Belrestotug + Dostarlimab for Lung Cancer

Not currently recruiting at 281 trial locations

Overseen By EU GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: GlaxoSmithKline

Must not be taking: Immune checkpoint inhibitors

Disqualifiers: EGFR mutations, ALK translocations, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of combining two drugs, belrestotug and dostarlimab, for treating a specific type of previously untreated lung cancer. It compares this combination to a standard treatment using pembrolizumab and a placebo. Suitable participants include those with advanced lung cancer that cannot be surgically removed and has not been treated with certain therapies, especially if their cancer cells show high levels of a marker called PD-L1. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that the combination of belrestotug and dostarlimab demonstrated manageable safety in earlier studies, meaning most patients did not experience severe side effects. However, another study found that the belrestotug program was stopped due to mixed results, including no clear benefit in delaying lung cancer progression. This decision suggests that while some safety concerns existed, they did not outweigh the potential benefits.

In this trial, researchers will closely monitor for any side effects to ensure that safety remains a top priority. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for lung cancer?

Researchers are excited about Belrestotug combined with Dostarlimab for lung cancer because it offers a fresh approach to treatment. Unlike traditional therapies like chemotherapy or existing immunotherapies, this combination leverages a novel mechanism of action. Belrestotug, a new active ingredient, works alongside Dostarlimab to potentially enhance the immune system's ability to target and destroy cancer cells. This innovative strategy aims to improve effectiveness over current options, potentially leading to better outcomes for patients.

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

In this trial, participants will receive either the combination of belrestotug and dostarlimab or pembrolizumab plus placebo. Research shows that combining belrestotug and dostarlimab might improve treatment response in lung cancer patients. One study found that this combination increased the number of patients who responded to treatment compared to dostarlimab alone in advanced non-small cell lung cancer (NSCLC) with high levels of PD-L1, a protein influencing cancer growth. However, the combination did not slow the cancer's growth or spread. Due to these mixed results, the development of belrestotug has been stopped. While there might be some benefit in terms of response, the overall effectiveness remains uncertain. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic non-small-cell lung cancer that has high levels of PD-L1 and hasn't been treated before. Participants must be able to undergo medical procedures and treatments as part of the study.

Inclusion Criteria

Has measurable disease (at least 1 target lesion) based on RECIST 1.1

My organs are working well.

My lung cancer is advanced and cannot be removed by surgery.

Exclusion Criteria

I have a history of lung conditions.

Has never smoked

I have been treated for an autoimmune disease 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 either belrestotug plus dostarlimab or pembrolizumab plus placebo

Up to approximately 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Belrestotug
• Dostarlimab

Trial Overview The trial tests if combining dostarlimab with belrestotug improves survival compared to pembrolizumab with a placebo in patients with specific lung cancer. It measures how long patients live without their disease getting worse and overall survival.

How Is the Trial Designed?

Group I: Dostarlimab plus belrestotug Experimental Treatment 2 Interventions

Group II: Pembrolizumab plus placebo Active Control 2 Interventions

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

Approved in European Union as Jemperli for:

• Mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer

Approved in United States as Jemperli for:

• Mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer
• Mismatch repair deficient (dMMR) recurrent or advanced solid tumors

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

The GFF MDI (glycopyrrolate/formoterol fumarate) combination inhaler demonstrated long-term safety and tolerability over 52 weeks in patients with moderate-to-very severe COPD, with no unexpected safety issues reported among 892 subjects.

Efficacy results showed that GFF MDI significantly improved lung function (measured by FEV1) and reduced the need for rescue medication compared to individual components and open-label tiotropium, indicating its effectiveness as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of glycopyrrolate/formoterol metered dose inhaler using novel Co-Suspension™ Delivery Technology in patients with chronic obstructive pulmonary disease. Hanania, NA., Tashkin, DP., Kerwin, EM., et al.[2022]

Glycopyrrolate (GLY) delivered via the eFlow closed system nebulizer is effective for maintaining treatment in chronic obstructive pulmonary disease (COPD), showing significant improvements in lung function and patient-reported outcomes based on phase 2 and phase 3 studies.

