Quemliclustat + Chemotherapy for Pancreatic Cancer

(PRISM-1 Trial)

Not currently recruiting at 157 trial locations

Overseen By Arcus Biosciences

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Arcus Biosciences, Inc.

Must not be taking: CD73 inhibitors

Disqualifiers: Brain metastases, Leptomeningeal metastases, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates a new treatment, quemliclustat (also known as AB680), combined with the chemotherapy drugs nab-paclitaxel and gemcitabine, to determine if it extends survival for people with metastatic pancreatic cancer compared to standard treatment with a placebo. The trial includes two groups: one receiving the experimental treatment and the other receiving standard treatment with a placebo. Suitable candidates for this trial have metastatic pancreatic cancer that has not been treated at this stage before. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that quemliclustat, the treatment being tested, is generally safe for people. In earlier studies, researchers combined quemliclustat with common chemotherapy drugs like nab-paclitaxel and gemcitabine. These studies found that patients tolerated the combination well, with no major increase in side effects compared to chemotherapy alone.

Early results also indicated that quemliclustat has a manageable safety profile, meaning any side effects were not severe and could be managed. Most people tolerated the treatment well, experiencing no serious issues. This makes it a promising option for further study in clinical trials. ^{1 2 3 4 5}

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

Unlike the standard treatments for pancreatic cancer, which typically involve chemotherapy drugs like nab-paclitaxel and gemcitabine, Quemliclustat offers a novel approach. Quemliclustat is unique because it targets a specific enzyme involved in cancer cell metabolism, potentially disrupting the growth and spread of cancer cells more effectively. Researchers are excited about this treatment because it introduces a new mechanism of action that could enhance the effectiveness of existing chemotherapy regimens. This combined approach may improve outcomes for patients who have limited options with current therapies.

What evidence suggests that quemliclustat might be an effective treatment for pancreatic cancer?

Research has shown that quemliclustat might be a promising treatment for pancreatic cancer. In this trial, participants in the experimental arm will receive quemliclustat combined with nab-paclitaxel and gemcitabine. An earlier study found that patients receiving treatments including quemliclustat lived for an average of 15.7 months, surpassing some other standard treatments. Quemliclustat also proved safe, causing few additional side effects when used with other drugs. These findings suggest that quemliclustat, when combined with chemotherapy, could improve survival for people with pancreatic cancer. ^{2 3 5 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Arcus Biosciences

Are You a Good Fit for This Trial?

This trial is for individuals with metastatic pancreatic ductal adenocarcinoma (PDAC) who haven't been treated in the metastatic setting. Participants may have had previous therapies if completed over a year before joining, or palliative radiotherapy if finished at least two weeks prior and recovered to mild symptoms.

Inclusion Criteria

I am fully active or can carry out light work.

I finished palliative radiotherapy at least 2 weeks ago and any side effects are mild.

I had a biliary stent/tube placed and any related side effects are mild.

Exclusion Criteria

Underlying medical or psychiatric conditions that, in the investigator or sponsor's opinion, will make the administration of study-specified therapy hazardous

I have had cancer spread to my brain or its coverings.

I have previously been treated with a CD73 inhibitor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either quemliclustat, nab-paclitaxel, and gemcitabine or placebo, nab-paclitaxel, and gemcitabine by IV infusion

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Quemliclustat

Trial Overview The study aims to compare the effectiveness of Quemliclustat combined with chemotherapy drugs nab-paclitaxel and gemcitabine against a placebo plus the same chemotherapy regimen, focusing on how long patients live after treatment.

How Is the Trial Designed?

Group I: Arm A (Experimental Arm) Experimental Treatment 3 Interventions

Quemliclustat, nab-paclitaxel and gemcitabine will be administered by IV infusion

Group II: Arm B (Comparator Arm) Placebo Group 3 Interventions

Placebo, nab-paclitaxel and gemcitabine will be administered by IV infusion

Who Is Running the Clinical Trial?

Arcus Biosciences, Inc.

Lead Sponsor

Trials

44

Recruited

7,500+

Taiho Pharmaceutical Co., Ltd.

Industry Sponsor

Trials

67

Recruited

18,600+

Masayuki Kobayashi

Taiho Pharmaceutical Co., Ltd.

Chief Executive Officer since 2012

Background in political and law studies

Harold Keer

Taiho Pharmaceutical Co., Ltd.

Chief Medical Officer since 2024

MD

Published Research Related to This Trial

The ESPAC-4 trial demonstrated that combining gemcitabine with capecitabine significantly improves 5-year survival rates for patients undergoing surgery for pancreatic cancer compared to gemcitabine alone.

This finding is expected to change the standard treatment approach for pancreatic cancer patients who are eligible for surgery, highlighting the importance of combination therapy in improving outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancreatic Cancer Survival Increases with Chemo Combo. [2022]

In a study of 87 patients with advanced pancreatic cancer, the FOLFIRINOX chemotherapy regimen showed the highest objective response rate (15%) and disease control rate (26%), outperforming gemcitabine and capecitabine regimens.

