Domvanalimab + Zimberelimab vs Pembrolizumab for Lung Cancer

(ARC-10 Trial)

Not currently recruiting at 543 trial locations

Overseen By Medical Director

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Arcus Biosciences, Inc.

Must not be taking: Corticosteroids, Immunosuppressive drugs

Disqualifiers: Autoimmune disease, Prior malignancy, 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: 12-24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines new treatments for individuals with advanced non-small cell lung cancer (NSCLC) who exhibit high levels of the protein PD-L1. The study aims to determine the effectiveness of combining two drugs, zimberelimab and domvanalimab, compared to the standard treatment, pembrolizumab. Participants will receive various combinations of these drugs, and researchers seek to identify the most effective option. This trial suits those with untreated NSCLC and documented high PD-L1 expression. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on medications for autoimmune diseases or have received live vaccines recently, you may need to discuss this with the trial team.

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

Research has shown that zimberelimab, when used alone, is generally safe and well-tolerated, meaning it typically does not cause unexpected side effects. Studies have not identified any new safety issues with zimberelimab, which reassures those considering it.

Early results for the combination of domvanalimab and zimberelimab are also positive. Initial research indicates that the combination is safe, with no new safety concerns, suggesting patients generally tolerate it well.

In this trial, the safety of these treatments remains under study, but current data is reassuring. Both treatments appear safe based on existing evidence, with no major unexpected side effects reported. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments involving domvanalimab and zimberelimab for lung cancer because they bring a fresh approach compared to current options. Most treatments, like pembrolizumab, work by targeting the PD-1/PD-L1 pathway to boost the immune system's ability to fight cancer. However, domvanalimab and zimberelimab go a step further by also targeting the TIGIT pathway, potentially enhancing the immune response even more. This dual-targeting strategy could offer a more comprehensive attack on cancer cells, providing hope for improved outcomes. Additionally, these treatments are administered intravenously, similar to existing therapies, ensuring they are accessible and easy to integrate into current treatment protocols.

What evidence suggests that this trial's treatments could be effective for lung cancer?

Research shows that combining domvanalimab with zimberelimab yields promising results for treating lung cancer. In this trial, one group will receive the domvanalimab and zimberelimab combination, which studies have shown reduces the risk of death by 36% compared to zimberelimab alone. This suggests that the combination might be more effective than zimberelimab, which is being tested as a monotherapy in another group of this trial. Although zimberelimab alone has shown positive results in the past, the combination appears to offer a greater chance of survival. The combination works by blocking certain proteins that cancer cells use to evade the immune system, potentially helping the body attack the cancer more effectively. ^{1 6 7 8 9}

Who Is on the Research Team?

Medical Director

Principal Investigator

Arcus Biosciences, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with untreated, advanced non-small cell lung cancer that shows high PD-L1 expression. They must have good organ function and at least one measurable tumor lesion. Those with stable brain metastases may qualify, but not if they have autoimmune diseases requiring recent treatment or other active cancers within the last two years.

Inclusion Criteria

My advanced lung cancer has high PD-L1 levels, confirmed by a specific test.

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

My brain metastases are stable, and I haven't needed steroids for them in over 14 days.

Exclusion Criteria

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

I have been treated with drugs targeting the immune system.

I haven't had any cancer except for minor ones like skin or superficial bladder cancer in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive zimberelimab (AB122) combined with domvanalimab (AB154) or other specified treatments by IV infusion

12-24 weeks

Regular visits for IV infusions

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Domvanalimab
• Paclitaxel
• Pembrolizumab
• Pemetrexed
• Zimberelimab

Trial Overview The study compares a new combination of drugs (Domvanalimab and Zimberelimab) against an established drug (Pembrolizumab), all alongside standard chemotherapy agents like Carboplatin and Paclitaxel to treat lung cancer. It's designed to see which regimen works better in first-line therapy.

How Is the Trial Designed?

Group I: Arm D - Study Part 2 (Domvanalimab + Zimberelimab Combination Therapy) Experimental Treatment 2 Interventions

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

Group II: Arm C - Study Part 1 (Domvanalimab + Zimberelimab Combination Therapy) Experimental Treatment 2 Interventions

Participants will receive zimberelimab in combination with AB154 by IV infusion.

Group III: Arm B - Study Part 1 (Zimberelimab Monotherapy) Experimental Treatment 1 Intervention

Participants will receive zimberelimab monotherapy by IV infusion.

Group IV: Arm A - Study Part 1 (Platinum-based Chemotherapy) Active Control 3 Interventions

Participants will receive carboplatin, pemetrexed, and paclitaxel by intravenous (IV) infusion.

Group V: Arm E - Study Part 2 (Pembrolizumab) Active Control 1 Intervention

Participants will receive pembrolizumab by IV infusion.

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

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

Published Research Related to This Trial

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In a real-life study of 121 patients with advanced non-squamous non-small cell lung cancer, the combination of pembrolizumab and chemotherapy resulted in a median progression-free survival of 9 months and overall survival of 20.6 months, demonstrating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with manageable side effects; however, 17.5% of patients experienced grade 3-4 adverse events, and there were two treatment-related deaths, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). Renaud, E., Ricordel, C., Corre, R., et al.[2023]

In patients with metastatic non-small-cell lung cancer (NSCLC) expressing PD-L1 in ≥50% of tumor cells, pembrolizumab significantly improves progression-free and overall survival compared to traditional platinum-based chemotherapy.

