Quemliclustat + Chemotherapy for Pancreatic Cancer

(PRISM-1 Trial)

Recruiting at 53 trial locations

Overseen By Arcus Biosciences

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Arcus Biosciences, Inc.

Must not be taking: CD73 inhibitors

Disqualifiers: Brain metastases, Leptomeningeal metastases, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The purpose of this study is to compare overall survival of quemliclustat, nab-paclitaxel and gemcitabine versus placebo, nab-paclitaxel and gemcitabine in all randomized patients.

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.

What data supports the effectiveness of the drug Quemliclustat + Chemotherapy for Pancreatic Cancer?

Research shows that combining different chemotherapy drugs, like gemcitabine with others, can improve survival in pancreatic cancer patients. This suggests that combining Quemliclustat with chemotherapy might also be effective. ^{1 2 3 4 5}

What makes Quemliclustat + Chemotherapy unique for treating pancreatic cancer?

Quemliclustat is a novel treatment that targets specific molecular pathways in pancreatic cancer cells, which is different from traditional chemotherapy drugs like gemcitabine. This approach aims to improve outcomes by combining conventional chemotherapy with targeted therapy, potentially offering a new strategy for treating this challenging condition. ^{6 7 8 9 10}

Research Team

Medical Director

Principal Investigator

Arcus Biosciences

Eligibility Criteria

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

I am fully active or can carry out light work.

I have not been treated for pancreatic cancer after it spread.

Exclusion Criteria

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

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

I have been treated for advanced pancreatic cancer that couldn't be removed by surgery.

Trial Timeline

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

Treatment Details

Interventions

• Quemliclustat (Other)

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.

Participant Groups

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

Findings from Research

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]

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 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]

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]

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 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]

References

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

Open-label, Phase I Study of Nivolumab Combined with nab-Paclitaxel Plus Gemcitabine in Advanced Pancreatic Cancer. [2022]

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

Pancreatic Cancer Survival Increases with Chemo Combo. [2022]

3. England 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. [2022]

4. Pakistan 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. [2023]

5. 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]

6. Germany pubmed.ncbi.nlm.nih.gov

Phase I/II trial of intraperitoneal 5-Fluorouracil with and without intravenous vasopressin in non-resectable pancreas cancer. [2013]

7. Germany 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. [2018]

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

A review of systemic therapy for advanced pancreatic cancer. [2007]

9. Switzerland pubmed.ncbi.nlm.nih.gov

[Chemotherapy of pancreatic carcinoma]. [2022]

10. England 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. [2022]