Mobocertinib (TAK-788) in <i>EGFR</i> exon 20 insertion (ex20ins)+ metastatic NSCLC (mNSCLC): Additional results from platinum-pretreated patients (pts) and EXCLAIM cohort of phase 1/2 study.
Suresh S. Ramalingam, Caicun Zhou, Tae Min Kim, Sang‐We Kim, James Chih‐Hsin Yang, Gregory J. Riely, Tarek Mekhail, Danny Nguyen, M.R. García Campelo, Enriqueta Felip, Sylvie Vincent, Shu Jin, Veronica Bunn, Jianchang Lin, Huamao Mark Lin, Minal Mehta, Pasi A. Jänne
Abstract
9014 Background: No approved targeted therapies are available for EGFR ex20ins+ mNSCLC. Mobocertinib, a first-in-class, potent, oral TKI targeting EGFR ex20ins mutations, has Breakthrough Therapy Designation in the US and China for post-platinum-based chemotherapy pts with EGFR ex20ins+ mNSCLC. Methods: This 3-part, open-label, multicenter study (NCT02716116) has dose-escalation/expansion and extension (EXCLAIM) cohorts. Pts with EGFR ex20ins+ mNSCLC, ECOG status 0–1, and ≥1 prior line of therapy for locally advanced/metastatic disease received mobocertinib 160 mg QD. Primary endpoint was confirmed objective response rate (ORR; RECIST v1.1) assessed by independent review committee (IRC). We present additional efficacy and safety data for 114 platinum-pretreated pts (PPP) and 96 pts from EXCLAIM safety cohort. Results: Results are from Nov 1, 2020, data cutoff. Among PPP pts (n=114; median age 60 y [27–84 y]), 66% were female, 60% were Asian, and 59% had ≥2 prior systemic anticancer lines. Confirmed ORR per IRC was 28%, including 1 complete response (CR); disease control rate (DCR) was 78% [95% CI: 69–85]; median duration of response (DOR) was 17.5 mo (Table). In EXCLAIM (n=96; median age 59 y [27–80 y]), 65% were female, 69% were Asian, and 49% had ≥2 prior lines. Confirmed ORR per IRC was 25%, with 1 CR; DCR was 76% [95% CI: 66–84]; median DOR was not reached (Table). In EXCLAIM, baseline brain metastases were present in 33/96 pts (34%); the first site of disease progression by IRC was the brain in 40% of all pts and 73% of pts with baseline brain metastases. Confirmed responses were seen in all prespecified subgroups in PPP and EXCLAIM. Efficacy by EGFR ex20ins mutation variant will be presented. Treatment-related adverse events (TRAEs; >20%) in PPP were diarrhea (91%), rash (45%), paronychia (38%), decreased appetite (35%), nausea (34%), dry skin (31%), vomiting (30%), increased blood creatinine (25%), stomatitis (24%), and pruritus (21%); the only grade ≥3 TRAE in ≥5% was diarrhea (22%). AEs leading to discontinuation in >2% were diarrhea (4%) and nausea (4%). A similar safety profile was observed in EXCLAIM. Conclusions: Mobocertinib demonstrated clinically meaningful benefit for pts with EGFR ex20ins+ mNSCLC in PPP and EXCLAIM cohorts, with a manageable safety profile. Clinical trial information: NCT02716116. [Table: see text]