and 2018.

FOLFIRINOX was found to provide better overall survival compared to GEMNAB, particularly in younger and healthier patients, while GEMNAB still showed improved survival compared to the older standard treatment, gemcitabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Association of Drug-Funding Reimbursement With Survival Outcomes and Use of New Systemic Therapies Among Patients With Advanced Pancreatic Cancer. Raphael, MJ., Raskin, W., Habbous, S., et al.[2023]

The introduction of FOLFIRINOX and gemcitabine plus nab-paclitaxel therapy significantly improved treatment outcomes for metastatic pancreatic cancer, with response rates increasing from 7.8% to 28.4% after these therapies were introduced.

Patients treated with the newer therapies experienced longer median progression-free survival (3.1 months to 5.4 months) and median overall survival (6.7 months to 10.2 months), indicating a substantial benefit in daily clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement of Treatment Outcomes for Metastatic Pancreatic Cancer: A Real-world Data Analysis. Sasaki, T., Kanata, R., Yamada, I., et al.[2022]

Systemic treatments for metastatic pancreatic adenocarcinoma, such as gemcitabine, provide modest survival benefits, with gemcitabine showing improved outcomes over 5-fluorouracil (5-FU) and best supportive care.

Combination therapies involving gemcitabine with other agents like platinum drugs or taxanes have shown improved response rates and progression-free survival, but overall survival benefits remain limited, highlighting the need for ongoing clinical trials to explore new treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic therapy for metastatic pancreatic adenocarcinoma. Lawrence, B., Findlay, M.[2023]

Gemcitabine, when combined with immune modulatory agents like oxaliplatin and pomalidomide, can enhance the immunogenicity of pancreatic tumor cells by increasing markers of immune recognition, although it may also inhibit T-cell activation.

Pomalidomide showed immune-modulating effects on dendritic cells and T-cells, suggesting that it can positively influence immune responses even when used alongside gemcitabine, highlighting the potential for combination therapies in improving treatment outcomes for pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Gemcitabine based chemotherapy on the immunogenicity of pancreatic tumour cells and T-cells. Smith, PL., Yogaratnam, Y., Samad, M., et al.[2023]

Recent studies indicate that gemcitabine, either alone or in combination with 5-fluorouracil and radiation, plays a significant role in the treatment of resected and locally advanced pancreatic cancer, although survival rates remain low.

Combination therapies involving gemcitabine with other agents like oxaliplatin or capecitabine have shown improved response rates in clinical trials, but they have not significantly enhanced overall survival according to phase III trial results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancreatic cancer: are we moving forward yet? Highlights from the Gastrointestinal Cancers Symposium. Orlando, FL, USA. January 20th, 2007. Saif, MW.[2018]

References

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

Response and Survival Associated With First-line FOLFIRINOX vs Gemcitabine and nab-Paclitaxel Chemotherapy for Localized Pancreatic Ductal Adenocarcinoma. [2022]

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

Comparison of FOLFIRINOX vs Gemcitabine Plus Nab-Paclitaxel as First-Line Chemotherapy for Metastatic Pancreatic Ductal Adenocarcinoma. [2023]

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

The Association of Drug-Funding Reimbursement With Survival Outcomes and Use of New Systemic Therapies Among Patients With Advanced Pancreatic Cancer. [2023]

4. Greece pubmed.ncbi.nlm.nih.gov

Improvement of Treatment Outcomes for Metastatic Pancreatic Cancer: A Real-world Data Analysis. [2022]

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

Systemic therapy for metastatic pancreatic adenocarcinoma. [2023]

6. Italy pubmed.ncbi.nlm.nih.gov

Effect of Gemcitabine based chemotherapy on the immunogenicity of pancreatic tumour cells and T-cells. [2023]

7. Italy pubmed.ncbi.nlm.nih.gov

Pancreatic cancer: are we moving forward yet? Highlights from the Gastrointestinal Cancers Symposium. Orlando, FL, USA. January 20th, 2007. [2018]