[INNO-406 P1 in Ph+ CML and ALL]
>>A phase I study of INNO-406, a dual inhibitor of Abl and Lyn kinases, in adult patients with Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia (CML) or acute lymphocytic leukemia (ALL) relapsed, refractory, or intolerant of imatinib.
Abstract No:
7046
Citation:
Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 7046
Author(s):
A. R. Craig, H. M. Kantarjian, J. E. Cortes, D. Jones, A. Hochhaus, S. O'Brien, M. Rios, C. Zander, L. Gleich, E. P. Carroll, O. G. Ottmann
Abstract:
Background: INNO-406 is an orally available, dual Abl/Lyn kinase inhibitor that is up to 55-times more potent than imatinib in Bcr-Abl cell lines. Numerous Bcr-Abl mutant proteins (not T315I) are sensitive to INNO-406 in vitro. INNO-406 demonstrates specific Src kinase activity against Lyn kinase. Methods: In this phase I study, patients with imatinib-resistant or intolerant Philadelphia (Ph+) chromosome- positive leukemias were eligible for treatment with INNO-406 once a day, orally. Results: 14 pts [median age: 58 yrs (range 18-74); 7 male, 7 female; median CML duration: 53 mo. (range 14-266); and median time on imatinib 45 months (range 12-129); chronic phase CML (8 pts), accelerated phase CML (2 pts), blast phase CML (1 pt), Ph+ ALL (3 pts); previous treatment with nilotinib (5 pts), dasatinib (6 pts)] have been enrolled in the following dose cohorts (mg/day): 30 (3 pts), 60 (3), 120 (6) and 240 mg (2), and have been on treatment between 7 and 123 days. 3 pts remain on study; 10 pts discontinued with disease progression [data unmonitored]. 6 patients who have completed >1 month of treatment, 3 have evidence of clinical response. Patient 5, a chronic phase CML treated with imatinib for 69 mo. before developing resistant disease with an Y253H mutation, had a minimal cytogenetic response after 1 month of INNO-406 therapy. Patient 4, an accelerated phase CML treated with imatinib and nilotinib for 16 and 6 mo., respectively, before becoming intolerant to nilotinib due to thrombocytopenia, has maintained a complete hematologic response following 4.5 months of INNO-406 therapy at a dose of 120 mg/day. Patient 1, a chronic phase CML treated with imatinib for 51 mo. before developing resistant disease without a mutation, has maintained stable white cell counts after 4 months of therapy at a dose of 30-60 mg/day, with a 55-fold reduction in Bcr-Abl transcript levels after 1 month of INNO-406 therapy. Conclusions: INNO-406 is well tolerated in patients at a dose of 240 mg/day, with encouraging evidence of clinical activity in imatinib-resistant and nilotinib-intolerant patients. In the absence of dose limiting toxicity, dose escalation continues.<<
This gives me pause. I thought INO-406 DID hit the T315I mutant. Pretty sure SGX' competing compound does; if this is the case, no wonder it's a more expensive stock (though having more cash also helps!). And 10/14 patients discontinued due to progression, yikes. Do we reckon they were just treated too late in the game for anything to help?
clinicaltrials.gov
The trials is going to last one year and is wrapping up soon. CML trials are fast, all right. Strategy is apparently to do a pivotal P2 (a la bortezomib) later this year. Can't fault these guys for being slow.
Cheers, Tuck |
