LBA61 First analysis of RAIN-701: Study of tarloxotinib in patients with non-small cell lung cancer (NSCLC) EGFR Exon 20 insertion, HER2-activating mutations & other solid tumours with NRG1/ERBB gene fusions

Tarloxotinib is a hypoxia-activated prodrug of a pan-ErbB kinase inhibitor that releases a potent irreversible active metabolite (tarloxotinib-E) under hypoxic conditions to preferentially deliver the active moiety to tumor versus normal tissues. Tarloxotinib has shown preclinical efficacy in EGFR exon 20 and HER2 mutant non-small cell lung cancer (NSCLC) as well as other oncogenic alterations in the ERBB gene family such as NRG1 fusions. We report the first results of the RAIN-701 trial (NCT03805841). Patients (pts) with advanced NSCLC harboring an EGFR Exon 20 insertion (Cohort A) or HER2 activating mutation (Cohort B) with progressive disease after platinum-based chemotherapy or with any solid tumors harboring an NRG1, EGFR, HER2 or HER4 fusion (cohort C) were eligible. Enrollment was based on local genomic testing. Tarloxotinib was administered at 150 mg/m2 IV weekly. The primary endpoint is objective response rate per RECIST v1.1. As of June 12, 2020, 23 pts (11 cohort A, 11 cohort B, 1 cohort C) were treated with tarloxotinib. The disease control rate for all evaluable pts was 60% (12/20). In cohort A, the best response was stable disease (SD) in 6/11 (55%) and progressive disease (PD) in 5/11 (45%). In cohort B, 4/9 evaluable pts (44%) exhibited tumor reduction by RECIST and 2/9 pts experienced confirmed PR (22%), 4/9 (44%) pts had SD, and 3/9 (33%) pts had PD. Three pts in cohort B were treated beyond 6 months with 3 pts still ongoing. Most treatment emergent adverse events (TEAEs) were grade 1/2. Those occurring at >20% were prolonged QTc (60.9%), rash (43.5%), nausea (21.7%), and diarrhea (21.7%). The grade 3 TEAEs were prolonged QTc (34.8%), rash (4.3%), diarrhea (4.3%) and increased ALT (4.3%). Five of 23 (21.7%) pts required dose reduction and only 1/23 (4.3%) pts discontinued tarloxotinib due to a drug-related adverse event (infusion reaction). Tarloxotinib exhibits antitumor activity in NSCLC pts with HER2 activating mutations. Tarloxotinib was well tolerated and exhibited low rates of severe EGFR-related toxicities such as rash and diarrhea.