988P Phase I/II study of mobocertinib in EGFR exon 20 insertion (ex20ins) + metastatic NSCLC (mNSCLC): Updated results from platinum-pretreated patients (PPP)

Mobocertinib (TAK-788) is an oral tyrosine kinase inhibitor selectively targeting epidermal growth factor receptor gene (EGFR) ex20ins+ non–small cell lung cancer (NSCLC). In a Phase 1/2 trial, mobocertinib demonstrated clinical activity in PPP with EGFR ex20ins+ mNSCLC (Nov 1, 2020 data cutoff; Zhou, JAMA Oncol. 2021;7(12):e214761). This 3-part, open-label study (NCT02716116) consisted of dose-escalation and dose-expansion cohorts, as well as an extension cohort (EXCLAIM). Patients with EGFR ex20ins+ mNSCLC, Eastern Cooperative Oncology Group 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 (cORR; RECIST v1.1) per independent review committee (IRC). We present updated efficacy and safety data for the PPP cohort. Results are from Nov 1, 2021 (data cutoff), ∼24 mo after last patient enrollment (median follow-up: 25.8 mo). In the PPP cohort (n=114), median age was 60 years (range: 27–84 years), 66% of patients were female, 60% were Asian, and 59% had received ≥2 prior systemic anticancer lines. The cORR was 28.1%, median duration of response was 15.8 mo, and median progression-free survival was 7.3 mo (all per IRC; Table). Confirmed responses were observed in all prespecified subgroups. The most common treatment-related adverse events (TRAEs) were diarrhea (92%), rash (46%), paronychia (38%), decreased appetite (37%), nausea (34%), vomiting (32%), and dry skin (31%). The only Grade ≥3 TRAE observed in ≥10% of patients was diarrhea (23%). The only AE leading to discontinuation in >2% of patients was diarrhea (4%).Table: 988PPPP Cohort (n=114)Median follow-up [95% CI], mo25.8 [24.6–26.7]Confirmed ORR, n (%) [95% CI] Per IRC Per INV32 (28) [20–37] 40 (35) [26–45]DCR, n (%) [95% CI] Per IRC Per INV89 (78) [69–85] 89 (78) [69–85]Median DORa, mo [95% CI] Per IRC Per INV15.8 [7.4–19.4] 13.9 [5.6–19.4]Median PFSa, mo [95% CI] Per IRC Per INV7.3 [5.5–9.2] 7.3 [5.6–8.8]Median OSa, mo [95% CI] 12-mo ratea, % 18-mo ratea, %20.2 [14.9–25.3] 70 55DCR, disease control rate; DOR, duration of response; INV, investigator; OS, overall survival; PFS, progression-free survival. a Per Kaplan-Meier method. Open table in a new tab DCR, disease control rate; DOR, duration of response; INV, investigator; OS, overall survival; PFS, progression-free survival. a Per Kaplan-Meier method. At more than 2 years of follow-up in the Phase 1/2 trial, mobocertinib continues to demonstrate clinically meaningful benefit for PPP with EGFR ex20ins+ mNSCLC, with a manageable safety profile.