Tiragolumab Combo Does Not Reach Survival End Points in Nonsquamous NSCLC

Developers designed tiragolumab to selectively bind to the immune checkpoint TIGIT, which can restrict how the immune system responds to cancer. According to the press release, previous preclinical research supported the agent’s capability as an immune amplifier when administered in combination with other immunotherapies like atezolizumab.

Combining frontline tiragolumab with atezolizumab (Tecentriq) and chemotherapy did not meet the primary end points of progression-free survival (PFS), or overall survival (OS) compared with pembrolizumab (Keytruda) plus chemotherapy in patients with locally advanced unresectable or metastatic nonsquamous non–small cell lung cancer (NSCLC), according to a press release on first interim analysis findings from the phase 2/3 SKYSCRAPER-06 trial (NCT04619797).¹

Compared with the pembrolizumab combination, tiragolumab-based treatment did not show improvements in PFS (HR, 1.27; 95% CI, 1.02-1.57) or OS (HR, 1.33; 95% CI, 1.02-1.73) across the intent-to-treat population. The OS data were immature at the time of the analysis.

The safety profile of the tiragolumab regimen was comparable with previous reports of each individual agent, and investigators reported no new safety signals. Investigators and patients will become unblinded to the study results, and developers plan to discontinue the trial. Additionally, developers intend to share their findings with regulatory health authorities and present these data at a future medical conference.

“These results are disappointing as it was our hope that this combination might yield improved outcomes for people living with metastatic nonsquamous lung cancer. We are thankful to all the patients and health care 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,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, said in the press release.¹

Developers designed tiragolumab to selectively bind to the immune checkpoint TIGIT, which can restrict how the immune system responds to cancer. According to the press release, previous preclinical research supported the agent’s capability as an immune amplifier when administered in combination with other immunotherapies like atezolizumab. Investigators hypothesized that the TIGIT pathway may be complementary to the PD-L1 or PD-1 pathway, and that dual blockade with tiragolumab/atezolizumab may augment immune responses to disease.

In the international, double-blinded, phase 2/3 SKYSCRAPER-06 trial, patients were assigned to receive tiragolumab at 600 mg intravenously every 3 weeks plus atezolizumab at 1200 mg intravenously every 3 weeks and chemotherapy or pembrolizumab at 200 mg intravenously every 3 weeks in combination with chemotherapy.² Treatment with chemotherapy consisted of pemetrexed at 500 mg/m² every 3 weeks plus cisplatin at 75 mg/m² every 3 weeks, or carboplatin at area under the curve of 5 intravenously every 3 weeks.

The investigator-assessed objective response rate was another primary end point in phase 2 of the trial. The trial’s secondary end points included duration of response, time to confirmed deterioration, serum concentration of tiragolumab, and adverse effects.

Patients 18 years and older with an ECOG performance status of 0 or 1 with histologically or cytologically confirmed locally advanced unresectable or metastatic nonsquamous NSCLC who were not suitable for curative surgery and/or chemoradiation were eligible for enrollment on the trial. Additional requirements for study entry included having no prior systemic treatment, known PD-L1 status, measurable disease per RECIST v1.1 guidelines, a minimum life expectancy of 12 weeks, and adequate hematologic and organ function.

Those with pulmonary lymphoepithelioma-like disease or symptomatic, untreated, or actively progressing central nervous system metastases were unable to enroll on the trial. Patients were also unsuitable for enrollment if they had active or prior autoimmune disease, a severe infection within 4 weeks of beginning study treatment, EGFR or ALK mutations, or targetable ROS1 or BRAF V600E aberrations.

References

1. [Ad hoc announcement pursuant to Art. 53 LR] 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://tinyurl.com/57n5j2tp
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. Accessed July 8, 2024. https://tinyurl.com/3jtewvzb