Latest news with #NPM1
Business Insider
6 days ago
- Business
- Business Insider
Kura Oncology says ‘positive' results from KOMET-001 Phase 2 trial of ziftomenib
Kura Oncology (KURA) announced the presentation of positive pivotal results from the KOMET-001 Phase 2 registration-directed trial of ziftomenib, a once-daily, oral investigational menin inhibitor, in patients with relapsed/refractory NPM1-mutant acute myeloid leukemia in an oral session at the 2025 American Society of Clinical Oncology Annual Meeting being held in Chicago, IL from May 30 – June 3, 2025. 'We are delighted to announce positive pivotal data from the KOMET-001 trial in R/R NPM1-mutated AML patients treated with ziftomenib,' said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. 'NPM1 mutations are among the most common in AML, representing approximately 30% of cases, and there are no FDA-approved therapies specifically for this patient population. With these encouraging results and a PDUFA target action date of November 30, 2025, we and our partners at Kyowa Kirin look forward to supporting FDA with its review of the ziftomenib New Drug Application and are well-positioned to meaningfully impact relapsed or refractory patients with NPM1 mutations.' The KOMET-001 Phase 2 population included 92 adult patients with R/R NPM1-m AML. The median age was 69. Patients were heavily pretreated, with 33% having received three or more prior lines of therapy (median prior lines: 2) and 59% having been previously treated with venetoclax. A complete remission plus CR with partial hematological recovery rate of 23% was observed among patients with R/R NPM1-m AML in the Phase 2 portion of the KOMET-001 trial. Among those 21 patients who achieved CR/CRh, 13 had a CR and 8 had a CRh. The median duration of CR/CRh responses was 3.7 months and the restricted mean duration of response was 4.3 months at the time of the data cutoff. MRD status was assessed in 19 of 21 patients who achieved CR/CRh, and 63% of these patients were MRD-negative. Comparable CR/CRh rates were observed across pre-specified subgroups, regardless of prior HSCT, prior venetoclax or FLT3/IDH co-mutations. Additional patient benefit beyond CR/CRh was observed with a rate of transfusion conversion of 21% and a rate of maintenance of transfusion independence of 20%. A median OS of 16.4 months was observed for responders and a median overall survival of 3.5 months was observed among non-responders. The safety population included 112 adult patients with R/R NPM1-m AML from the pooled Phase 1b and Phase 2 portions of the KOMET-001 trial. The safety profile observed with ziftomenib in this population was consistent with previously reported data. Treatment-related adverse events led to treatment discontinuations in 3% of patients. TRAEs of Grade greater than or equal to3 which occurred in more than 10% of patients were limited to differentiation syndrome, which was well managed by protocol-specified mitigation strategies and no Grade 4/5 treatment-related DS was observed. Although QTc prolongation was reported in three patients per investigator assessment, all three patients were on concomitant medications associated with QTc prolongation, two had electrolyte abnormalities and one had a prior diagnosis of atrial fibrillation.
