Genentech: Phase 3 Study of Immunotherapy in ES-SCLC Fails to Meet Co-primary Endpoint

The phase 3 SKYSCRAPER-02 study, which evaluated the investigational anti-TIGIT immunotherapy tiragolumab plus Tecentriq (atezolizumab) and chemotherapy (carboplatin and etoposide) as an initial (first-line) treatment for individuals with extensive-stage small cell lung cancer (ES-SCLC), did not meet its co-primary endpoint of progression-free survival, Roche Group subsidiary Genentech said in a statement.

The co-primary endpoint of overall survival was not met at its interim analysis and is unlikely to reach statistical significance at the planned final analysis, the company said.

Data suggest that tiragolumab plus Tecentriq and chemotherapy was well-tolerated and no new safety signals were identified when adding tiragolumab.

Data will be presented at an upcoming medical meeting, Genentech said.

“Today’s outcome is disappointing, as we had hoped to continue building on the advances of Tecentriq in extensive stage small-cell lung cancer, which remains difficult to treat. We are thankful to all the patients and health care professionals involved in the study,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Genentech, said in the statement.

“We look forward to seeing additional data from the upcoming phase 3 trial in PD-L1-high non-small cell lung cancer based on the encouraging results from the CITYSCAPE study,” he said.

Small cell lung cancer (SCLC) is the most aggressive form of any lung cancer and is characterized by rapid progression and poor survival. Tecentriq was the first cancer immunotherapy to show a survival benefit in ES-SCLC in the phase 3 IMpower133 study and was the first approved treatment option in 20 years.

The tiragolumab program continues to explore advances in multiple clinical trials to build on Tecentriq, expand into earlier stages of disease, and provide new treatment options in advanced and difficult-to-treat cancers with high unmet medical need, Genentech said.

The FDA granted tiragolumab breakthrough therapy designation in 2021 for the initial treatment of programmed death-ligand 1-high metastatic non-small cell lung cancer, based on the results of the phase 2 CITYSCAPE study, representing the only investigational anti-TIGIT therapy to receive this designation. The phase 3 SKYSCRAPER-01 trial is ongoing to confirm the CITYSCAPE results. Since 2020, Genentech has initiated 5 phase 3 trials: NSCLC (SKYSCRAPER-01, SKYSCRAPER-03), ES-SCLC (SKYSCRAPER-02), esophageal cancers (SKYSCRAPER-07, SKYSCRAPER-08), and multiple early trials in various tumor types.

SKYSCRAPER-02 is a double-blinded, global, phase 3, placebo-controlled, randomized, study evaluating tiragolumab plus Tecentriq and chemotherapy as first-line treatment versus Tecentriq and chemotherapy alone in 490 people with ES-SCLC. Co-primary endpoints are overall survival (OS) and progression-free survival (PFS) in the primary analysis set, which was all randomized patients whose cancer had not spread to the brain. Key secondary endpoints include OS and PFS in all randomized patients, as well as safety.

Reference
Genentech provides update on phase III SKYSCRAPER-02 study in extensive-stage small cell lung cancer. Genentech. News release. March 29, 2022. Accessed March 30, 2022. https://www.gene.com/media/press-releases/14947/2022-03-29/genentech-provides-update-on-phase-iii-s