P3.02c-027 Phase I and PK Study of the Folate Receptor-Targeted Small Molecule Drug Conjugate (SMDC) EC1456 in Advanced Cancer: Lung Cancer Subset: Topic: IT

Abstract

EC1456 is composed of folic acid conjugated through a releasable linker system to a potent microtubule inhibitor, tubulysin B hydrazide. EC1456 targets folate receptor (FR)-expressing cancer cells, which occur in approximately 60% of NSCLC cases and 14% of SCLC. The objectives of the ongoing Phase 1 are to determine the safety, PK, and optimal dosing schedule of EC1456 in advanced cancer pts. FR expression (not required for enrollment) is characterized in all pts using 99mTc-etarfolatide. 63 pts were dosed weekly (QW) or twice-weekly (BIW), for 2 consecutive weeks of a 3-week cycle. 8 NSCLC and 3 SCLC pts received doses ranging from 1.0-12.5 mg/m2. Toxicities are primarily Grade (Gr) 1 and 2. Common adverse events (AE) are GI, fatigue, and metabolic changes. Gr 3 infusion reaction (4.5 mg/m2) and Gr 3 headache (10.0 mg/m2) were seen in the QW cohort. The safety profile in lung cancer pts was similar to the overall population.Tabled 1BIW (N=32)QW (N=31)BIW Lung (N=4)QW Lung (N=7)AllDrug RelatedAllDrug RelatedAllDrug RelatedAllDrug Related≥ 1 AE32 (100%)25 (78%)29 (94%)23 (74%)4 (100%)4 (100%)7 (100%)4 (57%)≥ 1 grade 3 or 4 AE19 (59%)6 (19%)14 (45%)4 (13%)2 (50%)0 (0%)1 (14%)0 (0%)≥ 1 serious AE12 (38%)2 (6%)14 (45%)5 (16%)1 (25%)0 (0%)2 (29%)0 (0%)Serious drug related AEsConstipation (2/63 pts); Abd pain, Anemia, Headache, Infusion reactions, and SVT(1/63 pts each) Open table in a new tab Response and durability of response is demonstrated in the figure: EC1456 is well tolerated, with early indications of efficacy suggested by durable stable disease, and responses in this refractory population. Updated safety, PK, and efficacy data will be presented at the meeting.