Genentech Updates on Phase II/III Skyscraper-06 Study in Metastatic Non-Squamous NSCLC

Genentech, part of the Roche Group, announced the results of the Phase II/III SKYSCRAPER-06 study on July 3, 2024. This study aimed to compare the efficacy of a combination therapy involving tiragolumab and Tecentriq (atezolizumab) with chemotherapy against pembrolizumab with chemotherapy. The focus was on patients with previously untreated, locally advanced unresectable or metastatic non-squamous non-small cell lung cancer (nSq NSCLC).

Unfortunately, the study did not meet its primary endpoints. The primary analysis indicated progression-free survival (PFS) with a hazard ratio (HR) of 1.27 [95% CI: 1.02,1.57]. Additionally, the overall survival (OS) at the first interim analysis showed an HR of 1.33 [95% CI: 1.02, 1.73] but remained immature. The results signified that the combination therapy did not perform better in PFS and OS compared to the control group.

The safety profile for the combination of tiragolumab, Tecentriq, and chemotherapy was consistent with previous observations, and no new safety concerns were identified. Given these findings, Genentech decided to unblind patients and investigators and planned to halt the study. Detailed results will be communicated to investigators and health authorities and will be presented at a future medical conference.

Levi Garraway, M.D., Ph.D., the chief medical officer and head of Global Product Development at Genentech, expressed disappointment over the results. He emphasized that while the outcome was not as hoped, the insights gained would advance the understanding of the anti-TIGIT pathway and contribute to future cancer research efforts.

The SKYSCRAPER-06 study was global, randomized, placebo-controlled, and double-blinded. It involved 542 participants who were treated with the tiragolumab and Tecentriq combination and chemotherapy versus pembrolizumab and chemotherapy. The primary endpoints were overall survival (OS) and progression-free survival (PFS).

Tiragolumab is an investigational immune checkpoint inhibitor that targets TIGIT, an immune checkpoint that suppresses the body's immune response to cancer. Preclinical research suggests that tiragolumab can act as an immune amplifier when used with other cancer immunotherapies such as Tecentriq. The TIGIT pathway is distinct yet complementary to the PD-L1/PD-1 pathway, and dual blockade might help in overcoming immune suppression and restoring immune responses.

Tecentriq (atezolizumab) is a monoclonal antibody designed to bind to PD-L1, a protein expressed on tumor cells and immune cells infiltrating tumors. By inhibiting PD-L1, Tecentriq may reactivate T cells, which can attack cancer cells. It is used to treat adults with non-small cell lung cancer (NSCLC), among other conditions.

Tecentriq can cause the immune system to attack normal organs and tissues, leading to potentially severe or life-threatening complications. Patients experiencing new or worsening symptoms, such as lung, intestinal, liver, hormone gland, kidney, and skin problems, should seek medical attention immediately. Infusion reactions and complications in patients who have received stem cell transplants are also concerns. Patients may need to stop Tecentriq treatment if severe side effects occur.

Common side effects of Tecentriq when used alone include fatigue, decreased appetite, shortness of breath, cough, and nausea. When used in combination with other anti-cancer medicines for lung cancer, additional side effects such as constipation and musculoskeletal pain may occur. Tecentriq may also affect fertility in females.

Genentech, established over 40 years ago, is a pioneering biotechnology company that develops therapies for serious medical conditions. It is headquartered in South San Francisco, California, and is a member of the Roche Group.