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Jayesh Desai



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    OA01 - Precision Medicine and Personalized Therapy for Lung Cancer (ID 1)

    • Event: NACLC 2019
    • Type: Oral Abstract Session
    • Track:
    • Presentations: 1
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      OA01.06 - Safety, Efficacy, and Pharmacokinetics of AMG 510, a Novel KRASG12C Inhibitor, in Patients with Non-Small Cell Lung Cancer (ID 43)

      14:00 - 15:40  |  Author(s): Jayesh Desai

      • Abstract
      • Slides

      Background:
      KRASG12C mutation occurs in approximately 13-14% of non-small cell lung cancer (NSCLC). Currently, no approved therapy targets this mutation. AMG 510 is a novel small molecule that specifically and irreversibly inhibits KRASG12C by locking it in the inactive GDP-bound state.


      Method:
      This is a phase 1, first-in-human, open-label, multicenter study of AMG 510 in adult patients with advanced KRASG12C mutant solid tumors, including NSCLC, colorectal cancer, and other tumor types. Primary endpoint is safety; secondary endpoints include objective response rate, duration of response, disease control rate, progression-free survival, and pharmacokinetics. Key inclusion criteria: KRASG12C mutation identified through DNA sequencing; measurable disease; progression on standard therapy; and ECOG PS ? 2. Key exclusion criteria: active (untreated) brain metastases; myocardial infarction within 6 mo. Eligible patients were enrolled into 4 dose exploration cohorts with planned dose level of 180, 360, 720, and 960mg, respectively, administered orally once daily. After maximum tolerated dose (MTD) is identified, additional patients will be enrolled and treated at MTD in expansion cohort. Treatment continues until disease progression, intolerance, or consent withdrawal.


      Results:
      As of 4 April 2019, 14 patients (8 females) with NSCLC were enrolled into dose exploration cohorts. Median age was 65.5 years (range: 53–77). 13/14 (93%) patients were former or current smokers. All patients had > 2 prior lines of anticancer therapy and were previously treated with anti-PD1/L1 therapies. 12 patients remained on AMG 510 while 2 discontinued due to progressive disease (PD). Median treatment duration was 56 days (range: 9–192). No dose-limiting toxicities were observed. Six patients reported 10 treatment-related adverse events (TRAEs) (6 grade 1; 2 grade 2; and 2 grade 3). Grade 3 TRAEs were anemia and diarrhea occurring in 1 patient each. No grade 4 or serious AEs were reported. The most frequently reported AEs were decreased appetite and diarrhea observed in 4 (29%) and 3 (21%) patients, respectively. Tumor response was evaluable in 10 patients. Five patients (50%) (1 at 180mg, 1 at 360mg, 3 at 960mg) had a partial response (4 were confirmed), 4 patients (40%) (2 at 180mg, 2 at 720mg) had stable disease, and 1 patient (at 720mg) had PD. 8/10 evaluable patients had treatment ongoing. Updated data will be presented at the conference.


      Conclusion:
      AMG 510 is well tolerated at all 4 dose levels and shows antitumor activity when administered as monotherapy to patients with advanced KRASG12C mutant NSCLC. Enrollment is ongoing (ClinicalTrials.gov identifier, NCT03600883).

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