The Star
13-05-2025
- Health
- The Star
Acute myeloid leukaemia: New test improves survival time
A highly sensitive test that detects traces of disease in the bone marrow of patients with a rare and aggressive type of blood cancer could help double their chances of survival, a first-of-its-kind trial has found. The 10-minute procedure – which involves an injection in the hip bone every three months – identified signs of acute myeloid leukaemia (AML) returning in patients before it showed in blood tests. This gives medics a 'window of opportunity' to treat people while they are still well, researchers said. Experts hope the test could become routine care for patients with AML. Detecting low levels AML is a cancer that causes the bone marrow to produce a large number of abnormal blood cells, with tens of thousands of people diagnosed with it around the world each year. The risk of developing the disease increases with age and it is most common in people over 75. After treatment, patients are usually seen every few weeks for blood tests. Trial chief investigator and Britain's Guy's and St Thomas' NHS Foundation Trust honorary consultant haematologist Professor Dr Nigel Russell said: 'There's a significant risk for these patients that the leukaemia is going to come back again, and that's normally detected by a deterioration in the blood tests. 'Sometimes it can happen very quickly, and sometimes it can happen over a period of weeks. 'So normally, the patient comes along, has a blood test done, the blood test is okay, they're sent off again. 'That's the procedure that's been the case for many years. 'But the trial included these extra tests in the bone marrow every three months to detect if there's any evidence of what we call residual leukaemia; it's such a low level that the blood tests are normal, but the disease can still be present at very low levels in the bone marrow.' The bone marrow test takes around 10 minutes and is performed under local anaesthetic, with a hollow needle inserted into the patient's hip bone to take the sample. 'It detects the RNA present in the leukaemia cells, but not present in normal cells,' Prof Russell added. Starting treatment while well For the study, led by King's College London and published in The Lancet Haematology journal, patients were screened for mutations in the NPM1 and FLT3 genes, which are common in younger people with AML. The trial involved 637 people who were in remission from AML and had, over three years, either received standard monitoring or standard monitoring with additional bone marrow tests every three months. Prof Russell said: 'It was about one-third of patients that really benefited from this approach that had a doubling of their survival, which was a massive improvement in outcome for these patients. 'And really, it's quite a simple extra procedure to have done. 'Since the results of the trial have become available, this sort of technology is now part of what we call the standard of care. 'The important thing is that it gives you a window of opportunity to treat the patient before they become unwell. 'Because if the patient relapses, they can become quite unwell very quickly and their blood counts are very abnormal. 'They have to come into hospital and they have to have further treatment of chemotherapy, and then possibly go on to a bone marrow transplant. 'The advantage of detecting it early is the patients can have these treatments when they're still well – even potentially as an outpatient, because their blood tests are normal. 'They don't need to come into hospital as an emergency and they're starting with a fresh start really, rather than being ill again.' Giving more time Jane Leahy, 51, from Wimbledon, London, is one of the patients who took part in the trial. She was diagnosed with AML in December 2014 at the age of 41, and after chemotherapy, went into remission the following April. The mother-of-two had her bone marrow tested as part of the trial, which picked up abnormalities a few months later. After restarting treatment, the bone marrow test results also showed the chemotherapy was not working, with a stem cell transplant her only chance of going into remission again. 'Without testing, I wouldn't have gone on to have my transplant, because my blood showed I was still in remission,' she said. Nine years after her bone marrow transplant – which was donated by her sister – Leahy is still in remission. She added: 'It's pretty scary really, when I think about potentially what could have happened. 'And there were so many things throughout my treatment journey, it felt like the stars were aligning. 'I feel incredibly lucky.' Leahy said bone marrow testing gives doctors 'more time', adding: 'The time is always critical, because it's so acute and so aggressive. 'And a lot of people die from AML before they get to treatment, because it's just diagnosed so late. 'So it just gives more time, more opportunities to try different treatment approaches and pick it up earlier, before it becomes too late to do anything about.' – PA Media/dpa
The Independent
29-04-2025
- Health
- The Independent
Blood cancer survival odds could be ‘doubled' as bone marrow test trial is a success
