Novel Immunotherapy Combinations for Lung Cancer

Not currently recruiting at 161 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new combinations of immunotherapy drugs for individuals with non-small cell lung cancer (NSCLC) that cannot be surgically removed and has not been previously treated. The main goal is to assess the safety and effectiveness of these treatments when used together. Participants will receive different combinations of drugs such as dostarlimab (Jemperli), pembrolizumab (KEYTRUDA), and belrestotug (GSK4428859A). This trial may suit individuals with high PD-L1 protein levels in their tumors who have not received prior treatment for advanced or metastatic lung cancer. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research shows that the combination of dostarlimab and belrestotug has been tested for safety in people with high levels of PD-L1, a protein linked to cancer growth. Earlier studies found that this combination improved response rates more than dostarlimab alone, suggesting it was generally well-tolerated. Dostarlimab alone has been widely studied in other trials for various solid tumors, showing promising results with manageable side effects.

Pembrolizumab, another treatment compared in this trial, is already approved for several cancers, including non-small cell lung cancer (NSCLC). It has a well-known safety record, with side effects that are usually predictable and manageable.

Since this trial is in an early phase, the main goal is to confirm that the combination of these drugs is safe for humans. Early trials like this one help identify and understand any potential side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for lung cancer because they explore novel combinations of immunotherapy drugs that may enhance the body's immune response against cancer cells. Dostarlimab, used in combination with belrestotug and nelistotug, offers a unique approach by potentially boosting the immune system's ability to recognize and attack tumors more effectively than standard treatments like chemotherapy. Pembrolizumab, already known as a powerful monotherapy, serves as a comparator to assess how these new combinations perform in enhancing treatment outcomes. These innovative combinations could provide more effective options for patients, targeting cancer cells with greater precision and potentially improving survival rates.

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

This trial will explore various treatment arms involving novel immunotherapy combinations for lung cancer. Research has shown that dostarlimab, one of the treatments in this trial, helps patients with advanced non-small cell lung cancer (NSCLC) live longer when combined with chemotherapy. Studies suggest that dostarlimab performs as well as pembrolizumab, another treatment option in this trial, when both are used with chemotherapy for these patients. Additionally, using belrestotug with dostarlimab, as tested in some arms of this trial, improves response rates compared to dostarlimab alone in patients with high levels of PD-L1, a protein linked to cancer growth. However, adding nelistotug to this combination has not clearly extended the time patients live without their cancer worsening. Due to this mixed evidence, the development of belrestotug has been stopped. ^{1 3 5 6 7}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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, 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]

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]

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]

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]

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-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]

Citations

1. cancernetwork.com cancernetwork.com/view/dostarlimab-plus-chemo-yield-strong-survival-results-in-metastatic-nsclc

Dostarlimab Plus Chemo Yield Strong Survival Results in ... OS findings from the PERLA trial showed continued success with dostarlimab plus chemotherapy in patients with advanced non–small cell lung cancer.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04581824

NCT04581824 | Efficacy Comparison of Dostarlimab Plus ... This study aims to compare the efficacy and safety PD-1 inhibitors dostarlimab and pembrolizumab, when administered in combination with chemotherapy.

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(20)41709-0/fulltext

1399P Safety and efficacy of dostarlimab in patients (pts) ... Dostarlimab is being evaluated in pts with advanced solid tumors in the ongoing phase 1 GARNET trial (NCT02715284). Here, we present safety/efficacy data from ...

4. nature.com nature.com/articles/s41467-023-42900-4

Dostarlimab or pembrolizumab plus chemotherapy in ... Here, we show that in the PERLA study, dostarlimab plus chemotherapy has comparable efficacy to pembrolizumab plus chemotherapy as 1 L treatment ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39378565/

Patient-reported outcomes in patients with metastatic non- ... PERLA (NCT04581824) compared efficacy and safety of dostarlimab (DCT) or pembrolizumab (PCT) plus chemotherapy as first-line treatment for metastatic non-small ...

6. clinical-lung-cancer.com clinical-lung-cancer.com/article/S1525-7304(22)00115-2/fulltext

Results from Cohort E of the Phase I GARNET Trial Dostarlimab demonstrated promising antitumor activity in advanced/recurrent NSCLC that progressed following platinum-based chemotherapy, ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02715284

NCT02715284 | Study of TSR-042, an Anti-programmed ... Part 2B of the study will examine the safety and clinical activity of dostarlimab in cohorts of participants with specific types of advanced solid tumors.