A phase i trial of volasertib administered on days 1 and 8 every 21 days is currently ongoing nct00969553. Phase ii clinical data for volasertib are more promising than for ganetespib, and boehringer ingelheim is seeking to demonstrate volasertib s efficacy in a largescale phase iii clinical trial. A phase i ii study evaluated the safety, efficacy and pks of volasertib plus ldac and volasertib monotherapy in patients with aml ineligible for. But volasertib has insufficient antitumor activity as a monotherapy in the phase ii trial of locally advanced or metastatic urothelial cancer. Volasertib is currently undergoing investigation in phase i and ii trials and has yet to be licensed by the fda. This nintedanib dose is currently being evaluated in phase iii trials and was selected based on the findings of phase i ii studies 15, 17, 18. Boehringer ingelheim presents new phase ii data for. Safer at home for vulnerable populations remove ban on social gatherings. In a phase i74 study of volasertib proceeding the phase ii trial74 in. Boehringer ingelheim has a rich pipeline showing a number of new molecular entities and a high share of products in late phase development.
Ibrutinib rituximab phase ii ibrutinib showed promising monotherapy activity in patients with cll with an orr of 71% and additional 20% patients achieving pr with lymphocytosis. Here, we report the phase i results, including maximum tolerated dose mtd, safety. Results of phase iii study of volasertib for the treatment of. Aug 10, 2016 patients receive volasertib iv over 1 hour on day 1 and vincristine sulfate liposome iv over 1 hour on days 1, 8, 15, and 22. Subsequent patients were randomized to volasertib n 37, volasertib with pemetrexed n 47, or pemetrexed n 47 administered on day 1 every 21 days. Jul 16, 2014 the phase i, doseescalation part of the trial, conducted in patients with relapsedrefractory aml, identified the recommended dose of volasertib as 450 mg every second week as a single agent and. A combined phase i ii trial investigated volasertib in patient populations with aml who were ineligible for intensive treatment. Volasertib has been used in both phase i and phase ii clinical studies, including for pediatric aml nct01971476, but has not been investigated for hepatoblastoma. To collect additional data on safety, efficacy and pharmacokinetics and to confirm the recommended phase ii dose rp2d, of volasertib in combination with decitabine in previously untreated patients with aml. Oncotarget volasertib preclinical activity in highrisk. The phase ii results, in patients with previously untreated aml, have been previously reported dohner et al, 2014. Discovery and development of the pololike kinase inhibitor. Jul 17, 2015 in a phase i74 study of volasertib proceeding the phase ii trial74 in combination with lowdose cytarabine ldac in relapsedrefractory aml, volasertib was given in a dose escalation manner on day 1 and day 15 every 4 weeks q4w alone or in combination with subcutaneous ldac 20 mg bid on days 110 q4w in a dose deescalation fashion. This phase ii trial evaluated volasertib or singleagent chemotherapy in patients with platinumresistant or refractory ovarian cancer who experienced failure after treatment with two or three therapy lines.
Pdf pololike kinase 1 plk1, a member of the pololike kinase family of serinethreonine kinases. Plk1 is the best characterized kinase of the plk family. Phase i ii study of volasertib bi 6727, an intravenous pololike kinase plk inhibitor, in patients with acute myeloid leukemia aml. In a phase ii trial including 87 patients with aml, cotreatment with volasertib and cytarabine significantly prolongs median overall survival and median eventfree survival but increases. Nine phase 1 trials, 4 phase 2 trials, and 1 phase 3 trial evaluating volasertib in adult patients with cancer including acute myeloid leukemia, nonsmall cell lung cancer, ovarian carcinoma, urothelial carcinoma, and other types of solid tumors were either completed or still ongoing. Volasertib inhibits cancer growth by disrupting cell division and inducing cell death. Phase ii clinical data for volasertib are more promising than for ganetespib, and boehringer ingelheim is seeking to demonstrate volasertibs efficacy in a largescale phase iii clinical trial.
Volasertib and vincristine sulfate liposome in treating. Aug 28, 2014 in this randomized, phase 2 study, we compared efficacy and safety of ldac with and without volasertib, a highly potent and selective inhibitor of plk, in previously untreated patients with aml considered unsuitable for intensive therapy. Although patients were heavily pretreated, volasertib demonstrated antitumor activities with seven 14% patients achieving a partial response and 26% achieving stable disease as the best response 34. This dose was defined as the recommended dose for phase 2 trials from a dose. Two phase ii trials of volasertib are ongoing in advanced ovarian cancer and advanced nsclc table 2. Aml is particularly prevalent in the elderly and is the most common form of leukaemia in adults, with the lowest survival rate. Phase i ii study of bi 6727 volasertib, an intravenous pololike kinase1 plk1 inhibitor, in patients with acute myeloid leukemia aml. This randomized, phase ii trial n 143 investigated volasertib monotherapy or in. In a phase i 74 study of volasertib proceeding the phase ii trial 74 in combination with lowdose cytarabine ldac in relapsedrefractory aml, volasertib was given in a dose escalation manner on day 1 and day 15 every 4 weeks q4w alone or in combination with subcutaneous ldac 20 mg bid on days 110 q4w in a dose deescalation fashion.
