FDA Grants Breakthrough Therapy to First Anti-TIGIT Therapy in NSCLC With High PD-L1

The FDA has granted a Breakthrough Therapy designation (BTD) to tiragolumab in combination with atezolizumab (Tecentriq) for the frontline treatment of patients with metastatic non – small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression and no EGFR or ALK genomic aberrations, announced Roche in a press release.

Tiragolumab is the first anti-TIGIT therapy to receive a BTD. The decision was based on the findings from a randomized phase 2 study known as CITYSCAPE (NCT03563716), which provided the first evidence of enhanced anti-tumor activity when targeting both immune inhibitory receptors TIGIT and PD-L1, by potentially amplifying the immune response.

“We have been researching TIGIT as a novel cancer immunotherapy target for almost 10 years, and we are pleased that the FDA has acknowledged the potential of tiragolumab to substantially improve outcomes for people with certain types of lung cancer,” said Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development, Roche, in a statement. “We look forward to advancing our tiragolumab development program, which includes chemotherapy-free combinations and trials in [the] early stages of disease across multiple cancer types with high unmet need.”

The CITYSCAPE study showed encouraging efficacy and safety findings with the combination in patients with PD-L1-positive metastatic NSCLC. This study is the first randomized trial in the anti-TIGIT field, and full results were presented during the American Society of Clinical Oncology (ASCO) 2020 Virtual Scientific Program.

These findings demonstrated the anti-TIGIT regimen induced an objective response rate (ORR) of 37% compared with 21% with atezolizumab alone. A 42% reduction in the risk of disease worsening or death was observed with the combination compared with atezolizumab alone.

An exploratory analysis indicated that patients with high levels of PD-L1, with a tumor proportion score of ≥ 50% had a clinically meaningful ORR of 66% with the combination compared with 24% with atezolizumab alone. The median progression-free survival had not been reached versus 4.11 months in the control arm (HR, 0.30; 95% CI, 0.15-0.61).

Overall, the regimen appeared generally well-tolerated. Similar rates of all grade 3 or more all-cause adverse events were observed between the 2 arms.

Data from biomarker analyses from CITYSCAPE are expected to be presented during the International Association for the Study of Lung Cancer (IASLC) 2020 World Conference on Lung Cancer, which will be hosted virtually from January 28-31, 2021.

The broad tiragolumab development program remains ongoing across a variety of different tumor types and settings, including lung, esophageal, and cervical cancers. This program builds on the benefit observed with atezolizumab while expanding into earlier stages of disease, as well as new areas of unmet need. These include the randomized studies SKYSCRAPER-01 (NCT04294810) and SKYSCRAPER-06 (NCT04619797) in metastatic NSCLC, SKYSCAPER-02 (NCT04256421) in small cell lung cancer, SKYSCRAPER-03 (NCT04513925) in stage III NSCLC, and SKYSCRAPER-07 (NCT04543617) in esophageal cancer.

Tiragolumab is also under evaluation for the treatment of patients with metastatic esophageal squamous cancer in the SKYSCRAPER-08 study (NCT04540211) and patients with cervical cancer in the SKYSCRAPER-04 study (NCT04300647). Early trials are evaluating tiragolumab in other tumor types as well.

As TIGIT and PD-L1 proteins both play a role in the suppression of the immune system, simultaneously blocking both pathways with the combination of tiragolumab and atezolizumab has the potential to increase the anti-tumor activity by enhancing the immune response to cancer cells in the body; targeting multiple immune pathways like this may have the potential to build upon prior advances in immunotherapy and expand into earlier stages of disease, as well as provide new treatment options in areas of high unmet need.

_Reference

_{Roche’s novel anti-TIGIT tiragolumab granted FDA Breakthrough Therapy Designation in combination with Tecentriq for PD-L1-high non-small cell lung cancer. News Release. January 5, 2021. Accessed January 5, 2021. https://yhoo.it/3b7c6nj}