Tiragolumab Plus Atezolizumab and Bevacizumab for Patients With Hepatocellular Carcinoma

Richard Finn, MD, University of California, Los Angeles, discusses results from the phase 1b/2 MORPHEUS-Liver trial which demonstrated that the addition of tiragolumab to atezolizumab plus bevacizumab shows promise among patients with previously untreated locally advanced or unresectable hepatocellular carcinoma. 

Transcript: 

Hi there, I'm Dr Richard Finn, a medical oncologist at the Geffen School of Medicine at UCLA, in Los Angeles, and thank you for joining me today for this brief review of the MORPHEUS-Liver study. 

The first results from this multi-arm study were published just this month, in February 2025, in The Lancet Oncology. By way of background, this study is evaluating various triplet regimens in the front-line treatment of advanced liver cancer. As many of you know, atezolizumab and bevacizumab was approved in May 2020 for the treatment of advanced liver cancer based on the IMbrave150 study that showed that this regimen, of a PD-L1 antibody with a VEGF antibody, improved survival versus sorafenib and has really become a global standard of care for this population. Along with improving overall survival we saw an improvement in progression-free survival, objective response rate, and a side effect profile which was really consistent with both drugs. After that approval, it became very clear that from reading the science, not only in liver cancer but in other malignancies, how best to improve on immuno-oncology agents is not clear; what the exact best mechanism is to delay resistance, to overcome resistance is not clear. 

The MORPHEUS platform is a multi-arm study for patients with front-line advanced liver cancer and various molecules have rotated through this platform in which there's an ongoing control arm of atezolizumab and bevacizumab (atezo-bev), but patients are also randomized to novel triplets. The study we're talking about today was one of the first mature data sets to come out that showed a signal to move forward into a phase 3 study, and that looked at the monoclonal antibody to TIGIT in combination with atezo-bev, and that antibody now has a name called tiragolumab, and as many of you may or may not know, TIGIT is another important immune checkpoint involved in overcoming resistance of cancers to the immune system. 

In this study, in a 2-to-1 randomized fashion, patients receive either atezo-bev or the triplet of atezo-bev plus tiragolumab. This study actually accrued, as mentioned, about 40 patients in the combo arm, 18 patients in the control arm and we saw an objective response rate by RECIST of 42% and that is quite striking when we compare it back to the data we have from IMbrave150 where the objective response rate was 30%. The control arm in this study, which was fairly small, underperformed but still the delta in the response rate was significant. In the MORPHEUS study, the control arm had a response rate of 11%, even magnifying the benefit, but I think that is a little lower than we would've expected. Progression-free survival, another end point was improved compared to the control arm in this study, as well as historical controls. We had a progression-free survival of over 11 months with tiragolumab and atezo-bev compared to 4.2 months with atezo-bev in the MORPHEUS study or historically speaking, a control arm [progression-free survival] of 7 months from IMbrave150.

The other major end point from this study was safety, and really, we did not see any new safety signals. Patients still needed endoscopies to come on study and we saw a low incidence of high-grade bleeding events with that because of the bevacizumab, and the overall immune-related adverse events were not higher, though we did see more rash and itching with the addition of tiragolumab, which I think could be considered an on-target effect from its effects on the immune system.  

In summary, there did appear to be a signal of activity with adding tiragolumab to atezo-bev based on the objective response rate and progression-free survival. There were no real red flags for toxicity and based on that, the IMbrave152/SKYSCRAPER-14 study was launched. This was a front-line study of atezo-bev or atezo-bev and [tiragolumab] in the front-line treatment of advanced liver cancer. This study has completed accrual and we're waiting for results with 2 end points, just like in IMbrave150, and those include progression-free survival and overall survival, and the results of this study are eagerly awaited. That is a snapshot of the MORPHEUS liver study that was published in Lancet Oncology in 2025. I hope you enjoyed this overview, and we look forward to seeing the results of the phase 3 study.

Source: 

Finn RS, Ryoo BY, Hsu CH, et al. Tiragolumab in combination with atezolizumab and bevacizumab in patients with unresectable, locally advanced or metastatic hepatocellular carcinoma (MORPHEUS-Liver): A randomised, open-label, phase 1b–2, study. Lancet Oncol. Published online: January 21, 2025. doi: 10.1016/S1470-2045(24)00679-X