The eFlow CS nebulizer offers a rapid and efficient delivery of GLY, providing bronchodilation within 30 minutes and lasting for 12 hours, making it a suitable option for patients who may struggle with traditional inhalers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glycopyrrolate/eFlow CS: The First Nebulized Long-Acting Muscarinic Antagonist Approved to Treat Chronic Obstructive Pulmonary Disease. Pleasants, RA.[2020]

Trelegy Ellipta is a once-daily inhaler that combines three medications—fluticasone furoate (ICS), vilanterol (LABA), and umeclidinium (LAMA)—to provide effective maintenance treatment for adults with moderate to severe COPD.

This combination therapy is specifically designed for patients who do not respond adequately to a standard treatment of an ICS and a LABA, highlighting its role in enhancing management strategies for COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once-daily triple therapy inhaler for COPD. [2018]

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-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 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 a Phase I study involving 96 healthy Chinese adults, the pharmacokinetic profiles of the budesonide/glycopyrronium/formoterol fumarate (BGF MDI) and glycopyrronium/formoterol fumarate (GFF MDI) combinations were assessed, showing that budesonide's absorption increased proportionally with dose, indicating effective delivery of the medication.

All treatments were well tolerated with mild adverse events reported, and the pharmacokinetic parameters were comparable to those seen in Western and Japanese populations, suggesting that these combinations are suitable for Chinese patients with COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Tolerability of Budesonide/Glycopyrronium/Formoterol Fumarate Dihydrate and Glycopyrronium/Formoterol Fumarate Dihydrate Metered Dose Inhalers in Healthy Chinese Adults: A Randomized, Double-blind, Parallel-group Study. Chen, Q., Hu, C., Yu, H., et al.[2022]

The study involving 24 healthy volunteers found that the blend formulation of GSK961081 and fluticasone propionate (FP) increased the systemic exposure of FP and resulted in greater serum cortisol suppression compared to administering them concurrently or separately.

There was no pharmacokinetic interaction between GSK961081 and FP when given together, indicating that the combination can be safely used without affecting the absorption of either drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of GSK961081, a novel inhaled muscarinic antagonist β2 -agonist, and fluticasone propionate administered alone, concurrently and as a combination blend formulation in healthy volunteers. Norris, V., Ambery, C., Riley, T.[2018]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06472076

NCT06472076 | A Study of Belrestotug Plus Dostarlimab ... The goal of this clinical trial is to evaluate the safety and tolerability profile of dostarlimab in combination with belrestotug when compared with ...

2. onclive.com onclive.com/view/frontline-belrestotug-dostarlimab-boosts-responses-vs-dostarlimab-alone-in-pd-l1-high-nsclc

Frontline Belrestotug/Dostarlimab Boosts Responses Vs ... Treatment with belrestotug plus dostarlimab yielded a clinically meaningful improvement in ORR vs dostarlimab monotherapy in unresectable PD-L1–high NSCLC.

3. targetedonc.com targetedonc.com/view/belrestotug-program-terminated-after-mixed-phase-2-results-in-nsclc

Belrestotug Program Terminated After Mixed Phase 2 ... Belrestotug plus dostarlimab showed no progression-free survival benefit in NSCLC, leading GSK and iTeos to discontinue all development and ongoing trials.

4. lungcancerstoday.com lungcancerstoday.com/post/officials-announce-topline-results-from-galaxies-lung-201-and-halt-development-of-belrestotug

Officials Announce Topline Results From GALAXIES ... The phase 2 platform study has been assessing the combination of belrestotug plus dostarlimab in patients with previously untreated, ...

5. clinicaltrialsarena.com clinicaltrialsarena.com/news/iteos-gsk-nsclc-trial/

iTeos and GSK begin Phase III trial of NSCLC treatment ... iTeos Therapeutics and GSK have begun a Phase III trial of belrestotug plus dostarlimab for treating non-small cell lung cancer (NSCLC).

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)03874-2/fulltext

LBA52 Interim analysis of GALAXIES Lung-201 At this IA, belrestotug + dostarlimab demonstrated clinically meaningful anti-tumor activity at each dose and a manageable safety profile, supporting further ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04446351

NCT04446351 | Study of the Safety and Effectiveness ... This first-time-in-human (FTIH) study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical ...