Immunotherapy + Chemotherapy for Pancreatic Cancer

Overseen By Lisa Yonemoto

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Jonsson Comprehensive Cancer Center

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Recurrent cancer, Peripheral neuropathy, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

56 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach for treating pancreatic cancer by combining immunotherapy, which boosts the body's immune system, with chemotherapy. It uses zimberelimab, an immunotherapy drug, to help the immune system attack cancer cells, and quemliclustat, an experimental treatment, to block a chemical that might weaken this immune response. Patients with pancreatic cancer that cannot be surgically removed or has spread to nearby areas are eligible, especially if they haven't received other treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering patients the opportunity to be among the first to receive this new treatment.

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.

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

Research shows that combining zimberelimab, quemliclustat, and chemotherapy is generally safe for patients. A recent study found that the side effects of this combination were expected and manageable for doctors.

Another study on quemliclustat revealed no new safety issues, indicating no unexpected problems arose during its use. This finding reassures those considering joining the trial, suggesting the treatment is well-tolerated by the body.

Overall, evidence suggests the treatment is safe enough for further testing. Prospective participants might find this information reassuring regarding the treatment's safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of zimberelimab and quemliclustat with chemotherapy for pancreatic cancer because it introduces innovative mechanisms of action. Unlike the standard treatments such as gemcitabine and nab-paclitaxel, this approach leverages immunotherapy. Zimberelimab is an anti-PD-1 antibody that helps the immune system recognize and attack cancer cells, while quemliclustat is designed to inhibit a specific enzyme (CD73) that tumors use to evade immune detection. This dual approach not only targets the cancer directly but also enhances the body's immune response, offering a potential breakthrough for hard-to-treat pancreatic cancer.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

In this trial, participants will receive a combination of zimberelimab and quemliclustat with chemotherapy. Research has shown that this combination may help treat pancreatic cancer. One study found that patients using this combination lived for a median of 15.7 months, which is promising for this type of cancer. This treatment is considered safe and does not add significant side effects. It helps the immune system find and attack cancer cells, while chemotherapy directly kills them. Early results suggest this method might be more effective than chemotherapy alone. ^{1 3 6 7 8}

Who Is on the Research Team?

Zev A. Wainberg

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Fluorouracil
• Irinotecan
• Leucovorin Calcium
• Oxaliplatin
• Quemliclustat
• Zimberelimab

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.

How Is the Trial Designed?

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 United States, European Union, Canada for the following indications:

Approved in United States as 5-Fluorouracil for:

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

Approved in European Union as 5-Fluorouracil for:

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

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+

Arcus Biosciences, Inc.

Industry Sponsor

Trials

44

Recruited

7,500+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.665

ARC-8: Phase 1/1b randomized study of quemliclustat + ... Results from ARC-8 demonstrate the addition of Q 100 mg ± Z to G/nP was safe and tolerable, with no significant added toxicity to GnP.

2. investors.arcusbio.com investors.arcusbio.com/investors-and-media/press-releases/press-release-details/2024/Data-from-a-Phase-1b-Study-of-Quemliclustat-Based-Regimens-Showed-Promising-Overall-Survival-in-Treatment-Nave-Metastatic-Pancreatic-Cancer/default.aspx

Data from a Phase 1b Study of Quemliclustat-Based ... Median Overall Survival was 15.7 months for all patients treated with 100 mg quemliclustat-based regimens in the ARC-8 study, which exceeds ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05688215

NCT05688215 | Zimberelimab and Quemliclustat in ... This phase I/II study tests how well zimberelimab and quemliclustat work in combination with chemotherapy (mFOLFIRINOX) in treating patients pancreatic ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS4195

QUIC: Phase 2 study of gemcitabine, cisplatin, ... Q in combination with chemotherapy has demonstrated promising activity in patients with advanced pancreatic cancer without significant increase ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT321257

Phase I/Ib study to evaluate safety and tolerability of AB680 ... AB680, the first clinical-stage small-molecule CD73 inhibitor, in combination with SOC chemotherapy + Zim has a manageable safety profile consistent with that ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-10208

Zimberelimab and Quemliclustat in Combination with ... This phase I/II study tests how well zimberelimab and quemliclustat work in combination with chemotherapy (mFOLFIRINOX) in treating patients pancreatic ...

7. investors.arcusbio.com investors.arcusbio.com/investors-and-media/press-releases/press-release-details/2025/Arcus-Biosciences-Quemliclustat-Receives-Orphan-Drug-Designation-for-Pancreatic-Cancer/default.aspx

Arcus Biosciences' Quemliclustat Receives Orphan Drug ... In January 2024, Arcus presented results from the Phase 1 ARC-8 study, which showed no new safety signals and median overall survival (OS) of ...

8. gioncologynow.com gioncologynow.com/post/addition-of-quemliclustat-to-this-triplet-combination-raises-os-for-mpdac

Addition of Quemliclustat to Combination Raises OS for ... A total of 122 patients with untreated mPDAC were included in the study, with 93 patients receiving quemliclustat plus G/nP with zimberelimab, ...