Date: 2017-12-16
Type of
information: update on patient enrollment
phase: 1-2
Announcement: update on patient enrollment
Company: Selvita (Poland)
Product: SEL24
Action
mechanism:
- kinase inhibitor/PIM kinase inhibitor/FLT3 kinase inhibitor. SEL24 is a novel, orally-available small molecule, the first potent, dual inhibitor of PIM and FLT3 kinases. PIM and FLT3 protein kinases are over-expressed in multiple hematological cancers and certain solid tumors. SEL24 demonstrates strong cytotoxic effects in AML cell lines, independently of the FLT3 mutation status, in contrast to available target-selective kinase inhibitors. In preclinical studies, SEL24 has shown significant anticancer effects in multiple hematological xenograft models as a single agent, and has demonstrated synergistic effects with marketed standard of care compounds as well as therapies in advanced clinical development, such as cytarabine, without an associated increase in systemic toxicity.
Disease: acute myeloid leukemia
Therapeutic
area: Cancer - Oncology
Country: USA
Trial
details:
- This Phase I/II, open-label, multi-center, dose escalation study will estimate the MTD (or MAD) of SEL24 in patients with acute myeloid leukemiaL. At the end of Part 1 an RD of SEL24 will be selected for further evaluation in Part 2. In Part 2 the safety and anti-leukemic activity of SEL24 will be further assessed in patients who are unfit to receive intensive chemotherapy. (NCT03008187)
Latest
news:
- • On December 16, 2017, Selvita announced that the FDA has lifted the clinical hold, previously announced on October 7, 2017, on Phase I/II clinical trial of SEL24 in patients with relapsed/refractory (R/R) AML. Selvita agreed with the FDA to revise the dose-finding scheme to a standard 3+3 design under an amended protocol based on the recommendations of the FDA.
- • On October 7, 2017 , Selvita announced that the FDA has placed a full clinical hold on the phase I/II clinical trial of SEL24 in patients with relapsed/refractory (R/R) AML, being conducted in the United States. The FDA’s decision follows a Suspected Serious Unexpected Adverse Reaction Report that a fatal stroke in patient in cohort 5 receiving the 150 mg dose of SEL24 has been evaluated by investigator as possibly related to the study treatment. Under this clinical hold, no new patients will be enrolled, and enrolled patients shall not receive SEL24 until the FDA lifts the full clinical hold. As part of this process, Selvita will provide the FDA with the requested additional data and analysis on patients treated with SEL24 as well as a proposed protocol amendment.
- The current open-label, single-agent, dose escalation Phase 1 study of SEL24 was initiated in the first quarter of 2017 in patients with relapsed and refractory acute myeloid leukemia. The study is designed to determine the maximum tolerated dose (MTD) and recommended dose of SEL24 using a continuous, once-daily treatment schedule. The studies were initiated with a 25 mg daily dose which was then escalated following cohort reviews. One AML patient who initiated the treatment with a 150 mg dose of SEL24 as the third patient in this cohort and received four doses of the drug developed a life-threatening grade 4 venous thrombus in the brain with subsequent intracerebral hemorrhage, that required hospitalization. The patient died in hospice four days later due to the cerebral event. The patient’s death was subsequently evaluated as possibly related to SEL24. The safety report and a review of data by the Data Monitoring Committee were submitted to the FDA. The agency has placed a clinical hold on the trial and requested more safety data on the patients who have received SEL24, specific protocol changes and additional guidance to the study staff.
- Selvita plans to comply with the requests formulated by the FDA regarding the amendment of the study protocol, and to provide additional information to the Agency and to the clinical trial centers in a timely manner, in collaboration with the Menarini Group, its global development partner for SEL24. By regulation, the FDA has 30 days from receipt of Selvita’s response to notify the company whether the clinical hold is lifted.
- • On March 17, 2017, Selvita announced that the first patient was dosed with SEL24 in a Phase I/II clinical trial, for acute myeloid leukemia. This Phase I/II study is the first clinical trial initiated by Selvita. The SEL24 clinical program is anticipated to provide important safety, tolerability and biomarker efficacy data for SEL24 to support its clinical potential in AML, other hematological malignancies as well as solid tumors.
- • On April 18, 2016, Selvita announced that the company has submitted an investigational new drug (IND) application to the FDA for SEL24, the first compound to advance in clinical development from the company's internal discovery pipeline. SEL24 has potential application in the treatment of acute myeloid leukemia, non-Hodgkin’s lymphoma, multiple myeloma and other neoplastic disorders.Pending FDA clearance, Selvita intends to initiate a Phase I clinical trial in Q3 2016.
- • On March 31, 2015, Selvita has announced that it is commencing IND-enabling studies for SEL24 project, the company’s first oncology drug candidate. The company has signed a service agreement with Aptuit for the preparation of selected studies for the IND/CTA data package. This includes both the regulatory and GLP (Good Laboratory Practice) toxicology and safety pharmacology testing in rodents and dogs, as well as large-scale GMP (Good Manufacturing Practice) synthesis of the test compound.
Is
general: Yes
