Clinical Trials

Date: 2017-06-05

Type of information: Presentation of results at a congress

phase: 1-2

Announcement: presentation of results at the American Society of Clinical Oncology (ASCO) annual meeting, in Chicago

Company: GlycoMimetics (USA - Md)

Product: GMI-1271

Action mechanism:

• E-selectin antagonist. GMI-1271 is designed to block E-selectin (an adhesion molecule on cells in the bone marrow) from binding with acute myeloid leukemia cells as a targeted approach to disrupting well-established mechanisms of leukemic cell resistance within the bone marrow microenvironment. Preclinical research points to the drug's potential role in moving cancerous cells out of the protective environment of the bone marrow where they hide and escape the effects of chemotherapy.
• GMI-1271 was granted Breakthrough Therapy designation from the FDA for the treatment of adult acute myeloid leukemia (AML) patients with relapsed/refractory disease. In addition, GMI-1271 has been granted orphan drug designation and Fast Track status by the FDA and Orphan Drug designation by the European Commission.

Disease: acute myeloid leukemia (AML)

Therapeutic area: Cancer - Oncology

Country: Australia, Ireland, USA

Trial details: The study will evaluate GMI-1271, a specific E-selectin antagonist, in acute myeloid leukemia in combination with standard agents used to treat this disease. This clinical trial is a multinational open-label study evaluating endpoints for safety, pharmacokinetics and efficacy of GMI-1271 in combination with induction chemotherapy in patients with high-risk AML. This trial is being conducted at a number of academic medical institutions in the United States, Ireland, and Australia. While the primary objective is to assess safety, additional endpoints include overall response rate, biomarkers of activity, durability of response and overall survival. The Phase 2 portion of the trial is expected to include approximately 25 participants over 18 years of age with relapsed or refractory AML and approximately 25 participants over 60 years of age who are newly diagnosed.(NCT02306291)

Latest news:

