Sacituzumab Tirumotecan Granted Breakthrough Therapy Designation for NSCLC

For patients with EGFR-mutated non–small cell lung cancer, sacituzumab tirumotecan was given the breakthrough drug designation by the FDA.

Sacituzumab tirumotecan (SKB264) has been granted breakthrough therapy designation by the FDA for patients with previously treated EGFR-mutatedadvanced or metastatic nonsquamous non–small cell lung cancer (NSCLC) whose disease progressed on or after tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy, according to a press release from the developer, Merck.¹

The decision comes following promising data from 2 trials: a phase 2 expansion cohort of the phase 1/2 OptiTROP-Lung01 study (NCT05351788) that is evaluating sacituzumab tirumotecan in patients with EGFR-mutated NSCLC, and a phase 2 study evaluating sacituzumab tirumotecan in patients with EGFR-mutated NSCLC who have been treated with 2 prior lines of therapy.

Scot Ebbinghaus MD, vice president of global clinical development at Merck Research Laboratories said in the press release, “This designation by the FDA highlights the importance of developing novel therapeutic options for patients living with EGFR-mutated nonsquamous non–small cell lung cancer. We believe antibody-drug conjugates [ADCs] are an important modality in the treatment of cancer and are rapidly advancing the clinical development of sacituzumab tirumotecan, with the goal of meaningfully improving upon current standards of care in certain cancers.”¹

Patients in the OptiTROP-Lung01 study were randomly assigned into 1 of 2 cohorts: cohort 1A (n = 40) received 5 mg/kg of sacituzumab tirumotecan once every 3 weeks plus 1200 mg of KL-A167 once every 3 weeks, and cohort 1B (n = 63) received 5 mg/kg of sacituzumab tirumotecan once every 2 weeks plus 900 mg of KL-A167 once every 2 weeks.² Treatment continued until disease progression or unacceptable toxicity was observed.

As of the data cutoff of January 2, 2024, cohort 1A of the OptiTROP-Lung01 study had an objective response rate (ORR) of 48.6%, a disease control rate (DCR) of 94.6%, and a median PFS of 15.4 months (95% CI, 6.7-not evaluable [NE]), and the 6-month PFS was 69.2% (95% CI, 51.2%-81.6%) at a median follow-up of 14.0 months. For cohort 1B at a median follow-up of 6.9 months, the ORR was 77.6% (95% CI, 64.7%-87.5%), DCR was 100%, and median PFS was not reached; the 6-month PFS was 84.6% (95% CI, 71.4%-92.1%).

Regarding safety, the most common grade 3 or higher treatment-related adverse effects (TRAEs) were decreased neutrophil count (30.0% in cohort 1A vs 30.2% in cohort 1B), decreased white blood cell count (5.0% vs 17.5%), anemia (5.0% vs 15.9%), rash (5.0% vs 6.3%), and drug eruption (7.5% vs 0.0%). A total of 1 patient discontinued sacituzumab tirumotecan treatment due to treatment-related AEs, and drug hypersensitivity in cohort 1B. There were no treatment-related deaths.

Per patient characteristics, the median age in cohort 1A and cohort 1B was 63.0 years and 63.0 years, respectively. Also, 97.5% and 85.7% had an ECOG performance score of 1.

Patient inclusion criteria included: histologically and cytologically confirmed NSCLC, fresh or archival tumor tissue for biomarker testing, at least 1 measurable lesion per RECIST v1.1 (patients with only skin or bone lesions cannot be enrolled), an ECOG performance score of 0 to 1 with an expected survival of 12 weeks or greater, and adequate organ and bone marrow function, among others.³

Patients were excluded if they had any of the following: history of other malignancies; the presence of small cell lung carcinoma components in histological pathology; the presence of metastases to the brainstem, meninges, and spinal cord, or spinal cord compression; if imaging shows that tumor surrounds important blood vessels; or if they have known active tuberculosis, among others.

Recently. sacituzumab tirumotecan received marketing authorization from the National Medical Products Administration in China.⁴ This authorization is for the treatment of patients with unresectable locally advanced or metastatic triple-negative breast cancer.

References

1. FDA grants breakthrough designation to sacituzumab tirumotecan (sac-TMT) for the treatment of certain patients with previously treated advanced or metastatic nonsquamous non-small cell lung cancer with EGFR mutations. News release. Merck. December 3, 2024. Accessed December 4, 2024. https://tinyurl.com/m5fjvcww
2. Fang W, Wang O, Cheng Y, et al. Sacitizumab tirumotecan (SKB264/MK-2870) in combination with KL-A167 (anti-PD-L1) as first-line treatment for patients with advanced NSCLC from the phase II OptiTROP-Lung01 study. J Clin Oncol. 2024;42(suppl 16):8502. doi:10.1200/JCO.2024.42.16_suppl.8502
3. SKB264 combination therapy in patients with advanced or metastatic non-small cell lung cancer. News release. ClinicalTrials.gov. Updated December 14, 2023. Accessed December 4, 2024. https://tinyurl.com/3t4cwbrp
4. Kelun-Biotech’s TROP2 ADC sacituzumab tirumotecan (sac-TMT, 佳泰莱) approved for marketing by NMPA Of China for 2L+ advanced or metastatic TNBC. News release. Sichuan Kelun-Biotech Biopharmaceutical. November 27, 2024. Accessed December 4, 2024. https://tinyurl.com/2rzk3r2n