Combining pembrolizumab with standard chemotherapy (pemetrexed and a platinum drug) enhances survival outcomes regardless of PD-L1 expression, indicating a broader efficacy of this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined Checkpoint Inhibition and Chemotherapy: New Era of 1st-Line Treatment for Non-Small-Cell Lung Cancer. Wang, C., Kulkarni, P., Salgia, R.[2020]

In the phase III KEYNOTE-189 study, pembrolizumab combined with pemetrexed and platinum-based chemotherapy significantly improved overall survival (OS) and progression-free survival (PFS) in patients with untreated metastatic nonsquamous non-small-cell lung cancer, with a hazard ratio of 0.56 for OS and 0.49 for PFS after a median follow-up of 31 months.

The treatment was associated with a high objective response rate (ORR) of 48.3% compared to 19.9% for the placebo group, and among patients who completed 35 cycles of pembrolizumab, the ORR was even higher at 85.7%, indicating strong efficacy with manageable toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed plus platinum with or without pembrolizumab in patients with previously untreated metastatic nonsquamous NSCLC: protocol-specified final analysis from KEYNOTE-189. Rodríguez-Abreu, D., Powell, SF., Hochmair, MJ., et al.[2022]

In the KEYNOTE-189 study, first-line treatment with pembrolizumab combined with pemetrexed-platinum significantly improved overall survival (OS) to a median of 22.0 months compared to 10.7 months for the placebo group, indicating a strong efficacy in treating metastatic nonsquamous non-small-cell lung cancer (NSCLC).

The combination therapy also resulted in a median progression-free survival (PFS) of 9.0 months versus 4.9 months for placebo, with benefits observed regardless of tumor PD-L1 expression or the presence of liver/brain metastases, while maintaining a similar incidence of serious adverse events between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non-Small-Cell Lung Cancer. Gadgeel, S., Rodríguez-Abreu, D., Speranza, G., et al.[2021]

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]

In a study involving 812 patients with malignant pleural mesothelioma (MPM), single-agent pemetrexed showed promising efficacy, with a median time to progressive disease of 6.0 months for chemonaïve patients and an overall response rate of 10.5%.

The treatment was well-tolerated, exhibiting mild hematologic toxicity, primarily neutropenia, in less than 18% of patients, indicating a favorable safety profile for pemetrexed in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-agent pemetrexed for chemonaïve and pretreated patients with malignant pleural mesothelioma: results of an International Expanded Access Program. Taylor, P., Castagneto, B., Dark, G., et al.[2015]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04736173

NCT04736173 | Study Evaluating Effectiveness and Safety ... This is a phase 2 study to evaluate zimberelimab (AB122) combined with domvanalimab (AB154) in front-line, PD-L1-high, locally advanced or metastatic ...

2. investors.arcusbio.com investors.arcusbio.com/investors-and-media/press-releases/press-release-details/2024/Arcus-Biosciences-Announces-that-Domvanalimab-Plus-Zimberelimab-Improved-Overall-Survival-in-ARC-10-a-Randomized-Study-in-Patients-with-PD-L1-High-Non-Small-Cell-Lung-Cancer/default.aspx

Press Release Details - Investors & Media - Arcus Biosciences Domvanalimab plus zimberelimab demonstrated a meaningful improvement in overall survival compared to zimberelimab alone, with a 36% reduction in risk of death.

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-04927

Study to Evaluate Monotherapy and Combination ... This randomized phase 2 open-label study will evaluate the safety and efficacy of zimberelimab (AB122) monotherapy, domvanalimab (AB154) in combination with ...

4. cancertherapyadvisor.com cancertherapyadvisor.com/home/cancer-topics/lung-cancer/zimberelimab-domvanalimab-etrumadenant-metastatic-nsclc/

Zimberelimab, Domvanalimab, and Etrumadenant for ... Title: A pilot study to evaluate the safety and efficacy of zimberelimab (AB122) in combination with domvanalimab (AB154) and etrumadenant ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04262856

NCT04262856 | Study to Evaluate Monotherapy and ... This randomized phase 2 open-label study will evaluate the safety and efficacy of zimberelimab (AB122) monotherapy, domvanalimab (AB154) in combination with ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04791839

Study Details | NCT04791839 | Safety and Efficacy of ... Safety and Efficacy of Zimberelimab (AB122) in Combination With Domvanalimab (AB154) and Etrumadenant (AB928) in Patients With Previously Treated Non-Small ...

7. clinical-lung-cancer.com clinical-lung-cancer.com/article/S1525-7304(23)00267-X/abstract

A Phase III Randomized Study of Domvanalimab and ... The STAR-121 (NCT05502237) phase III, global, randomized, open-label study will investigate first-line domvanalimab (anti-TIGIT) and zimberelimab (anti–PD-1) ...

8. investors.arcusbio.com investors.arcusbio.com/investors-and-media/press-releases/press-release-details/2021/Anti-TIGIT-Domvanalimab-Based-Combinations-Showed-Encouraging-Clinical-Activity-in-People-with-Metastatic-PDL1-High-Non-Small-Cell-Lung-Cancer-at-First-Interim-Analysis-of-Arcus-Biosciences-Randomized-Phase-2-ARC-7-Study/default.aspx

Anti-TIGIT Domvanalimab-Based Combinations Showed ... Anti-TIGIT Domvanalimab-Based Combinations Showed Encouraging Clinical Activity in People with Metastatic, PDL1-High Non-Small Cell Lung Cancer ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S152573042300267X

STAR-121: A Phase III Randomized Study of ... The STAR-121 (NCT05502237) phase III, global, randomized, open-label study will investigate first-line domvanalimab (anti-TIGIT) and zimberelimab (anti–PD-1) ...