AB598 + Chemotherapy for Advanced Cancers

(ARC-25 Trial)

Not currently recruiting at 27 trial locations

Overseen By Medical Director

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Arcus Biosciences, Inc.

Must not be taking: Live vaccines, Immunosuppressants

Disqualifiers: Autoimmune diseases, Recent surgery, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12-24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, AB598, combined with chemotherapy to determine its safety and manageability for people with advanced cancers. The study targets various solid tumors that have not responded well to standard treatments. Participants should have at least one measurable tumor, and those with gastric or certain other cancers may need to meet additional specific criteria. Individuals battling solid tumors that standard therapies cannot effectively treat might be suitable for this study. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take systemic immunosuppressive medication within 2 weeks before starting the study treatment. It's best to discuss your specific medications with the trial team.

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

Research has shown that AB598, a treatment for advanced cancers, is in the early stages of human testing. As a result, limited information exists about its safety. Early studies with AB598 focus on understanding its tolerability. Since these trials are just beginning, researchers aim to identify any side effects or negative reactions.

When combined with zimberelimab, past studies of similar treatments have found that mixing medications can sometimes cause new side effects. However, zimberelimab has been tested in other cancer trials, and early results suggested it is generally well-tolerated when used with chemotherapy.

Because these treatments are still under investigation, not all possible side effects are known. Participants in these trials are closely monitored to ensure their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about AB598 for advanced cancers because it introduces a novel mechanism of action not seen in standard treatments like carboplatin or fluorouracil. Unlike typical chemotherapies that broadly target fast-dividing cells, AB598 works by specifically modulating immune pathways to enhance the body's own ability to fight cancer cells. This targeted approach could potentially improve effectiveness while reducing the side effects commonly associated with traditional cancer therapies. Additionally, when combined with zimberelimab and FOLFOX, AB598 may offer a more comprehensive strategy by simultaneously boosting immune response and attacking cancer cells directly.

What evidence suggests that this trial's treatments could be effective for advanced cancers?

Research shows that AB598, which participants in this trial may receive, is a promising treatment for solid tumors. It blocks CD39, an enzyme that can weaken the immune system's ability to fight cancer. Early studies in animals with immune systems similar to humans have shown that AB598 can help fight tumors.

Additionally, another treatment arm in this trial involves the combination of zimberelimab and FOLFOX chemotherapy (a mix of cancer-fighting drugs), which has shown positive results in patients with advanced stomach and esophagus cancers. Studies have reported a 59% response rate and longer survival times with similar treatment combinations. Researchers are further exploring this combination for its potential to improve outcomes for cancer patients. ^{2 6 7 8 9}

Who Is on the Research Team?

Medical Director

Principal Investigator

Arcus Biosciences

Are You a Good Fit for This Trial?

This trial is for adults with certain advanced cancers, including stomach, lung, and breast cancer. Participants must have a specific performance status score and at least one measurable lesion. They should not have received prior treatment for their advanced cancer or progressed within 6 months after platinum-based chemotherapy.

Inclusion Criteria

My cancer did not worsen within 6 months after receiving platinum-based chemotherapy.

My lung cancer is not mixed with small-cell type.

Must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) guidance

Exclusion Criteria

I haven't taken immunosuppressive drugs in the last 2 weeks and don't expect to need them during the study.

I have not had major surgery or serious injury in the last 28 days.

I haven't had an autoimmune disease in the last 3 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AB598 IV infusion every 2-3 weeks, with some cohorts receiving combination therapy with zimberelimab and FOLFOX

12-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AB598
• Carboplatin
• Fluorouracil
• Leucovorin
• Oxaliplatin
• Pemetrexed
• Zimberelimab

Trial Overview The study tests the safety of AB598 alone and combined with zimberelimab plus standard chemo drugs like Pemetrexed and Oxaliplatin in patients with advanced malignancies. It aims to find out how well these treatments are tolerated by participants.

How Is the Trial Designed?

Group I: Pharmacodynamic Cohort 3 Experimental Treatment 1 Intervention

Participants will receive AB598 IV infusion once every 3 weeks

Group II: Pharmacodynamic Cohort 2 Experimental Treatment 1 Intervention

Participants will receive AB598 IV infusion once every 3 weeks

Group III: Pharmacodynamic Cohort 1 Experimental Treatment 1 Intervention

Participants will receive AB598 IV infusion once every 3 weeks

Group IV: Dose Expansion Gastric/GEJ Cancer (phase 1b) Experimental Treatment 5 Interventions

Participants will receive AB598 IV infusion every 2 weeks in combination with zimberelimab and FOLFOX (oxaliplatin, leucovorin, fluorouracil)

Group V: Dose Escalation Cohort 4 Experimental Treatment 1 Intervention

Participants will receive AB598 IV infusion once every 3 weeks

Group VI: Dose Escalation Cohort 3 Experimental Treatment 1 Intervention

Participants will receive AB598 IV infusion once every 3 weeks

Group VII: Dose Escalation Cohort 2 Experimental Treatment 1 Intervention

Participants will receive AB598 IV infusion once every 3 weeks

Group VIII: Dose Escalation Cohort 1 Experimental Treatment 1 Intervention

Participants will receive AB598 intravenous (IV) infusion once every 3 weeks

Who Is Running the Clinical Trial?

