asco@alo33:161846 / 0-8
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Background: Most patients pts ith anaplastic lymphoma kinase ALK and c-ros oncogene 1 ROS1 NSCLC develop resistance to tyrosine kinase inhibitor TKI therapy, ith the central nervous system CNS as a common site of relapse. Lorlatinib is a selective brain-penetrant ALKROS1 TKI active against most knon resistance mutations. Methods: In Ph. I of the ongoing Ph. III study NCT01970865, eligible pts had ALK+ or ROS1+ NSCLC ithithout brain metastases mets and ere treatment naxEF;ve or had disease progression after 1 TKIs. Pts received lorlatinib on day 7 and daily from day 1. Primary objective as to identify the MTD and recommended Ph. II dose RP2D . Other objectives ere safety and efficacy by RECIST v1.1, including intracranial activity. Results: Of 54 pts treated in Ph. I as of Nov 30 2015, 41 ere ALK+, 12 ROS1+; and 1 ith mutation status not recorded at cut-off date. Pts ere heavily pretreated:27 had received 1 prior TKI, 20 1 prior TKI and 7 ere TKI naxEF;ve; 39 pts had CNS mets at baseline. Pts ere treated across 10 dose levels 10200 mg . Response rates RR are shon in the Table. 29 pts remain on treatment. The most common treatment-related adverse events AEs ere hypercholesterolemia 54 percent and peripheral edema 37 percent . Hypercholesterolemia as the most common 9 percent grade G 3 treatment-related AE and most frequent reason for dose delayreduction. No pt discontinued due to a treatment-related AE. One DLT occurred in a pt ho received lt1621 planned 200 mg daily doses due to G2 CNS AEs. CSF concentrations in steady-state samples from 3 pts ith CNS mets shoed excellent penetration of lorlatinib into the CNS. Conclusions: Lorlatinib as ell tolerated and demonstrated durable clinical responses, including intracranial responses, in ALK+ including G1202R+ pts and ROS1+ NSCLC pts, many of hom had CNS mets and 1 prior TKIs. The RP2D as identified as 100 mg once daily. Ph. II is enrolling. Clinical trial information: lta href=http:clinicaltrials.govshoNCT01970865 NCT01970865ltth class=border-bottom align-left rospan=2 ltth class=border-bottom-broken colspan=1 Nltth class=border-bottom-broken colspan=1 CRltth class=border-bottom-broken colspan=1 uCRltth class=border-bottom-broken colspan=1 PRltth class=border-bottom-broken colspan=1 uPRltth class=border-bottom-broken colspan=1 Overall RRn percent Intracranial IC + extracranial522 4 1 2 22 42 1 2 26 50 IC target + nontarget lesions 368 22 2 6 4 11 2 6 16 44 IC target lesions 205 25 1 5 4 20 2 10 12 60 ltfn id=TF-161846-001-1 ltp class=mtgabstract-table-fn Abbreviations: CR, complete response; PR, partial response; U, unconfirmed.lttable-rap-foot ,J Clin Oncol 34, 2016 suppl; abstr 9009 ,NCT01970865,00:00.0,Raising the Bar for Targeted Therapies for Lung Cancers
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