Combination Immunotherapies for Non-Small Cell Lung Cancer

(ARC-7 Trial)

Recruiting at 87 trial locations

Overseen By Aparna Hegde, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Arcus Biosciences, Inc.

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Autoimmune disease, HIV, Hepatitis, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: Each cycle is 21 or 28 days, up to 2 years

151 Participants Needed

Trial Summary

What is the purpose of this trial?

This randomized phase 2 open-label study will evaluate the safety and efficacy of zimberelimab (AB122) monotherapy, domvanalimab (AB154) in combination with zimberelimab, and domvanalimab in combination with zimberelimab and etrumadenant (AB928) in front-line, PD-L1 positive, metastatic non-small cell lung cancer.

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 use high doses of corticosteroids or immunosuppressive drugs. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination Domvanalimab, AB 154, GS-0154, Domvanalimab, Etrumadenant, AB928, Zimberelimab, AB122 for non-small cell lung cancer?

Research shows that combining different immunotherapy drugs can improve outcomes for non-small cell lung cancer. For example, studies have found that combining drugs like pembrolizumab and ipilimumab, or using a three-drug regimen with tremelimumab and durvalumab, can extend survival and improve responses compared to chemotherapy alone. ^{1 2 3 4 5}

What safety data exists for combination immunotherapies like Domvanalimab, Etrumadenant, and Zimberelimab in humans?

The research articles reviewed do not provide specific safety data for Domvanalimab, Etrumadenant, or Zimberelimab. However, they discuss the safety of other immune checkpoint inhibitors, which generally have a favorable toxicity profile, meaning they are usually safe for human use, though they can cause immune-related adverse events (side effects related to the immune system). ^{4 6 7 8 9}

What makes the combination of Domvanalimab, Etrumadenant, and Zimberelimab unique for treating non-small cell lung cancer?

This combination therapy is unique because it involves multiple immunotherapy agents that target different pathways to enhance the immune system's ability to fight cancer, potentially offering a more comprehensive approach compared to single-agent treatments or combinations with chemotherapy. ^{1 2 3 10 11}

Research Team

Medical Director

Principal Investigator

Arcus Biosciences, Inc.

Eligibility Criteria

This trial is for adults over 18 with untreated, advanced non-small cell lung cancer showing high PD-L1 expression and no EGFR or ALK tumor mutations. Participants must be relatively healthy (ECOG score of 0 or 1) and have at least one measurable lesion. They shouldn't have had other active cancers in the last two years, recent vaccines, surgeries, certain viral infections like Hepatitis B/C or HIV, gastrointestinal issues affecting oral medication intake, or require high doses of steroids.

Inclusion Criteria

You must have at least one detectable and measurable abnormality according to specific medical guidelines.

My lung cancer is untreated, spreads, has high PD-L1, and no EGFR or ALK changes.

I am 18 years old or older.

Exclusion Criteria

I haven't had active cancer in the last 2 years, except for certain treated and cured types.

I have not received any live vaccines in the last 28 days.

I am taking high doses of steroids or medications that suppress my immune system.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive zimberelimab monotherapy, domvanalimab in combination with zimberelimab, or domvanalimab in combination with zimberelimab and etrumadenant

Each cycle is 21 or 28 days, up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

• Domvanalimab
• Etrumadenant
• Zimberelimab

Trial Overview The study tests zimberelimab alone and in combination with domvanalimab; plus a third group receives both drugs combined with etrumadenant. It's an open-label phase 2 trial where patients are randomly assigned to these treatments to assess their safety and effectiveness against metastatic lung cancer that expresses PD-L1.

Participant Groups

Group I: Arm 3 (domvanalimab, etrumadenant, and zimberelimab combination therapy) Experimental Treatment 3 Interventions

Participants will receive oral etrumadenant in combination with domvanalimab IV and zimberelimab IV infusion

Group II: Arm 2 (domvanalimab and zimberelimab combination therapy) Experimental Treatment 2 Interventions

Participants will receive domvanalimab IV in combination with zimberelimab IV infusion.

Group III: Arm 1 (zimberelimab monotherapy) Experimental Treatment 1 Intervention

Participants will receive zimberelimab as an intravenous (IV) infusion.

Who Is Running the Clinical Trial?

Arcus Biosciences, Inc.

Lead Sponsor

Trials

44

Recruited

7,500+

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

In a study involving 51 patients with advanced non-small-cell lung cancer (NSCLC) who had previously undergone multiple treatments, the combination of pembrolizumab and ipilimumab demonstrated an objective response rate of 30%, indicating some level of antitumor activity.

While the combination therapy showed potential benefits, it also resulted in significant toxicity, with 64% of patients experiencing treatment-related adverse events, highlighting the need for careful monitoring and management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in combination with ipilimumab as second-line or later therapy for advanced non-small-cell lung cancer: KEYNOTE-021 cohorts D and H. Gubens, MA., Sequist, LV., Stevenson, JP., et al.[2020]

The phase III POSEIDON trial demonstrated that a three-drug regimen combining the CTLA4 inhibitor tremelimumab, the PD-L1 inhibitor durvalumab, and chemotherapy significantly improves progression-free survival and overall survival in patients with metastatic non-small cell lung cancer compared to chemotherapy alone.

This study suggests that targeting multiple immune pathways with this combination therapy may enhance treatment effectiveness for lung cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-Drug Regimen Bests Chemo in NSCLC. [2022]

The combination of platinum-based chemotherapy and immunotherapy is now the standard treatment for patients with metastatic non-small-cell lung cancer, regardless of their programmed death ligand 1 tumor proportion score.