Arcus Biosciences, Inc.

Lead Sponsor

Trials

44

Recruited

7,500+

Published Research Related to This Trial

Oral fluoropyrimidines, such as capecitabine and UFT/LV, offer a more convenient and less toxic alternative to traditional intravenous 5-fluorouracil (5-FU) for treating advanced colorectal cancer (CRC).

Oxaliplatin, with a different mechanism of action than 5-FU, significantly improves response rates and time to disease progression when used in combination with 5-FU and leucovorin in first-line treatment, and is effective even in patients whose cancer has progressed after 5-FU treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel chemotherapy agents for colorectal cancer: oral fluoropyrimidines, oxaliplatin, and raltitrexed. Royce, ME., Hoff, PM., Padzur, R.[2019]

The PELF regimen (cisplatin, epirubicin, and leucovorin) demonstrated a significantly higher overall response rate (43%) compared to the FAM regimen (15%) in treating advanced gastric carcinoma, indicating its greater efficacy in inducing tumor responses.

Although the PELF combination was more effective, it also had higher toxicity compared to FAM, making it less suitable for routine clinical use despite its potential for further investigation in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluorouracil, doxorubicin, and mitomycin combination versus PELF chemotherapy in advanced gastric cancer: a prospective randomized trial of the Italian Oncology Group for Clinical Research. Cocconi, G., Bella, M., Zironi, S., et al.[2017]

In a phase II trial involving 42 chemotherapy-naïve patients with advanced pancreatic cancer, LY231514 (pemetrexed) was found to be well-tolerated, with common side effects including neutropenia in 40% of patients, but rare infectious complications.

The treatment showed minimal antitumor activity, with an objective response rate of only 5.7%, although 40% of patients experienced stable disease for at least 6 months, and the median survival was 6.5 months, suggesting potential for further investigation in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of the multitargeted antifolate LY231514 (ALIMTA, MTA, pemetrexed disodium) in patients with advanced pancreatic cancer. Miller, KD., Picus, J., Blanke, C., et al.[2020]

Pemetrexed is a multitargeted antifolate that effectively inhibits key enzymes involved in cancer cell growth and is active against various solid tumors, including non-small-cell lung cancer and ovarian cancer.

A recent randomized trial found that administering pemetrexed followed by gemcitabine on specific days every 21 days resulted in the best efficacy and lowest toxicity, highlighting an optimized treatment sequence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical studies of pemetrexed and gemcitabine combinations. Adjei, AA.[2022]

In a meta-analysis of 486 patients with advanced non-squamous non-small cell lung cancer, the pemetrexed plus carboplatin regimen at 5 mg/min•mL (PCb5) showed a significantly lower incidence of treatment-emergent adverse events (TEAEs) compared to the 6 mg/min•mL (PCb6) regimen, including less thrombocytopenia, anemia, and fatigue.

Despite the differences in safety profiles, both PCb5 and PCb6 regimens demonstrated similar efficacy outcomes in terms of overall survival and progression-free survival, indicating that PCb5 may be a safer option without compromising treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis of pemetrexed plus carboplatin doublet safety profile in first-line non-squamous non-small cell lung cancer studies. Okamoto, I., Schuette, WH., Stinchcombe, TE., et al.[2018]

In a phase II trial involving 34 elderly patients (median age 77) with non-squamous non-small cell lung cancer, the combination of carboplatin and pemetrexed followed by pemetrexed maintenance therapy resulted in a 1-year overall survival rate of 58% and a median overall survival of 20.5 months.

The treatment was generally well tolerated, although there were notable grade ≥3 adverse events, including neutropenia (55.9%) and infections (23.5%), indicating that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of pemetrexed plus carboplatin followed by maintenance pemetrexed as first-line chemotherapy for elderly patients with advanced non-squamous non-small cell lung cancer. Tamiya, M., Tamiya, A., Kaneda, H., et al.[2022]

Pemetrexed shows promising efficacy in treating gastrointestinal tumors, with a 15-17% response rate in metastatic colorectal cancer and a 6% response rate in advanced pancreatic cancer, comparable to standard treatments like gemcitabine.

The drug has a generally mild side effect profile, especially when combined with folate supplementation and dexamethasone, indicating potential for further studies to explore its role in combination therapies for colorectal, pancreatic, and gastric cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed in patients with gastrointestinal carcinoma. de Gramont, A., Kindler, HL.[2019]

In a study of 200 patients with untreated advanced gastric carcinoma, the PELF treatment regimen showed a significantly higher complete response rate (13%) compared to the FAMTX regimen (2%), indicating greater efficacy in treating this type of cancer.

