Treatment Outcomes and Safety of Mobocertinib in Platinum-Pretreated Patients With EGFR Exon 20 Insertion–Positive Metastatic Non–Small Cell Lung Cancer : A Phase 1/2 Open-label Nonrandomized Clinical Trial

Abstract

<p class="first" id="d1143030e518">This nonrandomized clinical trial evaluates the treatment outcomes and safety of mobocertinib treatment in patients with previously treated <i>EGFR</i> exon 20 insertion–positive metastatic non–small cell lung cancer. </p><div class="section"> <a class="named-anchor" id="ab-coi210069-1"> <!-- named anchor --> </a> <h5 class="section-title" id="d1143030e527">Question</h5> <p id="d1143030e529">Does mobocertinib have activity in patients with <i>EGFR </i>exon 20 insertion ( <i>EGFR</i>ex20ins)–positive metastatic non–small cell lung cancer (mNSCLC) previously treated with platinum-based chemotherapy? </p> </div><div class="section"> <a class="named-anchor" id="ab-coi210069-2"> <!-- named anchor --> </a> <h5 class="section-title" id="d1143030e538">Findings</h5> <p id="d1143030e540">In this nonrandomized clinical trial, mobocertinib showed antitumor activity in patients with platinum-pretreated <i>EGFR</i>ex20ins-positive mNSCLC, with a confirmed objective response rate of 28%, median duration of response of 17.5 months, and median progression-free survival of 7.3 months by independent review committee assessments. The safety profile was characterized by gastrointestinal and cutaneous adverse events, which were largely manageable. </p> </div><div class="section"> <a class="named-anchor" id="ab-coi210069-3"> <!-- named anchor --> </a> <h5 class="section-title" id="d1143030e546">Meaning</h5> <p id="d1143030e548">Mobocertinib has a favorable risk-benefit profile in patients with previously treated <i>EGFR</i>ex20ins-positive mNSCLC. </p> </div><div class="section"> <a class="named-anchor" id="ab-coi210069-4"> <!-- named anchor --> </a> <h5 class="section-title" id="d1143030e556">Importance</h5> <p id="d1143030e558">Metastatic non–small cell lung cancer (mNSCLC) with <i>EGFR</i> exon 20 insertion ( <i>EGFR</i>ex20ins) mutations is associated with a poor prognosis. Mobocertinib is an oral tyrosine kinase inhibitor designed to selectively target <i>EGFR</i>ex20ins mutations. </p> </div><div class="section"> <a class="named-anchor" id="ab-coi210069-5"> <!-- named anchor --> </a> <h5 class="section-title" id="d1143030e570">Objective</h5> <p id="d1143030e572">To evaluate treatment outcomes and safety of mobocertinib in patients with previously treated <i>EGFR</i>ex20ins-positive mNSCLC. </p> </div><div class="section"> <a class="named-anchor" id="ab-coi210069-6"> <!-- named anchor --> </a> <h5 class="section-title" id="d1143030e578">Design, Setting, and Participants</h5> <p id="d1143030e580">This 3-part, open-label, phase 1/2 nonrandomized clinical trial with dose-escalation/dose-expansion cohorts (28 sites in the US) and a single-arm extension cohort (EXCLAIM; 40 sites in Asia, Europe, and North America) was conducted between June 2016 and November 2020 (data cutoff date). The primary analysis populations were the platinum-pretreated patients (PPP) cohort and the EXCLAIM cohort. The PPP cohort included 114 patients with platinum-pretreated <i>EGFR</i>ex20ins-positive mNSCLC who received mobocertinib 160 mg once daily from the dose-escalation (n = 6), dose-expansion (n = 22), and EXCLAIM (n = 86) cohorts. The EXCLAIM cohort included 96 patients with previously treated <i>EGFR</i>ex20ins-positive mNSCLC (10 were not platinum pretreated and thus were excluded from the PPP cohort). </p> </div><div class="section"> <a class="named-anchor" id="ab-coi210069-7"> <!-- named anchor --> </a> <h5 class="section-title" id="d1143030e589">Interventions</h5> <p id="d1143030e591">Mobocertinib 160 mg once daily.</p> </div><div class="section"> <a class="named-anchor" id="ab-coi210069-8"> <!-- named anchor --> </a> <h5 class="section-title" id="d1143030e594">Main Outcomes and Measures</h5> <p id="d1143030e596">The primary end point of the PPP and EXCLAIM cohorts was confirmed objective response rate (ORR) assessed by independent review committee (IRC). Secondary end points included confirmed ORR by investigator, duration of response, progression-free survival, overall survival, and safety. </p> </div><div class="section"> <a class="named-anchor" id="ab-coi210069-9"> <!-- named anchor --> </a> <h5 class="section-title" id="d1143030e599">Results</h5> <p id="d1143030e601">Among the PPP (n = 114) and EXCLAIM (n = 96) cohorts, the median (range) age was 60 (27-84) and 59 (27-80) years, respectively; most patients were women (75 [66%] and 62 [65%], respectively) and of Asian race (68 [60%] and 66 [69%], respectively). At data cutoff, median follow-up was 14.2 months in the PPP cohort (median 2 prior anticancer regimens; 40 [35%] had baseline brain metastases), with confirmed ORR of 28% (95% CI, 20%-37%) by IRC assessment and 35% (95% CI, 26%-45%) by investigator assessment; median duration of response by IRC assessment was 17.5 months (95% CI, 7.4-20.3). Median progression-free survival by IRC assessment was 7.3 months (95% CI, 5.5-9.2). Median overall survival was 24.0 months (95% CI, 14.6-28.8). In the EXCLAIM cohort, median follow-up was 13.0 months, with confirmed ORR by IRC assessment of 25% (95% CI, 17%-35%) and by investigator assessment of 32% (95% CI, 23%-43%). The most common treatment-related adverse events were diarrhea and rash. </p> </div><div class="section"> <a class="named-anchor" id="ab-coi210069-10"> <!-- named anchor --> </a> <h5 class="section-title" id="d1143030e604">Conclusions and Relevance</h5> <p id="d1143030e606">In this open-label, phase 1/2 nonrandomized clinical trial, mobocertinib was associated with clinically meaningful benefit in patients with previously treated <i>EGFR</i>ex20ins-positive mNSCLC, with a manageable safety profile. </p> </div><div class="section"> <a class="named-anchor" id="ab-coi210069-11"> <!-- named anchor --> </a> <h5 class="section-title" id="d1143030e612">Trial Registration</h5> <p id="d1143030e614">ClinicalTrials.gov Identifier: <a data-untrusted="" href="https://clinicaltrials.gov/ct2/show/NCT02716116" id="d1143030e616" target="xrefwindow">NCT02716116</a> </p> </div>