Abstract 2090
Background
AL 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.
Methods
Patients 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 12 mg for 14 days on a 21 day 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.
Results
In 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.
Conclusions
AL3818 has demonstrated positive combined synergic efficacy with standard platinum-based plus/or paclitaxel chemotherapy in both endometrial and ovarian cancer patients.
Clinical trial identification
NCT02584478.
Editorial acknowledgement
Legal entity responsible for the study
Advenchen Laboratories, LLC.
Funding
Advenchen Laboratories.
Disclosure
Z. 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.
Resources from the same session
2104 - Clinical implications of regorafenib-induced hypothyroidism in metastatic colorectal cancer refractory to standard therapies: A prospective evaluation
Presenter: Jwa Hoon Kim
Session: Poster Display session 2
Resources:
Abstract
2143 - Clinical impact of BRAF V600E mutations in patients (pts) with resectable solitary colorectal liver metastases (CRLM)
Presenter: Shin Kobayashi
Session: Poster Display session 2
Resources:
Abstract
3136 - Trifluridine/tipiracil in metastatic colorectal cancer: an updated multicentre real-world analysis on efficacy, safety and predictive factors.
Presenter: Chara Stavraka
Session: Poster Display session 2
Resources:
Abstract
4234 - Correlation between p53 expression and clinical outcome in RAS/BRAF wild type metastatic colorectal cancer patients receiving later-line irinotecan-cetuximab
Presenter: Eleonora Lai
Session: Poster Display session 2
Resources:
Abstract
4287 - Safety and effectiveness of aflibercept + FOLFIRI for the treatment of patients with metastatic colorectal cancer (mCRC): OZONE secondary analyses
Presenter: Ian Chau
Session: Poster Display session 2
Resources:
Abstract
1820 - A Phase Ib study of the safety and efficacy of atezolizumab (atezo) + bevacizumab (bev) + cobimetinib (cobi) in patients (pts) with metastatic colorectal cancer (mCRC)
Presenter: Johanna Bendell
Session: Poster Display session 2
Resources:
Abstract
5644 - Development and validation of a metastasis-associated immune prognostic model for concurrent metastatic colorectal cancer
Presenter: Zhiwen Luo
Session: Poster Display session 2
Resources:
Abstract
5697 - Prognostic role of blood cell count-based immuno-inflammatory parameters in the Valentino trial
Presenter: Giovanni Fuca
Session: Poster Display session 2
Resources:
Abstract
4704 - Evaluation of safety, immunogenicity and preliminary efficacy of PolyPEPI1018 vaccine in subjects with metastatic colorectal cancer (mCRC) with a predictive biomarker
Presenter: Joleen Hubbard
Session: Poster Display session 2
Resources:
Abstract
3266 - Morphology of tumor-associated macrophages dictates the prognosis of patients with colorectal liver metastases.
Presenter: Matteo Donadon
Session: Poster Display session 2
Resources:
Abstract