The objective response rates were also better for PELF (39%) versus FAMTX (22%), suggesting that PELF is a more effective treatment option, although the survival rate differences were not statistically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin, epirubicin, leucovorin and 5-fluorouracil (PELF) is more active than 5-fluorouracil, doxorubicin and methotrexate (FAMTX) in advanced gastric carcinoma. Cocconi, G., Carlini, P., Gamboni, A., et al.[2022]

In a phase II study involving 62 elderly patients (average age 76.4 years) with advanced non-small cell lung cancer (NSCLC), the combination of pemetrexed and carboplatin achieved an objective tumor response rate of 28.6%, indicating its potential efficacy in this population.

The treatment was generally well-tolerated, although neutropenia was the most common severe side effect, affecting over half of the patients, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed and carboplatin, an active option in first-line treatment of elderly patients with advanced non-small cell lung cancer (NSCLC): a phase II trial. Gervais, R., Robinet, G., Clément-Duchêne, C., et al.[2015]

The combination of carboplatin and pemetrexed was found to be safe and well tolerated in a study of 20 patients with platinum-sensitive recurrent ovarian cancer, with no serious adverse events related to the therapy.

The treatment showed promising efficacy, with a complete response rate of 63.2% and a partial response rate of 21.1%, indicating that this combination could be a viable option for improving outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase-I trial of pemetrexed plus carboplatin in recurrent ovarian cancer. Sehouli, J., Camara, O., Mahner, S., et al.[2015]

In a study involving 361 patients with advanced nonsquamous non-small-cell lung cancer, the combination of pemetrexed and carboplatin (Pem+Cb) did not show a significant advantage in progression-free survival without grade 4 toxicity compared to paclitaxel, carboplatin, and bevacizumab (Pac+Cb+Bev).

While both treatment regimens were generally well tolerated, Pem+Cb was associated with higher rates of grade 3/4 anemia and thrombocytopenia, whereas Pac+Cb+Bev had more cases of grade 3/4 neutropenia and alopecia, indicating differing toxicity profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PRONOUNCE: randomized, open-label, phase III study of first-line pemetrexed + carboplatin followed by maintenance pemetrexed versus paclitaxel + carboplatin + bevacizumab followed by maintenance bevacizumab in patients ith advanced nonsquamous non-small-cell lung cancer. Zinner, RG., Obasaju, CK., Spigel, DR., et al.[2022]

Citations

1. arcusbio.com arcusbio.com/wp-content/uploads/2025/10/AB598-PKPD-ENA_poster-draft_8Oct2025.pdf

RESULTS AB598 is under investigation in a first-in-human, multicenter, non- randomized, open-label phase 1 study in patients with advanced solid tumors. (NCT05891171).

2. aacrjournals.org aacrjournals.org/mct/article/24/10_Supplement/C076/766567/Abstract-C076-Clinical-pharmacokinetic

Abstract C076: Clinical pharmacokinetic/pharmacodynamic ... AB598 is under investigation in a first-in-human, multicenter, non-randomized, open-label phase 1 study in patients with advanced solid tumors ( ...

3. aacrjournals.org aacrjournals.org/mct/article/23/10/1471/748617/Characterization-of-AB598-a-CD39-Enzymatic

Characterization of AB598, a CD39 Enzymatic Inhibitory ... AB598 is a CD39 inhibitory antibody being pursued for the treatment of solid tumors in combination with chemotherapy and immunotherapy.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38797955/

Characterization of AB598, a CD39 Enzymatic Inhibitory ... AB598 is a CD39 inhibitory antibody being pursued for the treatment of solid tumors in combination with chemotherapy and immunotherapy.

5. jitc.bmj.com jitc.bmj.com/content/11/Suppl_1/A883

787 AB598, a CD39 inhibitory antibody, promotes immune ... Methods The effectiveness of AB598 in combating tumors with an intact immune system was assessed utilizing a human CD39 knock-in (hCD39KI) ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05891171?term=AREA%5BBasicSearch%5D(AREA%5BConditionSearch%5D(%22Cervical%20Cancer%22)%20AND%20AREA%5BInterventionSearch%5D(%22micronutrients%22))&rank=8

Study of AB598 Monotherapy and Combination Therapy in ... Also called a data safety and monitoring board, or DSMB. Early Phase 1 (formerly listed as Phase 0). A phase of research used to describe exploratory trials ...

7. careacross.com careacross.com/clinical-trials/trial/NCT05891171

Study of AB598 Monotherapy and Combination Therapy in ... Summary: The primary purpose of this study is to assess the safety and tolerability of AB598 when taken alone, and in combination with zimberelimab and standard ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05891171

NCT05891171 | Study of AB598 Monotherapy and ... The primary purpose of this study is to assess the safety and tolerability of AB598 in participants with advanced malignancies. Official Title. A Phase 1/1b ...

9. bcan.org bcan.org/clinicaltrials/ab598-monotherapy-and-combination-therapy-in-participants-with-advanced-cancers/

AB598 Monotherapy and Combination Therapy in ... The primary purpose of this study is to assess the safety and tolerability of AB598 in participants with advanced malignancies.