Tiragolumab Plus Atezolizumab/Chemo Misses Survival End Points in Metastatic Nonsquamous NSCLC

The addition of tiragolumab (MTIG7192A) to atezolizumab (Tecentriq) and chemotherapy failed to improve progression-free survival (PFS) and overall survival (OS) compared with pembrolizumab (Keytruda) plus chemotherapy in the first-line treatment of patients with locally advanced, unresectable or metastatic nonsquamous non–small cell lung cancer (NSCLC), missing the primary end points of the phase 2/3 SKYSCRAPER-06 trial (NCT04619797).¹

In the intention-to-treat population, which consisted of patients treated in phase 2 and 3 cohorts, the tiragolumab-based combination led to reduced efficacy in terms of PFS at the study’s primary analysis (HR, 1.27; 95% CI, 1.02-1.57) and OS at the first interim analysis (HR, 1.33; 95% CI, 1.02-1.73). Notably, OS data were immature at the time of the analysis.

Following the analyses, the study will be unblinded to patients and investigators, and Roche announced that the company intends to stop the study. Findings will be shared with health authorities and presented at an upcoming medical meeting.

“These results are disappointing as it was our hope that this combination might yield improved outcomes for people living with metastatic nonsquamous lung cancer,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, stated in a news release. “We are thankful to all of the patients and healthcare professionals involved in the study, and we will leverage the learnings to inform our scientific understanding of the anti-TIGIT pathway and new avenues in cancer research.”

Tiragolumab is an investigational novel immune checkpoint inhibitor that features an intact Fc region and is designed to selectively bind to TIGIT. The global, randomized, placebo-controlled, double-blinded SKYSCRAPER-06 study evaluated tiragolumab plus atezolizumab and chemotherapy vs pembrolizumab and chemotherapy as first-line treatment for 542 patients with nonsquamous NSCLC.

Patients were required to be at least 18 years of age with histologically or cytologically documented locally advanced, unresectable or metastatic nonsquamous disease that was not eligible for curative surgery and/or definitive chemoradiotherapy. Key inclusion criteria included no prior systemic therapy for metastatic nonsquamous NSCLC; known tumor PD-L1 status; measurable disease per RECIST 1.1 criteria; a life expectancy of at least 12 weeks; and adequate hematologic and end-organ function.²

Patients were excluded if they harbored EGFR or ALK alterations; had a pulmonary lymphoepithelioma–like carcinoma subtype of NSCLC; had symptomatic, untreated, or actively progressing central nervous system metastases; had active or a history of autoimmune disease or immune deficiency; or had a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced or idiopathic pneumonitis, or evidence of active pneumonitis.

Investigators randomly assigned patients in a 1:1 fashion to receive 600 mg of tiragolumab plus 1200 mg of atezolizumab and chemotherapy once every 3 weeks; or placebo plus 200 mg of pembrolizumab and chemotherapy once every 3 weeks. The chemotherapy regimen in each arm consisted of 500 mg/m² of pemetrexed plus 75 mg/m² of cisplatin or carboplatin at area under the curve 5 once every 3 weeks.

Investigator-assessed PFS and OS served as the trial’s primary end points during phases 2 and 3. Overall response rate (ORR) was a primary end point during phase 2. Key secondary end points included OS (phase 2); independent review facility–assessed PFS (phase 3); investigator-assessed PFS based on PD-L1 status (phase 3); OS based on PD-L1 status; investigator-assessed ORR (phase 3); duration of response (phases 2 and 3); and safety.

Regarding safety, findings for the combination of tiragolumab plus atezolizumab and chemotherapy were consistent with previously reported data. No new or unexpected safety findings were reported.¹

References

1. Roche provides update on phase II/III SKYSCRAPER-06 study in metastatic non-squamous non-small cell lung cancer. News release. Roche. July 4, 2024. Accessed July 8, 2024. https://www.roche.com/media/releases/med-cor-2024-07-04
2. A study of tiragolumab in combination with atezolizumab plus pemetrexed and carboplatin/​cisplatin versus pembrolizumab plus pemetrexed and carboplatin/​cisplatin in participants with previously untreated advanced non-squamous non-small cell lung cancer (SKYSCRAPER-06). ClinicalTrials.gov. Updated June 21, 2024. Accessed July 8, 2024. https://www.clinicaltrials.gov/study/NCT04619797