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SEOUL, South Korea -- 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 (ORR) in the phase II SKYSCRAPER-04 trial.

The ORR with the combination was 19.0%, which surpassed the historical benchmark of 14.6% (P=0.0787), but failed to beat an ORR of ≥21% (one-sample z-test P≤0.0245) that was required to demonstrate significant improvement, reported Ritu Salani, MD, of the University of California Los Angeles at the annual meeting of the International Gynecologic Cancer Society.

However, in both treatment groups, ORRs were higher in patients with high PD-L1 expression (defined as tumor proportion score ≥10) than PD-L1 low (tumor proportion score ≥5 and <10). A post hoc exploratory analysis also showed that ORR was slightly higher in patients with independent review committee (IRC)-determined measurable disease.

Moreover, Salani noted that adding tiragolumab to atezolizumab was well tolerated, resulting in treatment discontinuation in just 3% of patients.

Thus, "these data add to accumulating evidence supporting dual targeting of TIGIT and PD-L1 in cervical cancer," Salani said.

In addition to the overall response rates described above with the combination, Salani and colleagues found the ORR was:

• 15.6.% with atezolizumab monotherapy
• For patients with PD-L1 high expression, 25.0% with the combination and 20.7% with atezolizumab alone
• For patients with PD-L1 low expression, 10.0% and 6.3% in the two groups, respectively
• For patients with measurable disease by IRC, 21.6% and 15.6%, respectively

Progression-free survival (PFS) averaged 2.8 months with the combination and 1.9 months with atezolizumab, with 12-month rates of 18% and 13%. Overall survival was 11.1 months and 10.6 months in the two arms, respectively.

In explaining the background of , Salani noted that cervical cancer cells increase PD-L1 expression, "which makes inhibition of PD-1 or PD-L1 a very attractive strategy for recurrent cervical cancer."

She pointed out that PD-1 inhibition as monotherapy has demonstrated ORRs of 14-20% in PD-L1-positive populations and 15%-16% in unselected populations. More recently, the demonstrated an overall survival benefit with cemiplimab (Libtayo) compared with single-agent chemotherapy among patients with recurrent cervical cancer after first-line platinum-containing chemotherapy.

"This supports the concept of dual immune blockade with tiragolumab and atezolizumab, which is hypothesized to restore and augment immune response by overcoming immune suppression," Salani said, adding that this is supported by the phase II in non-small cell lung cancer [NSCLC], which demonstrated that tiragolumab plus atezolizumab could be a suitable first-line treatment option for patients with advanced or metastatic NSCLC and high PD-L1 expression defined as a tumour proportion score ≥50%.

SKYSCRAPER included 171 patients with recurrent or persistent cervical cancer not amenable to curative treatment. These patients were PD-L1 positive, had measurable disease, and had one or two previous lines of chemotherapy and at least one line of platinum-based chemotherapy.

Patients in the combination arm had a median age of 49.5, while those in the atezolizumab arm had a median age of 52. About 80% of patients in each arm had received prior chemoradiotherapy, while 22% of patients in the combination arm had received two prior lines of systemic therapy compared with 38% of patients in the atezolizumab arm.

Most patients had received prior paclitaxel, and approximately one-third of patients had received prior bevacizumab (Avastin).

Patients were randomized to either tiragolumab 600 mg intravenously every 3 weeks plus 1,200 mg of atezolizumab every 3 weeks (126 patients) or atezolizumab 1,200 mg every 3 weeks (45 patients).

At the time of data cutoff and with a median follow-up of 10.4 months, 17 patients were still undergoing treatment in the combination arm, and six in the atezolizumab arm. Tiragolumab was added to 15 patients in the atezolizumab arm, three of whom were still undergoing treatment at data cutoff.

Regarding safety, 94% of patients in the tiragolumab-atezolizumab arm had an adverse event (AE) of any grade, compared with 91% of patients in the monotherapy arm. Grade 3/4 events occurred in 44% of patients in the combination arm and 31% in the monotherapy arm, while grade 5 events occurred in 2% of patients in each arm.

Serious AEs occurred in 29% of patients in the combination arm, and 27% in the atezolizumab monotherapy arm, while AEs leading to treatment withdrawal occurred in 3% and 4% of patients, respectively.

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