Patients with a rare and aggressive type of blood cancer could soon have their chances of survival doubled as a groundbreaking trial to detect the disease earlier concludes. Scientists working on the trial developed a highly sensitive test that that spots traces of disease in the bone marrow of patients to identify of acute myeloid leukaemia (AML). The 10-minute procedure – which involves an injection in the hip bone every three months – was able to identify signs of AML returning in patients before it showed in blood tests. This gives medics a 'window of opportunity' to treat people while they are still well, researchers said. Experts hope the test could become routine care for patients with acute myeloid leukaemia (AML) in the UK and beyond. AML is a cancer which causes the bone marrow to produce a large number of abnormal blood cells and around 3,100 people are diagnosed in the UK each year. The risk of developing the disease increases with age and it is most common in people over 75. After treatment, patients are usually seen every few weeks for blood tests. Professor Nigel Russell, honorary consultant at Guy's and St Thomas' NHS Foundation Trust and chief investigator on the trial, said: 'There's a significant risk for these patients that the leukaemia is going to come back again, and that's normally detected by a deterioration in the blood tests. 'Sometimes it can happen very quickly, and sometimes it can happen over a period of weeks. 'So normally, the patient comes along, has a blood test done, the blood test is okay, they're sent off again. That's the procedure that's been the case for many years. 'But the trial included these extra tests in the bone marrow every three months to detect if there's any evidence of what we call residual leukaemia; it's such a low level that the blood tests are normal, but the disease can still be present at very low levels in the bone marrow.' The bone marrow test takes around 10 minutes and is performed under local anaesthetic, with a hollow needle inserted into the patient's hip bone to take the sample. 'It detects the the RNA present in the leukaemia cells, but not present in normal cells,' Prof Russell added. For the study, led by King's College London and published in The Lancet Haematology, patients were screened for mutations in the NPM1 and FLT3 genes, which are common in younger people with AML. The trial involved 637 people who were in remission from AML who, over three years, either received standard monitoring or standard monitoring with additional bone marrow tests every three months. Prof Russell said: 'It was about one third of patients that really benefited from this approach that had a doubling of their survival, which was a massive improvement in outcome for these patients. 'And really, it's quite a simple extra procedure to have done. Since the results of the trial have become available, this sort of technology is now part of what we call the standard of care. 'The important thing is that it gives you a window of opportunity to treat the patient before they become unwell. 'Because if the patient relapses, they can become quite unwell very quickly, and their blood counts are very abnormal. 'They have to come into hospital, and they have to have further treatment of chemotherapy, and then possibly go on to a bone marrow transplant. 'The advantage of detecting it early is the patients can have these treatments when they're still well. Even potentially as an outpatient, because their blood tests are normal. 'They don't need to come into hospital as an emergency and they're starting with a fresh start, really, rather than being ill again.' Jane Leahy, 51, from Wimbledon, is one of the patients who took part in the trial. She was diagnosed with AML in December 2014, at the age of 41, and after chemotherapy went into remission the following April. The mother-of-two had her bone marrow tested as part of the trial, which picked up abnormalities a few months later. After restarting treatment, the bone marrow test results also showed the chemotherapy was not working, with a stem cell transplant her only chance of going into remission again. 'Without testing, I wouldn't have gone on to have my transplant, because my blood showed I was still in remission,' Mrs Leahy told PA. Nine years after her bone marrow transplant – which was donated by her sister – Mrs Leahy is still in remission. She added: 'It's pretty scary, really, when I think about potentially what could have happened. And there were so many things throughout my my treatment journey, it felt like the stars were aligning. 'I feel incredibly lucky.' Mrs Leahy said bone marrow testing gives doctors 'more time', adding: 'The time is always critical, because it's so acute and so aggressive. 'And a lot of people die from AML before they get to treatment, because it's just diagnosed so late. 'So it just gives more time, more opportunities to try different treatment approaches and pick it up earlier, before it becomes too late to do anything about.' Dr Richard Dillon, a clinical senior lecturer in cancer genetics from King's College London, said: 'Acute myeloid leukaemia is the most aggressive form of blood cancer, so knowing early that a patient's cancer is going to relapse is crucial for planning their treatment. 'We hope that these tests become part of routine care for this type of cancer across the UK and worldwide, and ultimately improve long-term survival rates for patients.' Laura Challinor, from the Blood Cancer UK charity, which part-funded the study, said the findings 'could help shift the dial in a positive direction'. She added: 'As this involves a bone marrow test every three months, we must also continue to push ahead with research into kinder therapies for the 280,000 people with blood cancer in the UK.'
