716MO - Efficacy and safety of sacituzumab tirumotecan (sac-TMT) plus pembrolizumab in patients with recurrent or metastatic cervical cancer

Background

Anti-PD-1 antibody is the standard therapy for recurrent or metastatic (R/M) cervical cancer (CC) patients (pts) after platinum-based chemotherapy. It was shown that ADC combined with PD-1/L1 antibody has a potential additive effect. Sac-TMT (also known as MK-2870/ SKB264) is a TROP2 ADC developed with novel linker to conjugate a belotecan-derivative topoisomerase I inhibitor. Here, we report the efficacy and safety results from the CC cohort in an ongoing Phase 2 basket study (SKB264-Ⅱ-06, NCT05642780).

Methods

Pts with R/M CC who had progressed on or after platinum-doublet chemotherapy and received no more than 2 systemic therapies for R/M disease were enrolled. Sac-TMT 3 or 5 mg/kg Q2W+ pembrolizumab 400 mg Q6W were assessed in safety run-in period and the doses deemed well tolerated were being explored in expansion period. Tumor assessments per RECIST 1.1 were performed once every 8 weeks for the first 12 mo, and every 12 weeks thereafter.

Results

As of March 25, 2024, 38 pts were treated and followed up for at least 17 weeks or 2 tumor assessments (3 received sac-TMT 3 mg/kg, 35 received sac-TMT 5 mg/kg). The median follow-up was 6.2 mo. The median age was 52 years. 76.3% had squamous histology. 47.4% had received two prior lines of therapy, 52.6% had received bevacizumab, and 42.1% had received anti-PD-1 based therapy. The ORR was 57.9% (22/38, 3 unconfirmed), with 3 complete responses. Median DoR was not reached and 6-mo DoR rate was 82.1%. Responses were also observed in pts were pre-treated with anti-PD-1 based therapy (ORR 68.8%, 11/16). Median PFS was not reached and 6-mo PFS rate was 65.7%. Grade ≥ 3 treatment-related AEs (TRAEs) occurred in 47.4% of pts. The most common Grade ≥ 3 TRAEs were neutrophil count decreased (23.7%), anemia (21.1%) and WBC decreased (15.8%). TRAEs led to dose reduction of sac-TMT in 44.7% of pts. TRAE led to discontinuation of sac-TMT in 1 pt (2.6%). No TRAEs led to discontinuation of both drugs.

Conclusions

Sac-TMT plus pembrolizumab demonstrated promising and durable antitumor activity with manageable safety profile. No new safety signal was observed. Considering the activity of this combination among pts who were pre-treated with anti-PD-1 based therapy, further investigation is warranted.

Clinical trial identification

NCT05642780; first posted December 8, 2022.

Editorial acknowledgement

Legal entity responsible for the study

Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd., Chengdu, China.

Funding

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

J.C.H. Goh: Financial Interests, Personal, Stocks or ownership: ICON Cancer Care; Financial Interests, Personal, Speaker, Consultant, Advisor: Ipsen, MSD Oncology; Financial Interests, Personal, Advisory Role: GSK; Financial Interests, Personal, Invited Speaker: Ipsen, MSD Oncology, AstraZeneca/MedImmune, Bayer; Financial Interests, Personal, Non financial benefits: Bayer. B. Akala: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.. E. Chartash: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.. Y. Zhou, X. Jin, J. Ge: Financial Interests, Personal, Full or part-time Employment: Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. All other authors have declared no conflicts of interest.