Novel Immunotherapy Combinations for Lung Cancer

Recruiting at 143 trial locations

Overseen By EU GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: GlaxoSmithKline

Must not be taking: Immune checkpoint inhibitors, Steroids

Disqualifiers: EGFR mutations, ALK translocations, Autoimmune disease, 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: Up to 24 months

340 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will evaluate the efficacy, safety, pharmacokinetics (PK), and pharmacodynamics (PDy) of novel immunotherapy combinations compared with immunotherapy monotherapy in participants with Programmed death ligand-1 (PD L-1) high (Tumor cells \[TC\]/ Tumor proportion score \[TPS\] \>= 50%), previously untreated, unresectable, locally advanced or metastatic non-small cell lung cancer (NSCLC). Drug name mentioned as Belrestotug, GSK4428859A, and EOS884448 are all interchangeable for the same compound. In the rest of the document, the drug will be referred to as Belrestotug.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or any immunosuppressive medication, you must stop at least 3 days before the first dose of the study drug.

What data supports the effectiveness of the drug combination including Dostarlimab and Pembrolizumab for lung cancer?

Research shows that Pembrolizumab significantly improves survival in advanced lung cancer compared to traditional chemotherapy. Additionally, Dostarlimab has shown similar effectiveness to Pembrolizumab in lung cancer, suggesting that both drugs are potent in treating this condition. ^{1 2 3 4 5}

Is the novel immunotherapy combination for lung cancer safe for humans?

The safety profiles of dostarlimab and pembrolizumab, when combined with chemotherapy, are similar and have been studied in patients with metastatic non-squamous non-small cell lung cancer, showing that they are generally safe for human use. ^{2 3 6 7 8}

What makes the drug combination of Dostarlimab, GSK4428859A, and Pembrolizumab unique for lung cancer?

This drug combination is unique because it involves novel immunotherapy agents like Dostarlimab and Pembrolizumab, which are both PD-1 inhibitors (drugs that block a protein on immune cells to help them attack cancer cells), and GSK4428859A, which may offer a new approach to treating lung cancer by potentially enhancing the immune response against tumors. ^{2 6 7 8 9}

Research Team

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Eligibility Criteria

This trial is for adults with advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) that hasn't been treated before and has high PD-L1 levels. Participants should be in good physical condition, not have had certain lung diseases or recent major surgeries, and must not be taking immunosuppressive drugs. Smokers need to have smoked more than 100 cigarettes in their lifetime.

Inclusion Criteria

The doctor can see and measure your disease using specific guidelines.

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

My lung cancer cannot be removed by surgery or cured with radiation.

Exclusion Criteria

I am currently taking medication that weakens my immune system.

I have been treated with drugs that boost the immune system.

I have brain metastases or leptomeningeal disease that is untreated or getting worse.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive novel immunotherapy combinations or monotherapy for advanced/metastatic non-small-cell lung cancer

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

• Dostarlimab
• GSK4428859A
• Pembrolizumab

Trial Overview The study tests new combinations of immunotherapy drugs Belrestotug, GSK6097608, Pembrolizumab, and Dostarlimab against monotherapy in NSCLC patients with high PD-L1 expression. It aims to see how well these treatments work and what effects they have on the body.

Participant Groups

Group I: Substudy 2A Experimental Treatment 3 Interventions

Participants will be administered with dostarlimab, fixed dose belrestotug, and fixed dose nelistotug

Group II: Substudy 1C Experimental Treatment 2 Interventions

Participants will be administered with dostarlimab in a fixed dose followed by belrestotug in a fixed dose (Dose C).

Group III: Substudy 1B Experimental Treatment 2 Interventions

Participants will be administered with dostarlimab in a fixed dose followed by belrestotug in a fixed dose (Dose B).

Group IV: Substudy 1A Experimental Treatment 2 Interventions

Participants will be administered with dostarlimab in a fixed dose followed by belrestotug in a fixed dose (Dose A).

Group V: Dostarlimab Monotherapy Experimental Treatment 1 Intervention

Participants will be administered with dostarlimab as monotherapy in a fixed dose.

Group VI: Pembrolizumab Monotherapy Active Control 1 Intervention

Participants will be administered with pembrolizumab as monotherapy in a fixed dose.

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

Approved in European Union as Jemperli for:

• Mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer
• dMMR/MSI-H recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum-containing regimen

Approved in United States as Jemperli for:

• Adults with dMMR recurrent or advanced solid tumors who have progressed on or following prior treatment and lack satisfactory alternative treatment options
• Primary advanced or recurrent dMMR endometrial cancer in combination with carboplatin and paclitaxel

Who Is Running the Clinical Trial?

