Date: 2017-12-09
Type of
information: Presentation of results at a congress
phase: 1
Announcement: presentation of results at the 59th American Society of Hematology (ASH) Annual Meeting
Company: immunogen (USA - MA)
Product: IMGN779
Action
mechanism:
- antibody drug conjugate (ADC). IMGN779 comprises a CD33-targeting antibody with a potent DNA-alkylating agent, the IGN DGN462, attached. IMGN779 is the first ADC to utilize one of ImmunoGen's new family of indolino-benzodiazepine cancer-killing agents, which the Company calls IGNs. DNA-alkylating IGNs have been designed to be ultra-potent, yet provide the tolerability necessary for ongoing retreatment. This new class of cancer-killing agent has been developed by ImmunoGen for use in ADCs. Ultra -potent, these DNA-alkylating indolino-benzodiazepines are expected to extend the types of cancers able to be effectively treated with ADC therapies beyond those addressable with ImmunoGen's tubulin-acting agents. Such cancers can include ones insensitive to tubulin-acting agents and/or with reduced antigen expression.
Disease: acute myeloid leukemia, refractory acute myeloid leukemia
Therapeutic
area: Cancer - Oncology
Country: USA
Trial
details:
- This open label, multicenter Phase 1 study is designed to establish the maximum tolerated dose and determine the recommended Phase 2 dose for IMGN779 administered as monotherapy. The trial is also intended to evaluate safety and tolerability and characterize PK, PD, and preliminary anti-leukemia activity in relapsed or refractory AML. (NCT02674763)
Latest
news:
- • On December 9, 2017, ImmunoGen announced that new data from the ongoing Phase 1 study of IMGN779, a next-generation CD33-targeting antibody drug conjugate, in patients with relapsed or refractory adult acute myeloid leukemia were presented at the 59th American Society of Hematology (ASH) Annual Meeting in Atlanta.
- The Phase 1 data presented at ASH demonstrate that IMGN779 was well-tolerated with no dose-limiting toxicities (DLTs) observed in patients with relapsed or refractory acute myeloid leukemia across nine dose levels administered once every two weeks (Q2W) and one dose level administered once a week (QW). In addition, anti-leukemia activity was seen at doses ?0.39 mg/kg in both schedules in patients with poor prognostic features. The maximum tolerated dose has not been reached and dose escalation continues. Data across the first seven dose levels on the Q2W schedule were presented in June at the 22nd Congress of the European Hematology Association (EHA). Key findings presented from the Phase 1 study of IMGN779 at ASH (Abstract #1312) include the following: IMGN779 displays a tolerable safety profile.No DLTs were observed on either administration schedule at doses examined - up to 0.91 mg/kg Q2W and 0.39 mg/kg QW. No increase in the nature, frequency, or severity of any treatment-emergent adverse event was observed with increasing dose. This profile has enabled repeat dosing, with one patient showing a 93% reduction in bone marrow blasts with extended treatment and who remains on therapy through Cycle 14. Pharmacokinetic (PK) exposures and pharmacodynamic (PD) CD33 saturation continue to increase with dose, and support further escalation and exploration of both the QW and Q2W schedules. Anti-leukemia activity was seen at doses ?0.39 mg/kg in both schedules with 16 of 17 patients showing a decrease in peripheral blasts within 10 days after first dose with a median maximal decrease of 71%. Seven of 17 patients showing a 48%-96% reduction in bone marrow blasts. These seven patients had poor prognostic features (e.g., prior intense therapy, primary refractory disease, RAS/TP53/FLT3/IDH mutations).
- This ongoing Phase 1 trial is designed to establish the maximum tolerated dose and determine the recommended Phase 2 dose for IMGN779 administered as monotherapy. The trial is also intended to evaluate safety and tolerability, and characterize PK, PD, and preliminary anti-leukemia activity in relapsed or refractory AML.
• On June 26, 2017, ImmunoGen presented data from the ongoing Phase 1 study evaluating single agent IMGN779 in patients with relapsed or refractory adult acute myeloid leukemia whose tumors express CD33. The first-in-human data demonstrate the safety and tolerability of IMGN779 across seven dose levels, with no dose limiting toxicities (DLTs), as well as evidence of dose-dependent biological and anti-leukemia activity. These results were presented in a poster presentation on Saturday, June 24, 2017, at the 22nd Congress of the European Hematology Association (EHA) in Madrid, Spain.
- Safety, pharmacokinetic (PK), and pharmacodynamic (PD) data, as well as initial anti-leukemia activity for IMGN779 through dose level seven were presented at EHA. Key findings included:
- - No DLTs have been observed through dose level seven, with reported adverse events consistent with the underlying disease.
- - No increase in the nature, frequency, or severity of any treatment-emergent adverse event has been reported with escalating doses and no evidence of cumulative toxicity has been observed with repeated dosing.
- - Favorable PK/PD reveal prolonged exposure and CD33 saturation at dose levels six and seven.
- Initial anti-leukemia activity was observed at dose levels six and seven in patients who failed intensive frontline therapy.
- Preclinical data for IMGN779 were also presented at EHA showing the agent is highly active in multiple AML xenograft models and is well-tolerated in preclinical repeat dosing regimens. (Poster Details: Initial results from a first-in-human study of IMGN779, a CD33-targeting antibody-drug conjugate (ADC) with novel DNA alkylating activity, in patients with relapsed or refractory AML. Abstract: P526).
- Findings from the preclinical evaluation provided the foundation for the clinical evaluation of IMGN779 in AML.
- • On April 18, 2016, ImmunoGen announced the start of clinical testing of IMGN779 product candidate for the treatment of acute myeloid leukemia, a CD33-positive cancer. The IMGN779 Phase 1 trial in CD33-positive AML will assess two alternative dosing schedules - weekly and biweekly administration - concurrently in its dose-finding stage. The selected dose and schedule will then be used in the two planned expansion cohorts: one assessing IMGN779 in patients with AML in first relapse and one assessing it in patients with relapsed/refractory acute myeloid leukemia.
Is
general: Yes
