SKB264, a next-generation antibody-drug conjugate (ADC), marks a significant leap forward in cancer treatment. It combines an anti-TROP2 antibody with a potent topoisomerase I inhibitor through precise site-specific conjugation and a highly stable linker. Phase II trials are on the horizon in both the US and China, targeting patients with locally advanced or metastatic solid tumors resistant to current therapies. Building on promising results from preclinical and Phase I studies, SKB264 has demonstrated notable efficacy across various solid tumors, boasting an enhanced safety profile compared to other TROP2 ADCs.

In December 2022, Merck and Sichuan Kelun Pharmaceutical entered into an exclusive license and collaboration agreement to develop investigational preclinical antibody-drug conjugates (ADC) for the treatment of cancer. These collaborative efforts hold immense potential to redefine cancer treatment paradigms and offer new hope to patients worldwide.

At ASCO, data disclosed as of January 2024 indicated that Cohort 1A enrolled 40 patients and Cohort 1B enrolled 63, showcasing encouraging outcomes. In Cohort 1A, after a median follow-up of 14.0 months, the ORR stood at 48.6%, DCR at 94.6%, and median PFS at 15.4 months with a 6-month PFS rate of 69.2%. In Cohort 1B, with a median follow-up of 6.9 months, the ORR reached 77.6%, DCR was 100%, and median PFS was not yet reached, boasting a 6-month PFS rate of 84.6%. Additional subgroup analysis of Cohort 1B was also performed. In Cohorts 1A and 1B, the most common Grade ≥ 3 TRAEs were neutrophil count decreased, WBC decreased, anemia, rash, and drug eruption. Treatment-related adverse events leading to discontinuation of OptiTROP-Lung01 occurred in 1 patient of Cohort 1B due to drug hypersensitivity, and there were no treatment-related deaths. SKB264 in combination with KL-A167 demonstrated promising efficacy results in the treatment of naive advanced NSCLC with a manageable safety profile.

KOL insights

“Anti-TROP-2 ADCs represent an innovative upcoming weapon against both non-small cell lung cancer and small cell lung cancer subtypes, pending the results of several ongoing trials. The proper combination and placement of this agent throughout the lung cancer treatment pathway, the identification of potentially predictive biomarkers of benefit, as well as the optimal management and impact of peculiar toxicity.” –Expert Opinion.

“In the OptiTROP-Lung01 trial, the combination of sacituzumab tirumotecan and KL-A167 as first-line treatment for non-small cell lung cancer, particularly in squamous subtype, shows potential benefits, despite notable toxicities; however, the observed objective response rates (ORRs) offer promising prospects for patients.”–Expert Opinion.

Conclusion

According to the American Cancer Society, out of the total lung cancer cases, approximately 80─85% of lung cancers are NSCLC. SKB264, a third-generation ADC, in combination with KL-A167, has exhibited promising efficacy in Phase II studies for treatment-naive advanced NSCLC patients. The therapy demonstrated high response rates, favorable disease control, and a manageable safety profile. These findings suggest that SKB264 and KL-A167 hold potential as an effective treatment options for patients with advanced NSCLC who have not received prior therapy. Further investigations are warranted to validate these encouraging results and explore the full therapeutic potential of this combination.