Roche announced today that the phase II/III SKYSCRAPER-06 study evaluating tiragolumab plus Tecentriq (atezolizumab) and chemotherapy versus pembrolizumab and chemotherapy as a first-line treatment for people with previously untreated, locally advanced unresectable or metastatic non-squamous non-small cell lung cancer did not meet its primary endpoints.

The primary analysis showed a hazard ratio (HR) of 1.27 [95% CI: 1.02, 1.57] for progression-free survival (PFS), while the first interim analysis for overall survival (OS) had a HR of 1.33 [95% CI: 1.02, 1.73], which was immature. The combination of tiragolumab, Tecentriq, and chemotherapy demonstrated reduced efficacy in both PFS and OS compared to the comparator arm in the intent-to-treat population, encompassing phase II and phase III cohorts. The overall safety profile remained consistent with previous observations, with no new or unexpected findings.

As a result of these findings, Roche has decided to unblind patients and investigators and intends to halt the study. Communications will be sent to investigators, and the results will be shared with health authorities and subsequently presented at an upcoming medical meeting.

“These results are disappointing as it was our hope that this combination might yield improved outcomes for people living with metastatic non-squamous lung cancer,” said Levi Garraway, M.D., Ph.D., Chief Medical Officer and Head of Global Product Development at Roche. “We are thankful to all of the patients and healthcare professionals involved in the study, and we will leverage the learnings to inform our scientific understanding of the anti-TIGIT pathway and new avenues in cancer research.”

Roche continues to explore the potential of tiragolumab in other treatment settings and indications through ongoing phase III studies. In light of today’s results, the company will evaluate any relevant changes needed to the ongoing tiragolumab programme.

About the SKYSCRAPER-06 Study

SKYSCRAPER-06 is a global phase II/III, randomized, placebo-controlled, and double-blinded study evaluating tiragolumab plus Tecentriq (atezolizumab) and chemotherapy as an initial treatment versus pembrolizumab and chemotherapy in 542 people with non-squamous non-small cell lung cancer. The primary endpoints are overall survival (OS) and progression-free survival (PFS).

Tiragolumab is an investigational novel immune checkpoint inhibitor that selectively binds to TIGIT, a novel inhibitory immune checkpoint that suppresses the immune response to cancer. Preclinical research suggests tiragolumab acts as an immune amplifier in combination with other cancer immunotherapies like Tecentriq. The TIGIT pathway is distinct but complementary to the PD-L1/PD-1 pathway, and dual blockade with tiragolumab and Tecentriq may help overcome immune suppression and restore the immune response.

Tecentriq is a cancer immunotherapy approved for some of the most aggressive and difficult-to-treat cancers, including certain types of early-stage non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and hepatocellular carcinoma (HCC). It is also approved for various forms of metastatic NSCLC, certain types of metastatic urothelial cancer (mUC), PD-L1-positive metastatic triple-negative breast cancer (TNBC), BRAF V600 mutation-positive advanced melanoma, and alveolar soft part sarcoma (ASPS).

Tecentriq works by binding to the protein PD-L1 on tumor cells and tumor-infiltrating immune cells, blocking interactions with PD-1 and B7.1 receptors, potentially enabling T-cell activation. It is used as a combination partner with other immunotherapies, targeted therapies, and chemotherapies across a broad range of cancers. Tecentriq is available in both intravenous and subcutaneous formulations, with the subcutaneous version approved in over 40 countries.

This development underscores the challenges in advancing cancer treatment but also highlights Roche’s commitment to understanding and improving the anti-TIGIT pathway and exploring new cancer research avenues.