Lung Cancer Drug Shows Promise: TIGIT-Targeting Antibody + Jemperli Combo Shows Significant Tumor Shrinkage | World Briefings
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Lung Cancer Drug Shows Promise: TIGIT-Targeting Antibody + Jemperli Combo Shows Significant Tumor Shrinkage

16 September, 2024 - 4:11AM
Lung Cancer Drug Shows Promise: TIGIT-Targeting Antibody + Jemperli Combo Shows Significant Tumor Shrinkage
Credit: drramon.com

A targeted immunotherapy being developed by the biotech iTeos Therapeutics and GSK delivered promising response rates in patients with a type of lung cancer, propelling the treatment into a pivotal Phase 3 trial and adding fuel to a broader debate about the validity of the target.

The companies reported that their combination of a TIGIT-targeting antibody and GSK’s Jemperli increased the percentage of patients who saw their tumors shrink versus those who received Jemperli alone, meeting the goals of the Phase 2 trial and the expectations that analysts had set for the study to be considered a success.

The promise of TIGIT

TIGIT (T-cell immunoglobulin and ITIM domain) is an immune checkpoint protein that can suppress the activity of anti-tumor T cells. This has led to a lot of interest in the development of TIGIT-targeting antibodies, which are believed to have the potential to boost the effectiveness of existing cancer immunotherapies.

The success of the Phase 2 GALAXIES-Lung 201 trial is a significant step forward for the development of TIGIT-targeting antibodies. The trial results suggest that belrestotug, the TIGIT-targeting antibody, combined with Jemperli could be an effective treatment for patients with advanced non-small cell lung cancer (NSCLC).

Belrestotug and Dostarlimab Combo Shows Promise

The trial, conducted by iTeos Therapeutics and GSK, enrolled patients with previously untreated, unresectable, locally advanced or metastatic NSCLC with high PD-L1 expression. Patients were randomized to receive either pembrolizumab (200 mg every 3 weeks), single-agent dostarlimab (500 mg every 3 weeks), or one of three combination arms with belrestotug at doses of 100 mg, 400 mg, and 1000 mg.

The results of the trial showed that the combination of belrestotug and dostarlimab resulted in a clinically meaningful improvement in objective response rate (ORR) compared to dostarlimab alone. The ORR was 63.3%, 65.6%, and 76.7% for the 100 mg, 400 mg, and 1000 mg belrestotug cohorts, respectively, compared to 37.5% for the dostarlimab monotherapy cohort.

A Deeper Look at the Data

In addition to the improved ORR, the trial also found that the belrestotug combination was associated with a larger reduction in tumor size and a greater depth of response compared to single-agent dostarlimab. The trial also found a trend of a numerically greater magnitude of decreased circulating tumor DNA (ctDNA) linked with belrestotug dosing.

Investigating the Safety Profile

While the combination therapy showed promise in efficacy, it also led to an increase in treatment-related immune-related adverse effects (TR-irAEs) compared to dostarlimab monotherapy. The most common TR-irAEs were skin and subcutaneous tissue disorders, which were generally manageable with steroids.

Next Steps

The promising results from the GALAXIES-Lung 201 trial have led to the initiation of a Phase 3 trial, GALAXIES Lung-301, to further evaluate the efficacy and safety of belrestotug in combination with dostarlimab in patients with previously treated, unresectable locally advanced or metastatic PD-L1–high NSCLC.

The Future of TIGIT

The success of the GALAXIES-Lung 201 trial adds to the growing body of evidence that TIGIT-targeting antibodies could be an important new tool in the fight against cancer. The trial results have also sparked a debate about the validity of the target, with some experts expressing skepticism about the long-term potential of TIGIT-targeting antibodies. However, the results of this trial provide a strong rationale for further research into this promising new class of drugs. The future of TIGIT remains uncertain, but this trial represents a significant step forward in the development of this novel therapy.

The results of the GALAXIES-Lung 201 trial suggest that belrestotug combined with Jemperli could be an important new treatment option for patients with advanced NSCLC. However, it is important to note that this trial is still ongoing, and more data are needed to confirm the long-term efficacy and safety of this combination therapy.

Tags:
TIGIT GSK plc European Society for Medical Oncology Non-small cell lung cancer PD-L1 Oncology lung cancer TIGIT Immunotherapy belrestotug Jemperli GSK iTeos Therapeutics ESMO GALAXIES-Lung 201 clinical trial
Kwame Osei
Kwame Osei

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