ALM201 is a 23-amino acid peptide derived from FKPB-L, a human endogenous protein with inherent anti-angiogenic activity. ALM201 is active after internalisation via CD44 into the cell, where it binds to tubulin and prevents microtubule formation. Preclinical studies have demonstrated that ALM201 is a potent inhibitor of migration, invasion and new blood vessel formation but has no effects on cell cycle or proliferation. It was very well tolerated in pre-clinical toxicology studies. High grade serous ovarian cancer (HGSOC) is a disease of clinical unmet need, and the role of anti-angiogenics in HGSOC remains a critical area of investigation. The 63-gene AADx biomarker (Gourley et al, ASCO 2014) identifies a sub-group of HGSOC with significant up-regulation of angiogenic genes and a worse outcome from conventional platinum-based chemotherapy. In our trial, we wish to investigate ALM201 in this AADx-selected “Angiogenic” HGSOC population.
This phase I trial employs an accelerated dose-escalation design with single patient cohorts, later moving to a standard 3 + 3 design, and will explore 6 dose levels. Patients will have histologically confirmed advanced solid tumours, in which use of an antiangiogenic is reasonable. The dose expansion cohort will recruit 36 patients and treat them with the recommended phase II dose (RP2D). They will have relapsed advanced HGSOC with a tumour classified as angiogenic by the AADx signature. This companion diagnostic will utilise a pre-enrolment FFPE tumour sample. Patients will receive ALM201 once daily as a subcutaneous injection on days 1-5, 8-12, and 15-19 every 21 days. The primary objectives are to determine the safety, tolerability and RP2D of ALM201. Secondary objectives are to determine the pharmacokinetic profile and preliminary antitumor activity of ALM201 overall and in the biomarker-selected HGSOC population. Exploratory objectives are to assess relevant tumour biomarkers and the pharmacodynamic activity of ALM201. This trial commenced recruitment in July 2015, with 10 patients currently enrolled across the first 6 dose levels.
Clinical trial identification
EudraCT No: 2014-001175-31
Legal entity responsible for the study
V. Coyle: Research funding and site PI: Onyx/Amgen. Travel and accommodation expense covered by sanofi and BM. C. Rogers: consulting/advisory role for AstraZeneca. Y. Drew: Honoraria: AstraZeneca and Clovis Oncology. Consulting and advisory role: AstraZeneca and Clovis Oncology. A. Clamp: Consulting and advisory role: Astra Zeneca. Speakers Bureau: Astra Zeneca and Roche. Research funding: Astra Zeneca, Clovis Oncology, Array Biopharma, AB bioscience and Amgen. A. McCavigan: Employee of Almac Diagnostics. L. Knight: Employee of Almac group. N. McCabe: Employee of Almac group. Research funding from ALmac group. K. Keating: Employed by Almac diagnostics. Research funded by Almac Diagnostics. Hold patent and royalties in ALmac diagnostics. Travel and expenses covered by Almac Diagnostics. R. Dyer: Almac discovery employee, holds patent/royalties through Almac Discovery. Travel/accommodation expenses covered by Almac Discovery. T. Harrison: Employee of Almac Discovery, research funded by Almac Discovery. P. Harkin: Employment: Almac Diagnostics. Research funded by Almac Diagnostics. Patent and royalties held and received by Almac Diagnostics. T. Robson: Research funding: Almac Discovery. Patent/royalties held with Almac Discovery. R. Kennedy: Employee of Almac Diagnostics. Patent and royalties held with Almac Diagnostics. R. Wilson: Honoraria, Advisory roles and travel expenses from Sanofi, Merck Serono, Amgen and Sirtex. All other authors have declared no conflicts of interest.