Anti-TIGIT Drug Fails to Lift Response Rates in Cervical Cancer Trial

Combining the novel anti-TIGIT monoclonal antibody tiragolumab with atezolizumab (Tecentriq) to treat PD-L1-positive recurrent cervical cancer didn’t improve overall response rate in the phase II SKYSCRAPER-04 trial, the results of which were presented at the International Gynecologic Cancer Society (IGCS) annual meeting.

In this exclusive MedPage Today video, Ritu Salani, MD, of the University of California Los Angeles, discusses the results from the trial.

Following is a transcript of her remarks:

This year at IGCS, I had the pleasure of presenting our data on SKYSCRAPER-04, which was a two-arm trial looking at single-agent atezolizumab or atezolizumab and tiragolumab, which is an anti-TIGIT agent, in patients with recurrent or advanced cervical cancer with PD-L1 expression.

The study was trying to capitalize on the previous data in immunotherapy in this setting where we were hoping that using two agents would help exploit the immune system further and provide better outcomes. Our results demonstrated that atezolizumab as a single agent had a response rate of approximately 15.6%, which was consistent with historical control showing that the PD-L1 agent was comparable to the PD-1 agents that had been studied previously.

The addition of tiragolumab, unfortunately, did not show a statistical benefit over the single-agent atezolizumab. However, we did note that there was a higher response rate, showing that there’s some signal, but just not enough of overcoming the immune system exhaustion.

And so this was a negative trial, but we did have some important lessons learned from this trial. One, that the PD-L1 agent was active. Two, we included patients who did not have measurable disease by RECIST criteria. And we think this may have slightly impacted our results in a negative way. And so I think it’s important that we include patients who can be really assessed best with our objective measures of response to really understand the benefit or lack of benefit of any therapy that we’re employing.

Three, I think it’s always important that we do have an independent review assessment of our therapies when it is open-label, as this study was, just to avoid bias from investigators. Because we all want to do what’s right for our patients, but sometimes the objective responses can be more affirming.

And then, lastly, I think this may close the door for TIGIT and PD-1 inhibitors in this setting, but I don’t think it closes the door for TIGITs all throughout. I think we just have to find the right combination or maybe the right cohort of patients to treat with this agent.

And so I think this is an important study, as it shows that this can be safely administered. We had very low toxicity rates, very low discontinuation rates, but it’s not the right combination in this patient population.