Sacituzumab govitecan clinical trial

Sacituzumab govitecan showed encouraging anti-tumor activity in a first-in-human clinical trial in patients with metastatic solid tumors. In the dose-escalation portion of Phase I, gosatuzumab was administered at doses of 8, 10, 12, or 18 mg/kg on days 1 and 8 of the 3-week treatment cycle for up to 8 cycles, or until disease progression or unacceptable toxicity. Among 25 patients, 2 patients achieved partial response and 16 patients had stable disease. Overall, three patients had a ≥30% reduction in target lesions. The maximum tolerated dose is 12mg/kg. In the first cycle, dose levels of 8 and 10 mg/kg were associated with acceptable tolerability, allowing repeated dosing. In the phase II dose expansion portion of the IMMU-132-01 trial, 178 patients with advanced solid tumors received 8 or 10 mg/kg of gosatuzumab, with the 10 mg/kg dose having numerically better objective response rates (ORR) and clinical benefit rates (CBR) compared with the 8 mg/kg dose.

In the basket-design, open-label, single-armIMMU-132-01 trial, cancergosatuzumab versus 108 patientsMetastatic triple-negative breast cancer (mTNBC)Heavily pretreated patientsORR of 33.3%, with objective responses including three complete responses (CR) and 33 PRs. The CBR (percentage of patients with CR, PR, or stable disease ≥ 6 months) was 45.4%, and the median duration of response was 7.7 months. The median progression-free survival (PFS) was 5.5 months, and the median overall survival (OS) was 13.0 months. The median duration of follow-up was 9.7 months.

In IMMU-132-01, the ORR for gosatuzumab was consistent regardless of estrogen receptor (ER) status. In a pooled analysis of 162 patients with HER2-negative cancers (108 TNBC and 54 ER-positive), the ORR was 33%, the median DOR was 8.3 months, PFS was 5.6 months, and OS was 13.0 months. In the ER-positive subgroup, the ORR was 31% and the median DOR was 7.4 months. Among 69 patients who had received five treatments since IMMU-132-01 diagnosis, the ORR was 30%, the CBR was 46%, and the median DOR was 8.9 months. Responses occurred early in the course of treatment, with a median time to onset of 1.9 months. The median PFS and OS were 6.0 months and 16.6 months, respectively.

In theIMMU-132-01 trial,gosatuzumabDemonstrated clinical activity in patients with metastatic urothelial carcinoma. The patient had received at least one previous treatment. ORR was 31% in the entire cohort, 27% in those with visceral involvement, and 23% in those previously treated with checkpoint inhibitors. CBR is 47%. The median DOR is 12.9 months. Median PFS and OS were 7.3 months and 16.3 months, respectively. In an interim analysis of the open-label, multinational, phase II TROPHY-U-01 trial, gosatuzumab was associated with an ORR of 29% in patients with platinum- or immunotherapy-resistant metastatic urothelial cancer. During the transition period in cohort 1, 35 patients had ORRs that exceeded the prespecified Simon phase 2 rule. Objective responses included two confirmed CRs, six confirmed PRs, and two unconfirmed PRs. Among patients with liver involvement, the ORR was 25%, and 74% had target lesion reduction.