Domvanalimab + Zimberelimab vs Pembrolizumab for Lung Cancer

(ARC-10 Trial)

Recruiting at 507 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

169 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase 2 study to evaluate zimberelimab (AB122) combined with domvanalimab (AB154) in front-line, PD-L1-high, locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC).

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.

What data supports the effectiveness of the drug combination Domvanalimab + Zimberelimab vs Pembrolizumab for Lung Cancer?

Research shows that pembrolizumab, when combined with chemotherapy drugs like pemetrexed and carboplatin, significantly improves survival in patients with advanced non-small cell lung cancer. This suggests that pembrolizumab is effective in treating this type of lung cancer, which may provide indirect support for the effectiveness of similar drug combinations. ^{1 2 3 4 5}

Is the combination of Domvanalimab + Zimberelimab vs Pembrolizumab safe for lung cancer treatment?

Pembrolizumab, when used alone or in combination with other drugs like carboplatin and pemetrexed, has been studied for safety in lung cancer patients. These studies generally show that while there are some side effects, the treatment is considered safe for use in humans. ^{1 5 6 7 8}

What makes the drug combination of Domvanalimab + Zimberelimab unique for lung cancer treatment?

The combination of Domvanalimab and Zimberelimab with chemotherapy is unique because it involves two immune checkpoint inhibitors that target different pathways, potentially enhancing the immune system's ability to fight lung cancer compared to standard treatments like pembrolizumab alone. ^{1 2 3 5 9}

Research Team

Medical Director

Principal Investigator

Arcus Biosciences, Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Arm E - Study Part 2 (Pembrolizumab) Experimental Treatment 1 Intervention

Participants will receive pembrolizumab by IV infusion.

Group II: 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 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 C - Study Part 1 (Domvanalimab + Zimberelimab Combination Therapy) Active Control 2 Interventions

Participants will receive zimberelimab in combination with AB154 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

Findings from Research

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 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 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 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 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]

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]

References

1. China 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). [2023]

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

Combined Checkpoint Inhibition and Chemotherapy: New Era of 1st-Line Treatment for Non-Small-Cell Lung Cancer. [2020]

3. United States 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. [2021]

4. England 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. [2022]

5. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

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

Single-agent pemetrexed for chemonaïve and pretreated patients with malignant pleural mesothelioma: results of an International Expanded Access Program. [2015]

7. England 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. [2018]

8. United States 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. [2022]

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

Sintilimab plus chemotherapy for first-line treatment of advanced or metastatic nonsquamous non-small-cell lung cancer: network meta-analysis. [2023]