Clinical trials have shown that this combination therapy can lead to improved and long-lasting responses by enhancing the immune system's ability to attack tumors and reducing the immunosuppressive environment that hinders immune detection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining Immunotherapy and Chemotherapy for Non-Small Cell Lung Cancer. Judd, J., Borghaei, H.[2020]

In the Asian subpopulation with advanced non-small cell lung cancer (NSCLC) and PD-L1 expression ≥1%, patients treated with nivolumab plus ipilimumab showed significantly improved overall survival (OS) and progression-free survival (PFS) compared to those receiving chemotherapy, with a 3-year OS rate of 53% versus 37%.

The safety profile of nivolumab plus ipilimumab was manageable, with grade 3-4 treatment-related adverse events occurring in 40% of patients, similar to the 36% in the chemotherapy group, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. O'Byrne, KJ., Lee, KH., Kim, SW., et al.[2022]

Immune checkpoint inhibitors, such as Pembrolizumab, Nivolumab, and Atezolizumab, have significantly improved treatment outcomes for advanced nonsmall cell lung cancer (NSCLC), especially for patients who have progressed after chemotherapy.

A new patient-oriented algorithm has been developed to help clinicians choose the most effective and personalized treatment options for advanced NSCLC, aiming to enhance patient quality of life and survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current uses of check inhibitors in the fight against advanced and/or metastatic lung cancer: will immunotherapy overcome chemotherapy? Cetin, B., Bilgetekin, İ., Ozet, A.[2020]

Patients with metastatic non-small-cell lung cancer who developed immune-mediated adverse events (imAEs) while treated with durvalumab showed significantly improved overall survival compared to those without imAEs, indicating a potential link between imAE development and treatment efficacy.

A predictive model was created using machine learning to identify patients at higher risk of developing imAEs, which could help tailor treatment strategies and enhance patient outcomes in immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between immune-mediated adverse events and efficacy in metastatic non-small-cell lung cancer patients treated with durvalumab and tremelimumab. Dey, A., Austin, M., Kluger, HM., et al.[2022]

In a study of 184 patients with non-small cell lung cancer treated with immune checkpoint inhibitors, 26.6% developed immune-related adverse events (IRAEs), with certain factors like statin use and previous corticosteroid therapy increasing the risk of IRAEs.

Interestingly, patients who experienced IRAEs had significantly better progression-free survival (41 weeks vs. 9 weeks) and overall survival (89 weeks vs. 28 weeks), suggesting that the occurrence of IRAEs may be linked to improved treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of immune-related adverse events and outcomes in patients with NSCLC treated with immune-checkpoint inhibitors. Serino, M., Freitas, C., Martins, M., et al.[2022]

In a study of 1255 patients with metastatic non-small cell lung cancer (NSCLC), first-line treatment with nivolumab plus ipilimumab (NIVO+IPI) showed a high incidence of treatment-related adverse events (TRAEs), with 78% experiencing any-grade TRAEs and 34% experiencing severe (grade 3 or 4) TRAEs, but the treatment was generally well tolerated.

Patients who discontinued NIVO+IPI due to TRAEs still had a favorable long-term survival rate, with a 3-year overall survival of 50%, indicating that stopping treatment because of side effects did not negatively impact their long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC: A Pooled Analysis of CheckMate 227, CheckMate 568, and CheckMate 817. Paz-Ares, LG., Ciuleanu, TE., Pluzanski, A., et al.[2023]

The combination of nivolumab and ipilimumab has shown promise as a first-line treatment for previously untreated advanced non-small-cell lung cancer, as demonstrated in the Phase III CheckMate 227 study.

This study is significant because it is the first to evaluate a chemotherapy-sparing approach using dual immune checkpoint inhibition, while also considering tumor mutational burden as a biomarker for selecting suitable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus ipilimumab in non-small-cell lung cancer. Reck, M., Borghaei, H., O'Byrne, KJ.[2019]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Pembrolizumab in combination with ipilimumab as second-line or later therapy for advanced non-small-cell lung cancer: KEYNOTE-021 cohorts D and H. [2020]

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

Three-Drug Regimen Bests Chemo in NSCLC. [2022]

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

Combining Immunotherapy and Chemotherapy for Non-Small Cell Lung Cancer. [2020]

4. England pubmed.ncbi.nlm.nih.gov

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. [2022]

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

Current uses of check inhibitors in the fight against advanced and/or metastatic lung cancer: will immunotherapy overcome chemotherapy? [2020]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Association between immune-mediated adverse events and efficacy in metastatic non-small-cell lung cancer patients treated with durvalumab and tremelimumab. [2022]

7. Spain pubmed.ncbi.nlm.nih.gov

Predictors of immune-related adverse events and outcomes in patients with NSCLC treated with immune-checkpoint inhibitors. [2022]

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

Safety of First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC: A Pooled Analysis of CheckMate 227, CheckMate 568, and CheckMate 817. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitors in lung cancer: past, present and future. [2017]

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

Nivolumab plus ipilimumab in non-small-cell lung cancer. [2019]

11. China pubmed.ncbi.nlm.nih.gov

[Prospect and Current Situation of Immune Checkpoint Inhibitors in First-line Treatment in Advanced Non-small Cell Lung Cancer Patients]. [2019]