The U.S. Food and Drug Administration (FDA) has granted the designation of breakthrough therapy to a combination of tiragolumab, a novel immunotherapy developed by Genentech, plus Tecentriq (atezolizumab) for the treatment of metastatic non-small cell lung cancer (NSCLC).
The designation is intended to accelerate the development and review of medications that may be superior to existing therapies at treating serious life-threatening conditions. This one covers using the combination therapy as a first-line treatment for people whose tumors contain high levels of the PD-L1 protein and harbor no mutations in the EGFR or ALK genes.
With this decision, tiragolumab is the first inhibitor of TIGIT, a protein known to suppress the activity of the immune system, and the 37th in Genentech’s portfolio to receive this designation.
“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,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Genentech, said in a press release.
“We look forward to advancing our tiragolumab development program, which includes chemotherapy-free combinations and trials in early stages of disease across multiple cancer types with high unmet need,” Garraway said.
The FDA’s designation was based on promising safety and efficacy data from the CITYSCAPE Phase 2 clinical trial (NCT03563716), the first randomized study to investigate the therapeutic potential of an anti-TIGIT antibody.
CITYSCAPE is one of the trials exploring the rationale of combining tiragolumab with Tecentriq, an antibody-based immunotherapy also developed by Genentech that inhibits PD-L1, a protein produced by cancer cells to promote immune evasion. By simultaneously blocking TIGIT and PD-L1, the tiragolumab-Tecentriq combo is expected to boost the body’s immune response against tumors.
In CITYSCAPE, 135 patients with locally advanced or metastatic NSCLC were assigned randomly to receive first-line treatment with either the tiragolumab-Tecentriq combination, or Tecentriq alone, every three weeks until disease progression or loss of clinical benefit.
The main goals of the study are to assess if the combination therapy is superior to Tecentriq at increasing the proportion of patients responding to treatment and at extending life without disease progression.
Data presented at the American Society of Clinical Oncology 2020 Virtual Scientific Program, showed that after a mean follow-up of 10.9 months, a higher percentage of patients treated with the combination therapy had responded to treatment (37% vs. 21%), and that the combination lowered the risk of disease worsening or death by 42%, compared with Tecentriq alone.
An exploratory analysis showed that the benefits were even better in a subset of patients whose tumors contained high levels of the PD-L1 protein. In this population, the percentage of patients responding to the combination treatment was nearly three times higher than with Tecentriq alone (66% vs. 24%).
Additionally, in this subgroup of patients, at least half of those receiving the combination therapy were alive and without signs of disease progression at the time of the analysis, while those given Tecentriq had died or progressed within a median of four months. This represented a 70% reduction in the risk of death or disease progression.
Safety assessments indicated the combination therapy was well-tolerated. The incidence of severe side effects was identical in patients treated with the tiragolumab-Tecentriq combo (48%) and in those given Tecentriq alone (44%).
Genentech is now planning to present additional biomarker data from CITYSCAPE at the upcoming IASLC 2020 World Conference on Lung Cancer, to be held virtually Jan. 28–31.
In addition to CITYSCAPE, the company is evaluating the therapeutic potential of the combination therapy, alone or with chemotherapy agents, in other clinical trials. These include the Phase 3 SKYSCRAPER-01 (NCT04294810) and the Phase 2 SKYSCRAPER-06 (NCT04619797) trials enrolling patients with metastatic NSCLC, and the Phase 3 SKYSCRAPER-03 (NCT04513925) open-label trial enrolling patients with earlier stage 3 NSCLC.
In addition to NSCLC, Genentech is exploring the combination therapy in other types of cancer, including small cell lung cancer (SKYSCRAPER-02; NCT04256421), advanced esophageal cancer (SKYSCRAPER-07; NCT04543617), and cervical cancer (SKYSCRAPER-04; NCT04300647).
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