Associated Press
20-02-2025
- Business
- Associated Press
Aptose Announces Positive Clinical Safety Review Committee (CSRC) Approval to Dose Escalate in Phase 1/2 Tuscany Trial of Frontline Triple Drug Therapy with Tuspetinib Amid Complete Responses and Favorable Safety in First Cohort
TUS+VEN+AZA triplet achieves complete responses (CRs) in difficult-to-treat TP53-mutated/CK AML and FLT3-wildtype AML patients, including a measurable residual disease (MRD) negative remission Dosing of initial 40 mg cohort complete; no prolonged myelosuppression or dose-limiting toxicities No dose reductions to the standard-of-care components of the regimen (AZA/VEN) in first cohort CSRC endorses escalation to 80 mg dosing, enrollment is open SAN DIEGO and TORONTO, Feb. 20, 2025 (GLOBE NEWSWIRE) -- Aptose Biosciences Inc. ('Aptose' or the 'Company') (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing the tuspetinib (TUS)-based triple drug frontline therapy to treat patients with newly diagnosed AML, today announced that the Cohort Safety Review Committee (CSRC) monitoring Aptose's Phase 1/2 TUSCANY trial of tuspetinib in combination with standard of care dosing of venetoclax and azacitidine (TUS+VEN+AZA triplet) has unanimously approved escalating from 40 mg TUS to 80 mg TUS based on its favorable review of data from the first four patients in the trial. The TUS+VEN+AZA triplet is being developed as a frontline therapy to treat large, mutationally diverse populations of newly diagnosed AML patients who are ineligible to receive induction chemotherapy. No significant safety concerns or dose limiting toxicities (DLTs) have been reported, including no prolonged myelosuppression of subjects in remission. All four subjects treated in the 40 mg cohort remain on study while enrollment is open for the 80 mg cohort. 'With a high level of enthusiasm, our CSRC - comprised of study investigators that include key leaders in the development of therapeutic agents for AML - recommended we escalate dosing in our TUSCANY trial with tuspetinib,' said Rafael Bejar, M.D., Ph.D., Chief Medical Officer of Aptose. 'The lack of prolonged myelosuppression with no DLT's and several complete responses, including an MRD-negative CRh noted early in treatment, is truly encouraging. As one our chief investigators remarked, if the TUS+VEN+AZA triplet shows efficacy and tolerability in difficult-to-treat AML populations with little myelosuppression, tuspetinib could be a game changer for frontline AML treatment.' TUSCANY: TUS+VEN+AZA Triplet Phase 1/2 Study Tuspetinib based TUS+VEN+AZA triplet therapy is being advanced in the TUSCANY Phase 1/2 trial with the goal of creating an improved frontline therapy for newly diagnosed AML patients that is active across diverse AML populations, durable, and well tolerated. Earlier APTIVATE trials of TUS as a single agent and in combination as TUS+VEN demonstrated favorable safety and broad activity in diverse relapsed or refractory (R/R) AML populations that went beyond the more prognostically favorable NPM1 and IDH mutant subgroups. Responses to TUS were also observed in those with prior-VEN and prior-FLT3 inhibitor (FLT3i) therapies, those with highly adverse TP53 and RAS mutations, and those with mutated or unmutated (wildtype) FLT3 genes. The TUSCANY triplet Phase 1/2 study is designed to test various doses and schedules of TUS in combination with standard dosing of AZA and VEN for patients with AML who are ineligible to receive induction chemotherapy. A convenient, once daily oral agent, TUS will be administered in 28-day cycles, beginning at 40 mg once daily, with dose escalations planned after a safety review of each dose level. Multiple U.S. sites are enrolling in the TUSCANY trial with anticipated enrollment of 18-24 patients by mid-late 2025. Data will be released as it becomes available. In January 2025, Aptose announced the initiation of the TUSCANY trial and dosing in the first cohort of newly diagnosed AML patients with the lowest starting dose (40 mg) of TUS as part of the TUS+VEN+AZA triplet, and the early data reveal promising clinical safety and antileukemic activity: To date, four newly diagnosed AML patients have received the lowest dose of TUS (40 mg) as part of the (TUS+VEN+AZA) combination. Three patients with unmutated (wildtype) FLT3 (FLT3-WT) completed Cycle 1 of treatment with no dose-limiting toxicities (DLTs) and no TUS dose