• • On June 5, 2017,  GlycoMimetics announced new and updated data from the Phase 2 portion of its ongoing Phase 1/2 clinical trial that showed high remission and low mortality rates of GMI-1271 being developed as a treatment for patients with acute myeloid leukemia. Clinical investigators are presenting the data today from 79 patients in the trial via posters and discussion at the 2017 annual meeting of the American Society for Clinical Oncology (ASCO) in Chicago.
• In this trial, patients treated with GMI-1271 together with standard chemotherapy continue to achieve higher than expected remission rates based on historical controls, as well as lower than expected induction-related mortality rates. Treatment also continues to be well tolerated in this patient population. Among the 54 relapsed/refractory AML patients participating in the trial for whom data is available:
• The overall response rate (complete remission/complete remission with incomplete marrow recovery, or CR/CRi) was 41 percent, which is higher than historical controls, and the 60-day induction related mortality rate was 7 percent, which is lower than historical controls.
• Oral mucositis, or inflammation with mouth ulcers that is a sign of adverse effects of chemotherapy, was seen at low rates and severity with only one Grade 3/4 event observed.
• The median overall survival time for Phase 1 trial patients was 7.6 months. Remissions were durable enough to allow 9 patients to receive stem cell transplants.
• For patients in the Phase 1 portion of the trial who responded with a remission, more than half survived for at least a year after treatment.
• Among the 25 newly diagnosed elderly patients (age 60 and older) participating in the trial for whom data is available:
• The overall response (CR/CRi) rate was 68 percent, with 73 percent in patients with de novo AML and 64 percent in patients with secondary AML. The 60-day mortality rate was 8 percent. There were no cases of grade 3 or 4 mucositis.
• For the 9 evaluable patients achieving CR/CRi, disease-free survival was 100% at 6 months after treatment.
• Data from the Phase 1/2 trial were submitted to the FDA.
• • On May 19, 2017, GlycoMimetics announced that it has completed enrollment of relapsed/refractory AML patient cohort in phase 2 portion of clinical trial of GMI-1271 . The trial is now fully enrolled with 91 patients: 25 in newly diagnosed arm and 66 in relapsed refractory arm. The study is designed to evaluate the potential of GMI-1271, an E-selectin antagonist drug candidate, in combination with chemotherapy, as a treatment for individuals with either newly diagnosed or relapsed/refractory AML. Enrollment in the study's first arm in newly diagnosed elderly AML patients was completed in the first quarter of this year. GlycoMimetics expects to submit interim study data for presentation at the American Society of Hematology (ASH) Annual Meeting in December 2017 .
• • On May 18, 2017, GlycoMimetics announced the release of abstracts containing new data from the ongoing Phase 2 clinical trial of  GMI-1271 in patients with acute myeloid leukemia (AML). The data will be presented at the June annual meetings of the American Society of Clinical Oncology (ASCO) and the European Hematology Association (EHA). The data released by ASCO and EHA, which reflect a late-January analysis, will be updated in posters presented at both meetings. In the ongoing Phase 2 trial, AML patients treated with GMI-1271, combined with chemotherapy, continue to experience higher-than-expected remission rates and lower-than-expected induction-related mortality rates in both arms of the trial. In addition, researchers have observed that baseline expression of the E-selectin ligand biomarker on leukemia cells was predictive of clinical response and tied to greater likelihood of achieving remission in the cohort of AML patients with relapsed/refractory disease, which supports the mechanism of action of GMI-1271. Treatment with GMI-1271 continues to be well tolerated, with no obvious incremental toxicity observed when GMI-1271 is added to chemotherapy.Consistent with GlycoMimetics' prior published research, the addition of GMI-1271 to mitoxantrone, etoposide and cytarabine (MEC) chemotherapy has been well-tolerated, with patients achieving a high overall response rate (ORR), low induction mortality, and promising initial survival outcomes. The data show that baseline expression of the E-selectin ligand biomarker was predictive of response. GlycoMimetics believes these results are better than what would be expected in this population, based on published historical controls in similar patients.
• Highlights of the data reported in the published abstract include:
• 47 patients were enrolled.
• 30- and 60-day mortality were 0 and 7%, respectively.
• ORR was 21/42 evaluable (50%).
• Median Overall Survival in the Phase 1 portion was 7.6 months. The median E-selectin ligand binding at baseline was 35% of blasts (range, 1-75%) and, importantly, was higher in those achieving remission. The data from the ongoing Phase 2 trial were submitted to the FDA.
• • On March 7, 2017, GlycoMimetics announced that the first of two patient cohorts in its Phase 2 acute myeloid leukemia trial of GMI-1271 has completed enrollment. This cohort is comprised of 25 patients 60 years of age or older with newly diagnosed AML. Enrollment in the study's second arm is expected to complete in the middle of this year. The two arms combined will enroll a total of about 90 patients.
