Kelun-Biotech presented multiple clinical research results of its TROP2-targeting antibody-drug conjugate (ADC) sacituzumab tirumotecan (sac-TMT, formerly SKB264/MK-2870) at the 2024 China Clinical Oncology Congress (CSCO) Annual Meeting. The data highlighted the potential of sac-TMT across various solid tumors, including triple-negative breast cancer (TNBC), non-small cell lung cancer (NSCLC), cervical cancer, endometrial cancer, and ovarian cancer.
Sac-TMT in Triple-Negative Breast Cancer (TNBC)
The Phase III OptiTROP-Breast01 study evaluated sac-TMT in patients with previously treated locally recurrent or metastatic TNBC. The median progression-free survival (PFS) assessed by BICR was 6.7 months (95% CI, 5.5 to 8.0) with sac-TMT compared to 2.5 months (95% CI, 1.7 to 2.7) with chemotherapy (HR 0.32; 95% CI, 0.22 to 0.44; P < 0.00001), representing a 68% reduction in the risk of disease progression or death. In patients with TROP2 H-score > 200, the median PFS was 8.3 months with sac-TMT and 2.3 months with chemotherapy (HR 0.29; 95% CI, 0.19 to 0.46).
The median overall survival (OS) was not reached (95% CI, 11.2 to NE) with sac-TMT and was 9.4 months (95% CI, 8.5 to 11.7) with chemotherapy. The sac-TMT group had a 47% reduction in the risk of death compared to the chemotherapy group (HR 0.53; 95% CI, 0.36 to 0.78; P = 0.00005). Academician Binghe Xu noted that sac-TMT could become the new standard of second-line treatment for advanced TNBC.
Sac-TMT in Non-Small Cell Lung Cancer (NSCLC)
The Phase II OptiTROP-Lung01 study investigated sac-TMT in combination with KL-A167 (an anti-PD-L1 monoclonal antibody) as a first-line treatment for advanced NSCLC without actionable genomic alterations. Patients received sac-TMT 5 mg/kg Q3W + KL-A167 1200 mg Q3W (cohort 1A) or sac-TMT 5 mg/kg Q2W + KL-A167 900 mg Q2W (cohort 1B) in a non-randomized manner.
After a median follow-up of 14.0 months for cohort 1A, the objective response rate (ORR) was 48.6%, the disease control rate (DCR) was 94.6%, and the median PFS was 15.4 months (95% CI: 6.7, NE) with a 6-month PFS rate of 69.2%. For cohort 1B (median follow up of 6.9 months), the ORR was 77.6%, the DCR was 100%, and the median PFS was not reached with a 6-month PFS rate of 84.6%. Professor Wenfeng Fang highlighted the potential of this dual-drug regimen in leading a new direction for first-line NSCLC treatment.
Sac-TMT in Cervical Cancer (CC)
The efficacy and safety of sac-TMT plus pembrolizumab were evaluated in patients with recurrent or metastatic cervical cancer who had progressed on or after platinum-doublet chemotherapy and received no more than two systemic therapies for R/M disease. In 38 patients treated and followed up for at least 17 weeks, the ORR was 57.9% (with 3 complete responses). Responses were observed even in patients pre-treated with anti-PD-1 based therapy. The median PFS was not reached, and the 6-month PFS rate was 65.7%. Professor Jing Wang noted the high TROP2 expression in cervical cancer and the potential for sac-TMT to bring hope to a wider range of cancer patients.
Sac-TMT in Endometrial and Ovarian Cancer (EC/OC)
A Phase 2 study assessed the safety and efficacy of sac-TMT in patients with previously treated advanced endometrial carcinoma (EC) and ovarian cancer (OC). In the endometrial cancer cohort (44 patients), the ORR was 34.1%, the DCR was 75%, and the median PFS was 5.7 months (95% CI: 3.7, 9.4) with a 6-month PFS rate of 47.5%.
In the ovarian cancer cohort (40 patients), the ORR was 40%, the DCR was 75%, the mPFS was 6.0 months (95% CI: 3.9, 7.3), and the mOS was 16.5 months (95% CI: 10.7, NE). In patients with TROP2 IHC H-score > 200, the ORR was 61.5%, while in those with H-score ≤ 200, the ORR was 27.3%. Professor Danbo Wang emphasized the potential of sac-TMT in treating advanced endometrial and ovarian cancers, citing its efficacy and manageable safety profile.
These results suggest that sac-TMT (SKB264) holds promise as a treatment option across a spectrum of solid tumors, particularly those with high TROP2 expression. Kelun-Biotech is dedicated to addressing unmet clinical needs and advancing the development of innovative ADC drugs.
