What side effects are associated with this type of intervention?

Common treatments for pancreatic cancer, such as the combination of nab-paclitaxel and gemcitabine, are associated with several side effects. These include neutropenia, fatigue, neuropathy, and gastrointestinal issues like nausea and diarrhea. In the AB680 trial, additional side effects from immunotherapy agents like Zimberelimab may include skin reactions, endocrine events, and immune-related adverse effects. Overall, patients may experience a range of hematologic and non-hematologic toxicities, which should be closely monitored by healthcare providers.

What prior FDA approvals exist?

The FDA has approved several treatments for pancreatic cancer, including combinations of chemotherapy agents such as gemcitabine and nab-paclitaxel. These combinations are similar to those being studied in the AB680 trial, which evaluates AB680 (a CD73 inhibitor) in combination with Zimberelimab (AB122), nab-paclitaxel, and gemcitabine. While specific FDA approvals for CD73 inhibitors in pancreatic cancer are not mentioned, the use of gemcitabine and nab-paclitaxel is well-established in the treatment landscape for advanced pancreatic cancer.

What other types of research exist?

Promising novel alternatives to AB680 for pancreatic cancer patients include: 1) The combination of an agonist CD40 monoclonal antibody (CP-870,893) with gemcitabine, which has shown to be well tolerated and induces cytokines, B cell activation, and clinical responses. 2) The dual mTORC1/mTORC2 inhibitor KU-0063794, which has demonstrated efficacy in preventing sphere formation in CD133+ pancreatic cancer cells, indicating potential against cancer stem cell-like properties.

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Other

Combination Therapy for Pancreatic Cancer (ARC-8 Trial)

Phase 1

Recruiting

Research Sponsored by Arcus Biosciences, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The measurable lesion must be outside of a radiation field if the participant received prior radiation

Naïve to any prior treatment, including chemotherapy, biological therapy, or targeted therapy for metastatic disease

Timeline

Screening 3 weeks

Treatment Varies

Follow Up first dose date to date of death, up to 1 year

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new drug, AB680, combined with three other drugs in patients with advanced pancreatic cancer. The goal is to enhance the immune system's response and use chemotherapy to fight the cancer.

Who is the study for?

This trial is for adults with advanced pancreatic cancer who haven't had treatment for metastatic disease. They must be able to consent, not pregnant, and have adequate organ function. Prior therapy is okay if it was over 6 months ago. Participants can't join if they've recently used certain steroids, had live vaccines, or have active infections or autoimmune diseases.

What is being tested?

The study tests AB680 combined with Zimberelimab, Nab-paclitaxel, and Gemcitabine in patients with advanced pancreatic cancer. It's a Phase 1 trial focusing on safety and how the body processes the drugs (pharmacokinetics), as well as their effects on the body (pharmacodynamics) and early signs of effectiveness.

What are the potential side effects?

Potential side effects may include reactions at the infusion site, changes in blood counts leading to increased infection risk or bleeding problems, fatigue, allergic responses, liver inflammation, nausea and vomiting due to chemotherapy agents like Nab-paclitaxel and Gemcitabine.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have at least one tumor that can be measured and it's not in an area treated with radiation.

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I have not received any treatment for my metastatic disease.

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I am 18 years old or older.

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I am fully active or restricted in physically strenuous activity but can do light work.

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My cancer is a type of pancreatic cancer confirmed by lab tests.

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I stopped taking high doses of steroids or similar medicines more than 2 weeks ago.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ first dose date to date of death, up to 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~first dose date to date of death, up to 1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and first dose date to date of death, up to 1 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Therapeutic procedure

Secondary study objectives

AB680 area under the plasma concentration versus time curve (AUC)

AB680 peak plasma concentration (Cmax)

AB680 time of peak concentration (Tmax)

+9 more

Other study objectives

Cytokine

AB680 gene expression

AB680 immunophenotyping

+1 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

6Treatment groups

Experimental Treatment

Group I: Dose Expansion(AB680+Zimberelimab+nab-paclitaxel(NP) & gemcitabine (Gem):Cohort A1 (front-line/1L)Experimental Treatment4 Interventions

Participants with advance pancreatic cancer, naïve to any prior treatment will receive AB680 (at the RP2D identified during dose escalation) combined with Zimberelimab and the standard nab-paclitaxel (NP) and gemcitabine (Gem) (NP/Gem) chemotherapy regimen

Group II: Dose Expansion (AB680 + Zimberelimab + NP/Gem): Cohort C (front-line/1L)Experimental Treatment4 Interventions

Participants with advance pancreatic cancer naïve to any prior treatment will receive AB680 combined with Zimberelimab and NP-Gem chemotherapy regimen.

Group III: Dose Expansion (AB680 + Zimberelimab + NP/Gem): Cohort B (second-line/2L)Experimental Treatment4 Interventions

Participants with advance pancreatic cancer who have received 1 prior line of treatment will receive AB680 (at the RP2D identified during dose escalation) combined with Zimberelimab and NP-Gem chemotherapy regimen.

Group IV: Dose Expansion (AB680 + NP/Gem): Cohort D (front-line/1L)Experimental Treatment3 Interventions

Participants with advance pancreatic cancer naïve to any prior treatment will receive AB680 combined with NP-Gem chemotherapy regimen.

Group V: Dose Expansion (AB680 + NP/Gem): Cohort A2 (front-line/1L)Experimental Treatment3 Interventions

Participants with advance pancreatic cancer who are naïve to any prior treatment will receive AB680 (at the RP2D identified during dose escalation) and the standard NP/Gem chemotherapy regimen.

Group VI: Dose EscalationExperimental Treatment4 Interventions

Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period. The dose expansion dose level will be determined in this part with escalating doses of AB680 in combination with Zimberelimab at the recommended phase 2 dose (RP2D) and the standard nab-paclitaxel and gemcitabine chemotherapy regimen in participants with advanced pancreatic cancer.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

AB680

2018

Completed Phase 1

~100

Zimberelimab

2020

Completed Phase 2

~230

Nab-paclitaxel

2014

Completed Phase 3

~1950

Gemcitabine

2017

Completed Phase 3

~1920

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for pancreatic cancer include chemotherapy agents like gemcitabine, which inhibits DNA synthesis, and nab-paclitaxel, which stabilizes microtubules to prevent cell division. Immune checkpoint inhibitors such as pembrolizumab target PD-1/PD-L1 pathways to enhance the immune system's ability to attack cancer cells. AB680, a CD73 inhibitor, works by blocking the CD73 enzyme, which is involved in the production of adenosine, a molecule that suppresses immune responses. By inhibiting CD73, AB680 aims to reduce adenosine levels, thereby enhancing anti-tumor immunity. These mechanisms are crucial for pancreatic cancer patients as they target the cancer cells directly and modulate the immune system to improve treatment efficacy and potentially overcome the tumor's resistance to therapy.

Promising new therapies in advanced pancreatic adenocarcinomas.