The phase ii poloaml2 trial will recruit 660 previouslyuntreated aml patients aged 65 and older who are ineligible for highintensity therapy who will be treated with either ldac alone or ldac plus volasertib. Volasertib binds to plk1, plk2 and plk3, but has a modest selectivity for plk1 cellfree enzyme ic 50 values of 0. Although patients were heavily pretreated, volasertib demonstrated antitumor activities with seven 14% patients achieving a partial response. Mar 02, 20 boehringer ingelheim begins phase iii study of volasertib in patients with aml. This study will determine the maximum tolerated dose mtd of this combination by treating cohorts of patients at a certain dose combination. Volasertib is a potent and selective cellcycle kinase inhibitor that induces mitotic arrest and apoptosis by targeting pololike kinase. Reta ii instore purchases allowed bars at phase 2 could last 2 4 weeks or longer. Acp196 btkinhibitor phase i acp196 is a novel oral btkinhibitor in clinical development. A phase i study of volasertib combined with afatinib, in. Longerterm to move to phase iii, were looking for no evidence of rebound for a sustained period of time. Boehringer ingelheim initiaties pivotal trial on volasertib. Boehringer ingelheim initiaties pivotal trial on volasertib for acute myeloid leukaemia boehringer ingelheim invests in rare diseases with high unmet medical need.
Strategic and statistical considerations on the qt. There was no apparent correlation between the white blood cell. Development of cellcycle checkpoint therapy for solid tumors. Apr 22, 2014 volasertib had antitumour activity in this cancer patient population comparable to that observed in other phase iii trials in western populations schoffski et al, 2012. By adding volasertib to ldac, the overall response was more than doubled, with 31% vs % for ldac alone. In a randomized, phase ii trial in patients with previously untreated aml ineligible for intensive therapy, volasertib combined with ldac improved remission rate 31% vs %. A phase iii trial nct01721876 was conducted to confirm the phase ii results. Importantly, responses are seen across all cytogenetic risk groups and in heavily pretreated fludarabinerefractory patients. Strategic and statistical considerations on the qt assessment of volasertib. Phase 3volasertib for acute myeloid leukaemia in patients. Boehringer takes leukaemia drug volasertib into phase iii. Nov 05, 2019 volasertib binds to plk1, plk2 and plk3, but has a modest selectivity for plk1 cellfree enzyme ic 50 values of 0. However, volasertib would compete with synta pharmaceuticals phase iii ganetespib, which is also targeting the same population.
Patients receive volasertib iv over 1 hour on day 1 and vincristine sulfate liposome iv over 1 hour on days 1, 8, 15, and 22. Patients with advanced nonresectable andor metastatic disease following failure of conventional treatment received intravenous volasertib 150300 mg on day 1. A combined phase iii trial investigated volasertib in patient populations with aml who were ineligible for intensive treatment. Randomized, phase 2 trial of lowdose cytarabine with or. A randomized, openlabel phase ii trial of volasertib as. A phase i study of two dosing schedules of volasertib bi. Volasertib is a potent and selective cell cycle kinase inhibitor that induces mitotic arrest and apoptosis by targeting pololike kinase. This is a phase i study of the combination of volasertib and romidepsin in patients with relapsedrefractory peripheral t cell lymphoma ptcl or stage iibiv cutaneous t cell lymphoma ctcl. Triple angiokinase inhibitor, simultaneously blocks vegfr, fgfr, pdgfr. Boehringer ingelheims investigational volasertib receives. Boehringer ingelheim begins phase iii study of volasertib. Volasertib, boehringer ingelheims investigational oncology.
A phase ii trial of volasertib was undertaken in 50 patients with metastatic. A runin phase n 12 was used to determine whether volasertib could be combined in full dose with pemetrexed 500 mgm 2. Volasertib suppresses the growth of human hepatocellular. Acp196 is provided at no charge for patients on this study.
Acute myeloid leukemia aml cellcycle kinase inhibition. Volasertib versus chemotherapy in platinumresistant or. Ph1 volasertib plus romidepsin in rr ptcl and ctcl full. Mar 06, 20 with the enrollment of the first patient, boehringer ingelheim is pleased to announce on international rare disease day, the initiation of a phase iii study poloaml2 investigating volasertib, a selective and potent pololike kinase plk inhibitor, in combination with chemotherapy, in patients with acute myeloid leukaemia aml ineligible for intensive therapy.
Patients with advanced nonresectable andor metastatic disease following failure of conventional treatment received intravenous volasertib 150300 mg on day 1 every. Volasertib is in phase iii clinical development for acute myeloid leukaemia and nintedanib is in phase iii clinical development for idiopathic pulmonary fibrosis. Plk1 inhibitors in cancer therapy molecular cancer therapeutics. Volasertib is administered as a 350mg one hour intravenous iv infusion on days 1 and 15 of a 28 day cycle in combination. A phase ii trial of volasertib was undertaken in 50 patients with metastatic urothelial cancer following platinum failure.