• • On December 5, 2016, GlycoMimetics announced that results of its Phase 1/2 clinical trial on GMI-1271 continued to show high rates of remission and favorable tolerability among study participants with acute myeloid leukemia. The data are being shared today via a poster at the 58th American Society of Hematology (ASH) Annual Meeting and Expo in San Diego. The company's E-selectin antagonist, GMI-1271, showed significant progress in the Phase 1/2 clinical trial. For a total of 33 study participants with relapsed or refractory disease in one arm of the trial, the complete response (CR) rate was 45 percent. For 11 newly diagnosed study participants 60 or more years of age in the second arm of the trial, the CR rate was 73 percent. Thus, all study participants evaluated to date who have responded have had complete remissions; there have been no patients observed who responded with incomplete count recoveries (CRi). In addition, in elderly, newly diagnosed patients evaluated to date, the 60-day mortality rate was zero for those receiving intensive induction chemotherapy plus GMI-1271. The results presented at the ASH meeting expand on data presented at the European Hematology Association 21st Congress in Copenhagen, Denmark, in June 2016 (See below).
• • On June 28, 2016, GlycoMimetics announced dosing of the first patient with newly diagnosed acute myeloid leukemia (AML) in the Phase 2 portion of its ongoing Phase 1/2 study evaluating its novel E-selectin antagonist, GMI-1271, combined with chemotherapy. This Phase 2 portion of the study in newly diagnosed patients is expected to include approximately 25 participants.  For the study's Phase 2 portion, the optimal dose of GMI-1271 has been determined, and in this arm of the study clinical investigators will study the effects on newly diagnosed patients receiving the drug candidate to obtain additional safety and efficacy data. Study enrollment in this arm is limited to patients at least 60 years of age who have been newly diagnosed with AML and are eligible to receive treatment with the chemotherapy agents cytarabine and idarubicin (‘7+3'). All patients must be eligible to receive this intensive chemotherapy regimen, and will be given GMI-1271 in addition to this combination chemotherapy. During the Phase 1 portion of the study, patients received a single cycle of treatment including GMI-1271. During this Phase 2 portion, certain patients will be eligible to receive additional cycles of treatment.
• • On June 10, 2016, GlycoMimetics announced data from the Phase 1 portion of its Phase 1/2 clinical trial of GMI-1271, combined with induction chemotherapy, in patients with relapsed/refractory acute myeloid leukemia. Dose escalation is complete and a GMI-1271 dose was identified for Phase 2 testing. The results, presented at the European Hematology Association 21st Congress in Copenhagen, Denmark, showed an overall response rate (combined complete remission (CR) and remission with incomplete recovery (CRi)) of 47 percent among 19 patients, including those who were older than 60 years of age, with primary refractory or relapsed disease, poor cytogenetic risk factors including FLT-3 ITDs, and/or extramedullary disease. Eight of the 19 patients achieved a best clinical response of CR, one patient achieved CRi, and one patient achieved morphologic leukemia-free state (MLFS). Five of the 19 patients went on to receive a hematopoietic stem cell transplant. There was no mortality reported during the treatment phase of 44 days, and no dose-limiting toxic reactions were observed among participants. Pharmacokinetic (PK) data showed a dose-dependent increase in plasma concentrations of GMI-1271, above levels associated with anti-leukemic activity in animal models of AML. In addition, biomarker analysis confirmed on-target activity for GMI-1271 at all dose levels. During dose escalation, patients received only one cycle of treatment with GMI-1271. As part of the Phase 2 expansion, certain patients will be eligible to receive more than one cycle of treatment. The poster (P191) is entitled "Results of a Phase 1 study of GMI-1271, a potent E-selectin antagonist in combination with induction chemotherapy in relapsed/refractory AML: a novel, well-tolerated regimen with a high remission rate".
• • On June 6, 2016, GlycoMimetics announced dosing of the first patient with relapsed/refractory acute myeloid leukemia in the Phase 2 portion of its ongoing Phase 1/2 clinical trial evaluating GMI-1271, combined with induction chemotherapy.
• For the study's Phase 2 portion, the optimal dose has been determined, and clinical investigators will expand the number of patients receiving GMI-1271 to obtain additional safety and efficacy data. Study enrollment is limited to patients at least 18 years old with relapsed or refractory AML and who would be treated with mitoxantrone, etoposide, and cytarabine. All patients must be eligible to receive this chemotherapy regimen, and will be given GMI-1271 in addition to this combination chemotherapy. During the Phase 1 portion of the study, patients received a single cycle of treatment including GMI-1271. During this Phase 2 portion, certain patients will be eligible to receive an additional cycle of treatment.
• • On March 2, 2016, GlycoMimetics announced that of the first 13 evaluable patients in its clinical trial of GMI-1271 in combination with chemotherapy in patients with relapsed/refractory acute myeloid leukemia, investigators have observed clinical responses in eight patients, for an overall response rate of 62%. Of the eight objective responses, seven patients achieved a complete response (CR), with the eighth patient achieving complete response but with an incomplete blood count recovery (CRi). GMI-1271 was also well tolerated in this group of 13 patients. The detailed findings have been submitted to a major scientific meeting.

     

Is general: Yes