Combination Immunotherapy + Chemotherapy for Gastric Cancer

(STAR-221 Trial)

Recruiting at 305 trial locations

Overseen By Medical Director

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Arcus Biosciences, Inc.

Disqualifiers: Cardiovascular disease, CNS metastases, others

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

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: 2

Duration: 12-24 weeks

1040 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

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 combination immunotherapy and chemotherapy for gastric cancer?

Research shows that combinations like capecitabine plus oxaliplatin (XELOX) and 5-fluorouracil with leucovorin and oxaliplatin (FOLFOXs) are effective in treating advanced gastric cancer. These studies suggest that similar drug combinations can be beneficial for patients with this condition. ^{1 2 3 4 5}

What safety data exists for the combination of immunotherapy and chemotherapy in gastric cancer?

The combination of capecitabine and oxaliplatin (XELOX) has been studied for safety in patients with advanced gastric cancer, showing it is generally safe, though side effects like nausea, diarrhea, and low blood cell counts can occur. ^{1 2 6 7 8}

What makes the combination immunotherapy and chemotherapy treatment for gastric cancer unique?

This treatment is unique because it combines immunotherapy drugs like Domvanalimab and Zimberelimab with chemotherapy agents such as Capecitabine and Oxaliplatin, potentially enhancing the immune system's ability to fight cancer while also directly targeting cancer cells. This combination approach is novel compared to traditional chemotherapy regimens, which typically do not include immunotherapy components. ^{2 4 5 9 10}

What is the purpose of this trial?

This trial is testing a new combination of drugs to help the immune system fight advanced stomach and esophagus cancers. It compares two new drugs plus chemotherapy against an existing drug plus chemotherapy to see which works better.

Research Team

Medical Director

Principal Investigator

Arcus Biosciences

Eligibility Criteria

This trial is for adults with advanced gastric, GEJ, or esophageal adenocarcinoma that can't be surgically removed and has spread. Participants must have a good performance status (able to carry out daily activities), at least one measurable lesion, and no prior treatments for this cancer stage.

Inclusion Criteria

At least one measurable target lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

My cancer is in the stomach, GEJ, or esophagus and cannot be surgically removed.

I am fully active or can carry out light work.

Exclusion Criteria

I do not have any health conditions that would make the study treatment dangerous for me.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Domvanalimab, Zimberelimab, and chemotherapy or Nivolumab and chemotherapy

12-24 weeks

Visits every 2-4 weeks depending on treatment regimen

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• Capecitabine
• Domvanalimab
• Fluorouracil
• Leucovorin
• Oxaliplatin
• Zimberelimab

Trial Overview The study tests new drugs Domvanalimab (TIGIT inhibitor) and Zimberelimab (PD-1 inhibitor) with chemotherapy against Nivolumab (another PD-1 inhibitor) with chemo in first-line treatment. It's randomized, meaning patients are assigned to groups by chance.

Participant Groups

Group I: Domvanalimab + Zimberelimab + FOLFOX/CAPOX (PI Choice) Experimental Treatment 6 Interventions

Participants in this arm will receive Domvanalimab and zimberelimab doses once every 4 weeks (Q4W) in addition to chemotherapy with FOLFOX (oxaliplatin, leucovorin, fluorouracil) once every 2 weeks (Q2W) or Domvanalimab and zimberelimab once every 3 weeks (Q3W) in addition to chemotherapy with CAPOX (capecitabine and oxaliplatin) Q3W.

Group II: Nivolumab + FOLFOX/CAPOX (PI Choice) Active Control 5 Interventions

Participants in this arm will receive Nivolumab Q2W and FOLFOX Q2W or Nivolumab Q3W + CAPOX Q3W.

Capecitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in United States as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Canada as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Japan as Xeloda for:

• Colorectal cancer
• Breast cancer

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

Gilead Sciences

Industry Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

Findings from Research

The study compared the efficacy and safety of two chemotherapy regimens, XELOX and FOLFOXs, in 1585 patients with advanced gastric cancer, but found no significant difference in overall response rate or clinical benefit rate between the two treatments.

XELOX was associated with lower risks of nausea, stomatitis, diarrhea, and alopecia compared to FOLFOXs, but had a higher risk of hand-foot syndrome, suggesting it may be a safer option despite similar efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine plus oxaliplatin (XELOX) compared with 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOXs) in advanced gastric cancer: meta-analysis of randomized controlled trials. Xu, HB., Huang, F., Su, R., et al.[2022]

The XELOX regimen, combining oxaliplatin and capecitabine, demonstrated a 41.5% overall response rate in 41 patients with advanced or recurrent gastric cancer, indicating its efficacy in this challenging condition.

