KEY TAKEAWAYS
- The phase 3 trial aimed to investigate the efficacy and safety of combining TIS with sitra vs doc in patients with NSCLC.
- The primary endpoints were to determine OS & PFS and the secondary endpoints were ORR and TEAEs.
- Researchers noted that TIS plus sitra had similar efficacy to doc but with more AEs.
For patients with advanced Non -Small Cell Lung Cancer (NSCLC) who have previously undergone chemotherapy and/or anti-PD-1/PD-L1 therapy, there are limited treatment options. Tislelizumab (TIS) is an anti-PD-1 antibody, while Sitravatinib (sitra) is a receptor tyrosine kinase inhibitor that can transform the immunosuppressive tumor microenvironment into an immunostimulatory one. The combination of sitra with TIS could potentially address initial resistance to checkpoint inhibitors.
Yi Long Wu and the team aimed to assess the comparative effectiveness and safety profile of TIS plus sitra versus Docetaxel (doc) in this patient population.
They performed an inclusive analysis involving adults (≥18 years) with unresectable locally advanced or metastatic histologically or cytologically confirmed NSCLC (ECOG PS ≤1), who had previously received ≤2 lines of systemic chemotherapy and anti-PD-(L)1 antibodies. Patients were randomized 1:1 to receive either TIS 200 mg intravenously every 3 weeks (Q3W) in combination with sitra 100 mg orally daily (TIS+sitra) or doc 75 mg/m² intravenously Q3W.
Treatment continued until disease progression, intolerable toxicity, death, or withdrawal of consent. The co-primary endpoints were overall survival (OS) and progression-free survival (PFS) assessed by an independent-review committee (IRC). Secondary endpoints included objective response rate (ORR) by RECIST v1.1 and treatment-emergent adverse events (TEAEs).
About 187 patients (December 20, 2023) were randomized to receive TIS+sitra and 190 patients to doc. The median age was 63.0 years for both groups, with a median follow-up of (8.0/7.6 months). Most patients in both groups were male (81.8%/79.5%), Asian (93.6%/93.2%), had an ECOG PS of 1 (74.9%/75.8%), had received one line of prior chemotherapy (75.9%/73.7%), and had metastatic disease (77.0%/74.2%).
The median overall survival (OS) was 11.5 months (95% CI: 9.4-14.6) for TIS+sitra and 11.4 months (95% CI: 9.9-15.0) for doc, with a hazard ratio (HR) of 1.02 (95% CI: 0.75-1.39). Median IRC-assessed PFS was 4.4 months (95% CI: 4.0-5.7) for TIS+sitra and 2.9 months (95% CI: 2.6-4.2) for doc, with a HR of 0.82 (95% CI: 0.62-1.07). IRC-assessed ORR was 12.3% (95% CI: 8.0%-17.9%) for TIS+sitra and 12.6% (95% CI: 8.3%-18.2%) for doc.
The incidence of TEAEs was higher with TIS+sitra compared to doc. Grade ≥3 TEAEs occurring in ≥5% of patients were hypertension (13.4% for TIS+sitra and 1.1% for doc), pneumonia (9.1% for TIS+sitra and 8.5% for doc), palmar-plantar erythrodysesthesia syndrome (6.5% for TIS+sitra and 0% for doc), hypokalemia (5.4% for TIS+sitra and 2.3% for doc), white blood cell count decreased (0% for TIS+sitra and 29.4% for doc), neutrophil count decreased (0.5% for TIS+sitra and 28.8% for doc), neutropenia (0.5% for TIS+sitra and 7.3% for doc), and febrile neutropenia (0% for TIS+sitra and 5.6% for doc). The trial was terminated due to safety risks and an unfavorable benefit-risk analysis.
The study concluded that in patients with previously treated advanced/metastatic NSCLC, TIS+sitra demonstrated comparable efficacy to Docetaxel but was associated with a higher incidence of TEAEs.
The trial is sponsored by BeiGene.
Source: https://cattendee.abstractsonline.com/meeting/20598/presentation/2569
Clinical Trial: https://clinicaltrials.gov/study/NCT04921358
Wu Y.L, Zhou Q, Gao B, et al. (2024). “SAFFRON-301: Tislelizumab Plus Sitravatinib in Advanced/Metastatic NSCLC Progressing on/after Chemotherapy and Anti-PD-(L)1.” Presented at IASLC-WCLC 2024, September 8, 2024; Singapore.