Patients with locally advanced pancreatic cancer had a median progression-free survival of 39 weeks, significantly longer than the 25 weeks for those with metastatic pancreatic cancer, suggesting that FOLFIRINOX may be a preferred first-line treatment in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Chemotherapy for Locally Advanced and Metastatic Pancreatic Cancer: A Real-life Experience and Outcome from a Tertiary Care Centre. Yasmeen, S., Arshad, F., Shaukat, S., et al.[2023]

In a phase I trial involving 50 patients with advanced pancreatic cancer, the combination of nivolumab, nab-paclitaxel, and gemcitabine showed a manageable safety profile, with 48 patients experiencing grade 3/4 treatment-emergent adverse events, but only one dose-limiting toxicity reported.

The treatment resulted in a median overall survival of 9.9 months and an overall response rate of 18%, indicating limited efficacy, which led to the conclusion that further investigation of this combination is not supported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label, Phase I Study of Nivolumab Combined with nab-Paclitaxel Plus Gemcitabine in Advanced Pancreatic Cancer. Wainberg, ZA., Hochster, HS., Kim, EJ., et al.[2022]

In a study of 54 patients with inoperable pancreatic cancer, the combination of docetaxel and gemcitabine showed efficacy, with 13% of patients achieving a partial response and 33% having stable disease, leading to a median overall survival of 26 weeks.

The treatment was relatively well-tolerated, with improvements in performance status and pain in a significant number of patients, although 31% experienced severe neutropenia, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of pancreatic cancer with a combination of docetaxel, gemcitabine and granulocyte colony-stimulating factor: a phase II study of the Greek Cooperative Group for Pancreatic Cancer. Stathopoulos, GP., Mavroudis, D., Tsavaris, N., 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]

Intraperitoneal 5-Fluorouracil (5-FU) treatment for patients with non-resectable pancreatic cancer was found to be safe and well-tolerated, with low toxicity and a median survival time of 8.0 months based on a study of 68 patients.

The addition of intravenous vasopressin during treatment reduced the peak concentration of 5-FU in plasma on the second day, although it did not significantly affect the overall exposure (AUC) to the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II trial of intraperitoneal 5-Fluorouracil with and without intravenous vasopressin in non-resectable pancreas cancer. Oman, M., Lundqvist, S., Gustavsson, B., et al.[2013]

In a study of 31 patients with previously treated metastatic pancreatic adenocarcinoma, the combination of docetaxel and capecitabine resulted in a disease control rate of 32.3%, with partial responses in 9.7% of patients and stable disease in 22.6%.

The treatment was associated with a median overall survival of 6.3 months and manageable side effects, including grade III/IV neutropenia in 32.2% of patients, suggesting that this combination may improve quality of life as a second-line chemotherapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second-line chemotherapy with capecitabine (Xeloda) and docetaxel (Taxotere) in previously treated, unresectable adenocarcinoma of pancreas: the final results of a phase II trial. Katopodis, O., Polyzos, A., Kentepozidis, N., et al.[2018]

Gemcitabine remains the standard treatment for advanced pancreatic cancer, but combination therapies with other chemotherapeutic agents have shown improved response rates without significantly extending survival, based on recent phase III trials.

Research is ongoing into novel therapies that target specific molecular pathways in pancreatic cancer cells, suggesting that future treatments may combine traditional chemotherapy with these new targeted approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of systemic therapy for advanced pancreatic cancer. El-Rayes, BF., Philip, PA.[2007]

In a study of 190 patients with advanced pancreatic cancer, the three chemotherapy regimens (CapOx, CapGem, and mGemOx) showed similar efficacy, with median progression-free survival rates of 4.2 months, 5.7 months, and 3.9 months, respectively.

While all regimens had manageable toxicity profiles, the Gem-containing treatments (CapGem and mGemOx) were associated with higher rates of severe hematological toxicities, indicating that while effective, they may require closer monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine plus oxaliplatin (CapOx) versus capecitabine plus gemcitabine (CapGem) versus gemcitabine plus oxaliplatin (mGemOx): final results of a multicenter randomized phase II trial in advanced pancreatic cancer. Boeck, S., Hoehler, T., Seipelt, G., et al.[2022]

Chemotherapy regimens using gemcitabine or 5-FU have been shown to provide benefits for patients with advanced pancreatic carcinoma.

Adjuvant chemotherapy after complete surgical removal of the tumor may improve survival rates, as indicated by some studies, highlighting the potential for enhanced treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chemotherapy of pancreatic carcinoma]. Lutz, MP.[2022]

Citations

1. 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 ...

2. 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.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9381133/

Targeting CD73 with AB680 (Quemliclustat), a Novel and ... In humans, initial data show that AB680 is well tolerated and exhibits a pharmacokinetic profile (long half-life) suitable for intravenous administration (36, ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06608927

NCT06608927 | Study of Quemliclustat and Chemotherapy ... The purpose of this study is to compare overall survival of quemliclustat, nab-paclitaxel and gemcitabine versus placebo, nab-paclitaxel and gemcitabine in all ...

5. 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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04104672

A Study to Evaluate the Safety and Tolerability of AB680 ... This is a Phase 1, open-label, dose-escalation, and dose-expansion, with a gated randomization portion, study to evaluate the safety, tolerability, ...

7. 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 ...