The treatment was associated with manageable toxicity, with only a few patients experiencing severe side effects, such as grade 3-4 neural toxicity and hematological issues, suggesting it is a viable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Preliminary study of XELOX regimen as the first-line chemotherapy in advanced or recurrent gastric cancer]. Min, N., He, BF., Zhang, LS., et al.[2020]

In a phase II trial involving 63 patients with advanced gastric cancer, the combination of oxaliplatin, irinotecan, and fluorouracil/folinic acid showed a response rate of 33%, indicating it is an effective treatment option for this condition.

The treatment was generally well-tolerated, with manageable side effects; however, significant toxicities included neutropenia in 59% of patients and neurotoxicity in 33%, highlighting the need for monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxaliplatin, irinotecan, and fluorouracil/folinic acid in advanced gastric cancer: a multicenter phase II trial of the Southern Italy Cooperative Oncology Group. Comella, P., Lorusso, V., Maiorino, L., et al.[2018]

S-1, an oral chemotherapy drug combining tegafur with modulators, has shown advantages over standard 5-FU-based treatments for gastric cancer in large Phase III studies, making it a recommended option in treatment guidelines.

S-1, either alone or in combination with cisplatin, is non-inferior to traditional 5-FU regimens while offering greater convenience and reduced toxicity, highlighting its potential for higher efficacy in treating gastrointestinal cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

S-1 for the treatment of gastrointestinal cancer. Satoh, T., Sakata, Y.[2022]

Capecitabine, an oral medication, showed at least equivalent efficacy to intravenous 5-FU plus leucovorin in treating metastatic colorectal cancer, with an overall response rate of 18.9% compared to 15.0% for 5-FU/LV among 602 patients.

Capecitabine had a more favorable safety profile, resulting in significantly lower rates of stomatitis and neutropenia, while being associated with a higher incidence of hand-foot syndrome, making it a convenient and effective alternative to traditional IV treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. Van Cutsem, E., Twelves, C., Cassidy, J., et al.[2022]

In a study of 44 previously untreated patients with advanced gastric cancer, the combination of cetuximab and XELOX chemotherapy resulted in a significant overall response rate of 52.3%, with median progression-free survival of 6.5 months and overall survival of 11.8 months.

The treatment was generally safe, with most side effects being mild to moderate (grade 1 or 2), such as anemia and asthenia, and serious hematologic toxicities were rare, indicating that cetuximab combined with XELOX is a viable first-line option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective phase II study of cetuximab in combination with XELOX (capecitabine and oxaliplatin) in patients with metastatic and/or recurrent advanced gastric cancer. Kim, C., Lee, JL., Ryu, MH., et al.[2021]

In Korea, patients with advanced gastric cancer who undergo D2 resection benefit from postoperative adjuvant chemotherapy with S-1 or capecitabine plus oxaliplatin, indicating a potential effective treatment strategy in this population.

Trastuzumab is now part of the standard chemotherapy for gastric cancers that overexpress the HER2 protein, highlighting the importance of targeted therapies in improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy for advanced gastric cancer: review and update of current practices. Park, SC., Chun, HJ.[2023]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Capecitabine plus oxaliplatin (XELOX) compared with 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOXs) in advanced gastric cancer: meta-analysis of randomized controlled trials. [2022]

2. China pubmed.ncbi.nlm.nih.gov

[Preliminary study of XELOX regimen as the first-line chemotherapy in advanced or recurrent gastric cancer]. [2020]

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

Phase II study of oxaliplatin, fluorouracil, and folinic acid in locally advanced or metastatic gastric cancer patients. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Oxaliplatin, irinotecan, and fluorouracil/folinic acid in advanced gastric cancer: a multicenter phase II trial of the Southern Italy Cooperative Oncology Group. [2018]

5. England pubmed.ncbi.nlm.nih.gov

S-1 for the treatment of gastrointestinal cancer. [2022]

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

Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. [2022]

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

A prospective phase II study of cetuximab in combination with XELOX (capecitabine and oxaliplatin) in patients with metastatic and/or recurrent advanced gastric cancer. [2021]

8. Germany pubmed.ncbi.nlm.nih.gov

A multicenter phase II study of biweekly capecitabine in combination with oxaliplatin as first-line chemotherapy in patients with locally advanced or metastatic gastric cancer. [2022]

9. Korea (South) pubmed.ncbi.nlm.nih.gov

Chemotherapy for advanced gastric cancer: review and update of current practices. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Capecitabine in advanced gastric cancer. [2019]