Phase iiia trial of volasertib combined with decitabine. Results of the dose finding for bi 6727 in combination with lowdose cytarabine. Pdf efficacy and mechanism of action of volasertib, a potent and. The response rate cr and cri in the ldac plus volasertib arm was 31% of 42 patients compared to.
Volasertib acts as a brd4 inhibitor in biochemical assays. Nintedanib treatment was started 7 days before treatment with volasertib to induce nintedanib steadystate levels at the time of first volasertib administration. Clinical development of volasertib in phase ii monotherapy and combination trials is ongoing. Pdf strategic and statistical considerations on the qt. This trial is open for firstline treatment of patients with cll. Prnewswire boehringer ingelheim pharmaceuticals, inc. Phase iiia trial of volasertib combined with decitabine in.
Original article volasertib suppresses tumor growth and potentiates. May 02, 2016 this is a phase i study of the combination of volasertib and romidepsin in patients with relapsedrefractory peripheral t cell lymphoma ptcl or stage iibiv cutaneous t cell lymphoma ctcl. Phase i doseaescalation study of volasertib in pediatric patients. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression, development of an intercurrent illness that prevents further administration of treatment, unacceptable toxicity, patient decides to withdraw or treating investigator determines. Boehringer ingelheim begins phase iii study of volasertib in patients with aml.
Pdf pololike kinase 1 plk1, a member of the pololike kinase family of serine threonine kinases. Development of cellcycle checkpoint therapy for solid. Volasertib phase ib ii trial begins august 2019 licensing agreement with bi these timings are estimations based on discussions with kols and analogies to similar. A phase i, doseescalation study of the novel pololike. Volasertib is administered as a 350mg one hour intravenous iv infusion. Dohner, phase i ii study of volasertib bi 6727, an intravenous pololike kinase plk inhibitor, in patients with acute myeloid leukemia aml. Subsequent patients were randomized to volasertib n 37, volasertib with pemetrexed n 47, or pemetrexed n. Phase iii randomized trial of volasertib combined with low. Volasertib is an intravenously administered, smallmolecule cell cycle inhibitor of pololike kinase1 plk1, being developed by boehringer ingelheim for the. Volasertib may be effective in several malignancies evidenced by the fact that its target plk1 is overexpressed in up to 80% of malignancies, where it has been associated with a poorer treatment outcome and reduced overall survival. Pololike kinase 1 inhibitors and their potential role in. Publication of the phase i ii trial data that was used in support of the breakthrough therapy designation is expected later this year. These results prompted the initiation of multiple phase ii studies, including a randomized trial of volasertib as monotherapy or in combination with pemetrexed in secondline nsclc nct00824408. Volasertib is an investigational compound that inhibits enzymes called pololike kinase plk.
Boehringer ingelheim corporations volasertib wins fda. Boehringer ingelheim begins phase iii study of volasertib in. A phase i study of volasertib combined with afatinib, in advanced solid tumors. In a randomized, phase ii trial comparing lowdose cytarabine ldac with or without volasertib in patients with previously untreated aml ineligible for intensive therapy, volasertib plus ldac increased remission rate, improved survival, and had a clinically.
The phase i trial in adult patients found a maximum plasma concentration of 1210 nm at the recommended phase ii dose of 300 mg volasertib given as an intravenous infusion 24. The results of another phase i clinical trial enrolled 59 asian patients with advanced solid tumors has shown that. To determine the maximum tolerated dose mtd of volasertib, a pololike kinase inhibitor, combined with afatinib, an oral irreversible erbb family blocker, in patients with advanced solid tumors nct01206816. In the randomized phase ii part comparing ldac versus volasertib plus ldac, 87 patients were treated in two arms. The fda breakthrough designation was based on the results of a randomized phase ii study of volasertiblowdose cytarabine ldac versus ldac alone for patients with previously untreated aml who are ineligible for. The fda breakthrough designation was based on the results of a randomized phase ii study of volasertib lowdose cytarabine ldac versus ldac alone for patients with previously untreated aml who are ineligible for. A separate phase i trial in japanese patients with solid tumors is ongoing table 2. Boehringer ingelheim is committed to further investigating volasertib with a. Phase iii study of bi 6727 volasertib, an intravenous pololike kinase1 plk1 inhibitor, in patients with acute myeloid leukemia aml. Volasertib is a potent inhibitor of pololike kinase that induces mitotic arrest and apoptosis in cells undergoing mitosis.
Results of phase iii study of volasertib for the treatment. These safety results are as expected from the mode of action of volasertib and the underlying disease, and are also in line with what was expected from the phase iii trial in white patients with aml. Boehringer ingelheims investigational volasertib receives fda breakthrough therapy designation ridgefield, conn. Accordingly, multiple groups have investigated the combined anticancer effects of volasertib and other chemotherapeutic drugs in the preclinical and clinical studies.
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