Findings from the phase 2 SKYSCRAPER-04 trial support dual targeting of TIGIT and PD-L1 in patients with PD-L1–positive cervical cancer, says Ritu Salani, MD.
Combining tiragolumab with atezolizumab (Tecentriq) yielded a numerical improvement in overall response rate (ORR) among patients with PD-L1–positive recurrent cervical cancer but did not reach statistical significance compared with a historical reference, according to findings from the phase 2 SKYSCRAPER-04 trial (NCT04300647) presented at the 2023 Annual Global Meeting of the International Gynecologic Cancer Society (IGCS).1
Across the overall population (n = 171), the confirmed ORR was 19.0% in patients who received tiragolumab plus atezolizumab (n = 126) compared with 15.6% in those who were treated with atezolizumab alone (n = 45). In a historical cohort of 82 patients with PD-L1–positive cervical cancer treated with pembrolizumab (Keytruda) in the phase 2 KEYNOTE-158 basket study (NCT02628067), the ORR was 14.6%.2 The improvement in ORR with tiragolumab plus atezolizumab compared with pembrolizumab did not reach statistical significance (P = .0787).
Among 105 patients with PD-L1 high tumors, investigators reported an ORR of 25.0% and 20.7% among those who received tiragolumab plus atezolizumab (n = 76) and patients treated with atezolizumab monotherapy (n = 29), respectively. Of 66 patients with PD-L1 low tumors, a response was observed in 10.0% of patients who received tiragolumab plus atezolizumab (n = 50) and 6.3% of those who received atezolizumab alone (n = 16).
In a post hoc subgroup analysis including all treated patients with measurable disease per independent review committee (IRC) assessment (n = 149), the ORR was 21.6% with the tiragolumab regimen (n = 111) and 15.8% with atezolizumab monotherapy (n = 38). Across the PD-L1 high population (n = 86), investigators highlighted an ORR of 30.2% in the tiragolumab cohort (n = 63) and 21.7% in patients who only received atezolizumab (n = 23). Of those with PD-L1 low tumors and measurable disease (n = 63), 10.4% of patients who received the combination (n = 48) and 6.7% of those treated with atezolizumab alone (n = 15) achieved an objective response.
“These data add to the accumulating evidence supporting dual targeting of TIGIT and PD-L in cervical cancer,” presenting author Ritu Salani, MD, the Gynecologic Oncology Fellowship Director at University of California Los Angeles Health and the Gynecologic editorial board member for the journal ONCOLOGY® said during the presentation.
In the SKYSCRAPER-04 trial, patients were randomly assigned 3:1 to receive atezolizumab at 1200 mg intravenously every 3 weeks with or without 600 mg of tiragolumab intravenously every 3 weeks. Patients who showed signs of unequivocal progressive disease in the atezolizumab monotherapy arm were eligible to crossover to the combination arm.
The trial’s primary end point was ORR per RECIST v1.1 criteria as assessed by an IRC. The ORR data were compared with the historical reference ORR of 14.6% in the KEYNOTE-158 study; the threshold for a statistically significant improvement was P ≤.0245. Secondary end points included progression-free survival per IRC evaluation, OS, and safety.
Patients diagnosed with recurrent or persistent cervical cancer not amenable to curative therapy who received 1 or 2 previous lines of systemic chemotherapy were able to enroll on the trial. Additional eligibility criteria included at least 1 prior line of platinum-based chemotherapy, measurable disease, and PD-L1–positive disease. Investigators stratified patients by ECOG performance status, receipt of prior radiotherapy, and disease status.
The median patient age was 49.5 years (range, 26-80) in the tiragolumab combination arm compared with 52 years (range, 27-72) in the atezolizumab monotherapy arm. Most patients in each respective arm were White (63% vs 62%), had an ECOG performance status of 0 (52% vs 51%), had measurable disease (88% vs 84%), and received prior treatment with paclitaxel (92% vs 96%).
As of the data cutoff of June 30, 2022, treatment remains ongoing in 17 patients who initiated tiragolumab and atezolizumab combination therapy. Additionally, 6 patients continue to receive atezolizumab monotherapy. Among those initially assigned to receive atezolizumab alone, 15 crossed over to the tiragolumab combination, 3 of whom continue to receive treatment.
With a data cutoff of December 8, 2021, the median PFS was 2.8 months (95% CI, 1.7-4.1) in patients who received tiragolumab plus atezolizumab and 1.9 months (95% CI, 1.5-3.0) with atezolizumab alone. The 12-month PFS rate in each respective arm was 18% and 13%. Additionally, the median OS was 11.1 months (95% CI, 9.6-14.5) and 10.6 months (95% CI, 6.9-13.8).
Any-grade adverse effects (AEs) occurred in 94% of patients in the combination arm and 91% of those in the single-agent arm. Additionally, grade 3/4 AEs affected 44% and 31%, grade 3/4 treatment-related AEs (TRAEs) occurred in 13% and 9%, and AEs leading to discontinuation of any therapy affected 3% and 4% between arms, respectively.
Common AEs in both treatment arms included anemia, nausea, asthenia, pyrexia, fatigue, and vomiting. According to Salani, higher rates of AEs were observed with tiragolumab plus atezolizumab, although the combination did not raise any new safety signals in the trial.