adjustments. Two FLT3-WT patients achieved complete remissions (CR and CRh) by the end of Cycle 1. Notably, a patient with biallelic TP53 mutations and a complex karyotype obtained CR. The third FLT3-WT patient experienced significant reductions in bone marrow leukemic blasts during Cycle 1 and remains on therapy in Cycle 2. The fourth patient, harboring FLT3-ITD and NPM1 mutations, is currently dosing in Cycle 1 and is not yet eligible for response evaluation. Pharmacokinetic (PK) analyses for TUS show plasma levels unaffected by the addition of AZA, providing predictability and avoiding the need for dose alterations due to PK interactions. Similarly, VEN plasma levels in Cycle 1 are consistent with published results and the prior TUS/VEN APTIVATE study in R/R AML, indicating no clinically significant interactions with TUS. More information on the TUSCANY Phase 1/2 study can be found on ( here). About Aptose Aptose Biosciences is a clinical-stage biotechnology company committed to developing precision medicines addressing unmet medical needs in oncology, with an initial focus on hematology. The Company's lead clinical-stage, oral kinase inhibitor tuspetinib (TUS) has demonstrated activity as a monotherapy and in combination therapy in patients with relapsed or refractory acute myeloid leukemia (AML) and is being developed as a frontline triplet therapy in newly diagnosed AML. For more information, please visit Forward Looking Statements This press release may contain forward-looking statements within the meaning of Canadian and U.S. securities laws, including, but not limited to, statements relating to the therapeutic potential and safety profile of tuspetinib (including the triplet therapy) and its clinical development, the anticipated enrollment rate in the TUSCANY trial and the timing thereof, as well as statements relating to the Company's plans, objectives, expectations and intentions and other statements including words such as 'continue', 'expect', 'intend', 'will', 'should', 'would', 'may', and other similar expressions. Such statements reflect our current views with respect to future events and are subject to risks and uncertainties and are necessarily based upon a number of estimates and assumptions that, while considered reasonable by us are inherently subject to significant business, economic, competitive, political and social uncertainties and contingencies. Many factors could cause our actual results, performance or achievements to be materially different from any future results, performance or achievements described in this press release. Such factors could include, among others: our ability to obtain the capital required for research and operations and to continue as a going concern; the inherent risks in early stage drug development including demonstrating efficacy; development time/cost and the regulatory approval process; the progress of our clinical trials; our ability to find and enter into agreements with potential partners; our ability to attract and retain key personnel; changing market conditions; inability of new manufacturers to produce acceptable batches of GMP in sufficient quantities; unexpected manufacturing defects; and other risks detailed from time-to-time in our ongoing quarterly filings, annual information forms, annual reports and annual filings with Canadian securities regulators and the United States Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should the assumptions set out in the section entitled 'Risk Factors' in our filings with Canadian securities regulators and the United States Securities and Exchange Commission underlying those forward-looking statements prove incorrect, actual results may vary materially from those described herein. These forward-looking statements are made as of the date of this press release and we do not intend, and do not assume any obligation, to update these forward-looking statements, except as required by law. We cannot assure you that such statements will prove to be accurate as actual results and future events could differ materially from those anticipated in such statements. Investors are cautioned that forward-looking statements are not guarantees of future performance and accordingly investors are cautioned not to put undue reliance on forward-looking statements due to the inherent uncertainty therein. For further information, please contact: Aptose Biosciences Inc. 201-923-2049
