Suresh S. Ramalingam, MD, FASCO, Deputy Director, lead of the integration of the research, clinical, and educational components within Winship Cancer Institute of Emory University speaks about ASCO 2021 – Abstract – Mobocertinib (TAK-788) in EGFR exon 20 insertion (ex20ins)+ metastatic NSCLC (mNSCLC): Additional results from platinum-pretreated patients (pts) and EXCLAIM cohort of phase 1/2 study.
Link to Abstract:
https://meetinglibrary.asco.org/record/198352/abstract
Background information:
There are no authorized targeted treatments for EGFR ex20ins+ mNSCLC. Mobocertinib, a first-in-class, powerful oral TKI that targets EGFR ex20ins mutations, has received Breakthrough Therapy Designation in the United States and China for patients with EGFR ex20ins+ mNSCLC after platinum-based treatment.
Methodologies:
Dose-escalation/expansion and extension (EXCLAIM) groups are included in this three-part, open-label, multicenter trial (NCT02716116). Mobocertinib 160 mg QD was given to patients with EGFR ex20ins+ mNSCLC, ECOG level 0–1, and 1 previous line of treatment for locally advanced/metastatic illness. The primary outcome was the independent review committee’s assessment of the confirmed objective response rate (ORR; RECIST v1.1) (IRC). Additional effectiveness and safety data for 114 platinum-pretreated patients (PPP) and 96 EXCLAIM safety cohort patients are presented.
The following are the outcomes:
The data cutoff date is November 1, 2020, and the results are from that date. PPP participants (n=114; median age 60 years [27–84 years]) were 66% female, 60% Asian, and 59 percent had received at least two previous systemic anticancer lines. The confirmed ORR per IRC was 28%, with one complete response (CR); the disease control rate (DCR) was 78 percent [95% CI: 69–85]; and the median duration of response (DOR) was 17.5 months (Table). 65 percent of the participants in EXCLAIM (n=96; median age 59 years [27–80 years]) were female, 69 percent were Asian, and 49 percent had two or more previous lines. The confirmed ORR per IRC was 25%, with 1 CR; the DCR was 76 percent [95 percent CI: 66–84]; and the median DOR was not met (Table). In EXCLAIM, baseline brain metastases were present in 33/96 patients (34%); in IRC, the brain was the primary site of disease progression in 40% of all patients and 73% of those with baseline brain metastases. In PPP and EXCLAIM, confirmed answers were observed in all prespecified categories. The effectiveness of the EGFR ex20ins mutant variation will be discussed. Diarrhea (91 percent), rash (45 percent), paronychia (38 percent), decreased appetite (35 percent), nausea (34 percent), dry skin (31 percent), vomiting (30 percent), increased blood creatinine (25 percent), stomatitis (24 percent), and pruritus (21 percent) were the most common treatment-related adverse events (TRAEs) in PPP; the only grade 3 TRAE was diarrhea (5%). (22 percent ). Diarrhea (4 percent) and nausea (2 percent) were the most common AEs that caused people to stop taking the drug (4 percent ). In EXCLAIM, a similar safety profile was seen.
Final Thoughts:
In the PPP and EXCLAIM trials, mobocertinib showed clinically substantial benefit in patients with EGFR ex20ins+ mNSCLC, with a tolerable safety profile.
NCT02716116 is the number for the clinical trial.