Lead Investigator of SKYSCRAPER-04 Notes No Statistical Significance in Cervical Cancer


The addition of a TIGIT inhibitor to a checkpoint inhibitor showed numerical improvement but did not show statistical significance in patients with recurrent cervical cancer, according to Ritu Salani, MD.

Findings from the phase 2 SKYSCRAPER-04 trial (NCT04300647), which combined tiragolumab with atezolizumab (Tecentriq), showed numerical improvement in overall response rate (ORR) in patients with PD-L1–positive recurrent cervical cancer but did not reach statistical significance, according to Ritu Salani, MD.

The confirmed ORR in the total population was 19.0% in patients who received tiragolumab plus atezolizumab compared with 15.6% in those who were treated with atezolizumab alone. Among 105 patients with PD-L1 high tumors, the ORR was 25.0% and 20.7% among those who received combination therapy and monotherapy, respectively. Of 66 patients with PD-L1 low tumors, a response was observed in 10.0% of patients who received combination therapy and 6.3% of those who received monotherapy.

In a conversation with CancerNetwork®, Salani, the Gynecologic Oncology Fellowship Director at the University of California Los Angeles Health, and the Gynecologic editorial board member for the journal ONCOLOGY®, detailed the rationale behind the study which included the thought process of PD-L1 inhibitors and TIGIT inhibitors to increase response in the study’s population.


In recurrent cervical cancer, we’ve seen that the addition of checkpoint inhibitors has benefited patients with objective response rates and duration of responses. Unlike what we’ve seen with chemotherapy, even though [checkpoint inhibitors] leave a lot to be desired, this was a huge advantage for these patients. The rationale behind the phase 2 SKYSCRAPER-04 trial was to see if we could continue to leverage the immune system by adding a TIGIT inhibitor to a checkpoint inhibitor to see if we could avoid immune system exhaustion and continue to capitalize on the benefit of the immunotherapy.

There are 2 points to this study. One, this was the first study using a single-agent checkpoint inhibitor in this controlled fashion, so in a phase 2 study. We were able to show that a PD-L1 inhibitor was comparable to what we see historically with PD-1 inhibitors. That was an important takeaway. Unfortunately, the addition of the TIGIT inhibitor wasn’t able to overcome that immune exhaustion. Although we did see numerical improvement, we weren’t able to show that this was statistically significant. The addition of a TIGIT inhibitor to a checkpoint inhibitor, in this case, atezolizumab, didn’t provide the improvement that we were hoping to see.


Salani R, Monk BJ, Kim Y, et al. Efficacy and safety results from SKYSCRAPER-04: An open-label randomized phase 2 trial of tiragolumab plus atezolizumab for PD-L1-positive recurrent cervical cancer. Presented at 2023 Annual Global Meeting of the International Gynecologic Cancer Society; November 5-7, 2023; Seoul, Korea; abstract PO002/156.

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