GlaxoSmithKline

Lead Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

iTeos Therapeutics

Industry Sponsor

Trials

11

Recruited

2,500+

Findings from Research

In the KEYNOTE-024 study involving 305 patients with untreated advanced non-small-cell lung cancer, pembrolizumab significantly improved overall survival (OS) compared to platinum-based chemotherapy, with a median OS of 30.0 months versus 14.2 months for chemotherapy.

Pembrolizumab also had a better safety profile, with fewer treatment-related severe adverse events (31.2% for pembrolizumab vs. 53.3% for chemotherapy), indicating it is a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. Reck, M., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

Dostarlimab, an anti-PD-1 monoclonal antibody, has been shown to be equipotent to pembrolizumab in suppressing PD-1 activity, with an estimated effective concentration of 1.95 μg/ml based on data from the GARNET trial.

The recommended dosing regimen for dostarlimab is 500 mg every 3 weeks for 4 cycles, followed by 1000 mg every 6 weeks, which supports its use as a potent treatment option for patients with recurrent or advanced mismatch repair-deficient solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative analysis of PD-1 target engagement of dostarlimab and pembrolizumab in advanced solid tumors using ex vivo IL-2 stimulation data. Austin, D., Melhem, M., Gandhi, Y., et al.[2023]

In the PERLA trial involving patients with metastatic non-squamous NSCLC, the combination of dostarlimab and chemotherapy (DCT) showed a higher overall response rate (45%) compared to pembrolizumab and chemotherapy (PCT) (39%), particularly in PD-L1-positive subgroups.

Dostarlimab also demonstrated improved median progression-free survival (8.8 months) and median overall survival (19.4 months) compared to pembrolizumab (6.7 months and 15.9 months, respectively), indicating its potential as an effective first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab or pembrolizumab plus chemotherapy in previously untreated metastatic non-squamous non-small cell lung cancer: the randomized PERLA phase II trial. Lim, SM., Peters, S., Ortega Granados, AL., et al.[2023]

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]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Dostarlimab-gxly (Jemperli) has received accelerated approval from the FDA for treating adults with mismatch repair deficient recurrent or advanced endometrial cancer and solid tumors, indicating its potential effectiveness in these specific cancer types.

This approval highlights the importance of targeted therapies in oncology, particularly for patients with specific genetic markers that may influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Drug for Mismatch Repair Deficient Endometrial Cancer and Solid Tumors. Aschenbrenner, DS.[2023]

Dostarlimab (JEMPERLI) is a PD-1 monoclonal antibody that has received rapid FDA approval for treating adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer, showing promising tumor response rates.

A clinical trial (NCT04165772) reported a remarkable 100% remission rate for rectal cancer patients treated with Dostarlimab, highlighting the potential of matching tumor genetics with targeted therapies, and the trial is ongoing for other cancer types like gastric, prostate, and pancreatic cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab: A Review. Costa, B., Vale, N.[2022]

Dostarlimab is a monoclonal antibody that targets the PD-1 receptor and has been approved for treating adult patients with mismatch repair deficient recurrent or advanced endometrial cancer based on promising results from the GARNET trial.

The approval of dostarlimab in the EU and USA marks a significant milestone in cancer treatment, highlighting its potential efficacy in targeting specific cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab: First Approval. Markham, A.[2021]

Dostarlimab showed promising antitumor activity in patients with recurrent/advanced non-small cell lung cancer (NSCLC) who had progressed after platinum-based chemotherapy, achieving an immune-related objective response rate (irORR) of 26.9% across various PD-L1 expression levels.

The treatment was generally well-tolerated, with fatigue being the most common severe adverse event (4.5%), and immune-related treatment-emergent adverse events occurring in 28.4% of patients, indicating an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Dostarlimab in Patients With Recurrent/Advanced Non-small Cell Lung Cancer: Results from Cohort E of the Phase I GARNET Trial. Moreno, V., Roda, D., Pikiel, J., et al.[2023]

References

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

Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. [2022]

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

Comparative analysis of PD-1 target engagement of dostarlimab and pembrolizumab in advanced solid tumors using ex vivo IL-2 stimulation data. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Dostarlimab or pembrolizumab plus chemotherapy in previously untreated metastatic non-squamous non-small cell lung cancer: the randomized PERLA phase II trial. [2023]

4. 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]

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

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

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

New Drug for Mismatch Repair Deficient Endometrial Cancer and Solid Tumors. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Dostarlimab: A Review. [2022]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Dostarlimab: First Approval. [2021]

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

Safety and Efficacy of Dostarlimab in Patients With Recurrent/Advanced Non-small Cell Lung Cancer: Results from Cohort E of the Phase I GARNET Trial. [2023]