Roche Launches Phase III Trial of TIGIT-Based Combination Therapy for First-Line Treatment of Hepatocellular Carcinoma

On June 15, a Phase III clinical trial IMbrave152/SKYSCRAPER-14 conducted by Roche was registered on the clinicaltrials.gov website. The trial aims to evaluateAtezolizumab (PD-L1) + Bevacizumab (VEGF) + Tiragolumab (TIGIT)Safety and efficacy in patients with locally advanced or metastatic hepatocellular carcinoma (HCC) who have not received systemic treatment. Today, the clinical trial application for tiragolumab in the treatment of HCC has also been approved in China.

The study plans to enroll 650 adult patients who are not suitable for surgery or local treatment. It is expected to start on July 31 this year and be completed on September 1, 2026. The primary endpoints of the study are investigator-assessed progression-free survival (PFS) and overall survival (OS).

On May 26 this year, Roche announced the results of the Phase Ib/II Morpheus-Liver study investigating the triplet therapy as a first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC) at the ASCO conference. As of November 28, 2022, the study enrolled a total of 58 uHCC patients, including 40 patients treated with atezolizumab + bevacizumab + tiragolumab and 18 patients treated with atezolizumab + bevacizumab.

The results showed that the confirmed objective response rate (cORR) of the triple therapy group was42.5%（17/40）, while the dual therapy group was 11.1% (2/18); the median PFS for the triple therapy group was11.1 months, while the dual-therapy group was 4.2 months,The risk ratio is 0.42.In addition, the triple therapy also showed good efficacy in both PD-L1+ and PD-L1- patient subgroups.

Morpheus-Liver Study Results (Source: ASCO 2023)

In terms of safety, the proportion of patients experiencing grade 3/4 treatment-related adverse events (TRAEs) was similar between the triplet therapy group and the doublet therapy group (27.5% vs. 33.3%), and the proportion of patients discontinuing treatment due to adverse events (AEs) was also comparable (22.5% vs. 22.2%).

After the data was released, Roche's stock price surged 14% in after-hours trading. The results also boosted industry confidence in the drugability of the TIGIT target, reflected by rising stock prices of multiple Biotech companies with a focus on the TIGIT target. Arcus Biosciences, which has two TIGIT monoclonal antibodies, saw its stock rise 26% in after-hours trading. iTeos Therapeutics, which has one TIGIT monoclonal antibody, rose 30% in after-hours trading. Compugen, which has one TIGIT bispecific antibody and one TIGIT monoclonal antibody, increased by 10% in after-hours trading.

Previously, Roche had conducted multiple explorations into the efficacy of tiragolumab, initiating a Phase III clinical trial for both non-small cell lung cancer and small cell lung cancer. However, both studies ended in failure (see: ).

Merck also encountered setbacks on the TIGIT target. On March 16 this year, Merck announced that the Phase II KeyVibe-002 study of the PD-1/TIGIT compound MK-7684A for the treatment of metastatic non-small cell lung cancer did not meet the primary endpoint of PFS.

However, the setbacks of the two major pharmaceutical giants on the TIGIT target have not dampened the enthusiasm for TIGIT research. Several pharmaceutical companies are still advancing the clinical development of TIGIT antibody drugs. Currently, there are four TIGIT-targeted drugs in Phase III studies globally: tiragolumab (Roche), vibostolimab (the TIGIT component in MK-7684A, Merck), domvanalimab (Gilead/Arcus Biosciences/Taiho Pharmaceutical), and ociperlimab (BeiGene).

Source: PharmaCube ASCO Opportunity Analysis PPT

Merck is conducting five global Phase III clinical trials of MK-7684A, challenging drugs including durvalumab, pembrolizumab, and atezolizumab; Gilead/Arcus Biosciences has also launched four global Phase III clinical trials of domvanalimab, targeting durvalumab, pembrolizumab, and nivolumab; BeiGene has initiated two global Phase III clinical trials of ociperlimab, also challenging durvalumab and pembrolizumab.

Among these, the Phase III study conducted by BeiGene comparing tislelizumab + ociperlimab versus pembrolizumab + placebo for the treatment of non-small cell lung cancer willTake the leadInMay 2025Completed. Whether Chinese pharmaceutical companies can catch up later on the TIGIT target is also quite an interesting thing to watch.

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