1033P - Phase Ib/IIa study assessing the safety and efficacy of adding AL3818 (anlotinib) to standard platinum-based chemotherapy in subjects with recurrent or metastatic endometrial, ovarian or cervical carcinoma

Abstract

BackgroundAL 3818 (Anlotinib, Catequentinib) is a novel small molecule tyrosine kinase inhibitor that is administered orally. The primary objective of this study is to evaluate the safety, tolerability, and efficacy of adding AL3818, to standard platinum-based plus/or paclitaxel chemotherapy in patients with recurrent or metastatic endometrial, ovarian or cervical carcinoma in Phase 1b/2a studies. MethodsPatients with a diagnosis of recurrent or metastatic endometrial, ovarian, or cervical carcinomas requiring ≥ 2nd line treatment with standard platinum-based chemotherapy were eligible for enrollment on a 21 days cycle. In the Phase 1b study, after chemotherapy at Day 1, patients were started on Day 8 with daily AL 3818 at an initial dose of 12mg for 14 days on a 21day cycle. A 3+3 dose de-escalation design to 10mg, 8mg, and 6mg to determine the recommended Phase II dose (RP2D) was utilized. In the Phase 2a study, patients were treated with the RP2D in combination with either combination platinum based therapy or single agent paclitaxel based on origin of disease. 1st line endometrial patients are allowed. Maintenance monotherapy with AL3818 was given after chemotherapy stopped. ResultsIn the Phase 1b study: (1) 9 subjects with recurrent or metastatic endometrial, ovarian or cervical carcinomas participated with RP2D determined; (2) common treatment emergent adverse event (TEAE) include abdominal pain), alopecia, anemia, arthralgia, asthenia, back pain, and constipation. Overall, most TEAEs were well tolerated by subjects. In Phase 1b and 2a studies: (1) the objective response rate (ORR) and disease control rate (DCR) were 58% and 79% for 19 evaluable endometrial subjects; (2) ORR and DCR were 50% and 93% for all 14 evaluable ovarian subjects; (3) 48 subjects with recurrent or metastatic endometrial, ovarian, and cervical carcinoma were enrolled in the Phase 2a study. ConclusionsAL3818 has demonstrated positive combined synergic efficacy with standard platinum-based plus/or paclitaxel chemotherapy in both endometrial and ovarian cancer patients. Clinical trial identificationNCT02584478. Legal entity responsible for the studyAdvenchen Laboratories, LLC. FundingAdvenchen Laboratories. DisclosureZ. Li: Full / Part-time employment: Advenchen laboratories. M. Chen: Full / Part-time employment: Advenchen laboratories. J. Chen: Full / Part-time employment: Advenchen laboratories. All other authors have declared no conflicts of interest.