Highlights from

ESMO 2019

European Society for Medical Oncology Congress 2019

Barcelona 27 September - 01 October 2019

Mixed data: AMG 510 in tumours with KRASG12C

The ongoing phase 1 study evaluating investigative drug AMG 510 in patients with previously treated KRAS G12C-mutant solid tumours (KRASG12C) was presented by Prof. Ramaswamy Govindan (Washington University, St Louis, USA) [1]. The data include the first evidence of anti-tumour activity reported in patients with colorectal cancer (CRC) and appendiceal cancer, as well as previously presented non-small cell lung cancer (NSCLC) findings. AMG 510 continues to be well-tolerated with no dose-limiting toxicities.

This first-in-human, open-label, multicentre study enrolled 76 patients with KRASG12C-mutant solid tumours. Eligible patients were heavily pre-treated with at least two prior lines of treatment. The primary endpoint was safety, and key secondary endpoints include pharmacokinetics, objective response rate (assessed every 6 weeks), duration of response, and progression-free survival. Patients were enrolled in 4 dose cohorts: 180 mg, 360 mg, 720 mg, and 960 mg, taken orally once daily.

A subset of 55 evaluable patients as of the July 2019 data cut-off were presented, including CRC, appendiceal cancer, and NSCLC patients. Of these, 29 had CRC, 12 of whom received the target dose of 960 mg once daily (see Figure). Only 1 patient in this dose cohort experienced a partial response, and 10 had stable disease for a disease control rate of 92%. Of the evaluable patients with NSCLC, 13 received 960 mg, of which 7 (54%) achieved a partial response at one or more timepoints and 6 (46%) achieved stable disease, for a disease control rate of 100%. Data across dosing cohorts also showed tumour responses in 2 evaluable patients with appendiceal cancer with 1 partial response and 1 experiencing stable disease.

Among the 76 patients enrolled across treatment groups, 52 remain on treatment. The majority of treatment-related adverse events (AEs) were grade 1 and 2. Only two treatment-related AEs were grade 3 (diarrhoea and anaemia). Thus, although the primary endpoint of safety was met, the single partial response in the CRC cohort was disappointing with regard to efficacy, despite better response in NSCLC.

Keywords: Carcinoma, Non-Small-Cell Lung; Appendiceal Neoplasms; Lung Neoplasms; Colorectal Neoplasms; AMG 510

Figure. Change in colorectal (CRC) tumour burden after treatment with AMG 510.

Figure. Change in colorectal (CRC) tumour burden after treatment with AMG 510

Figure provided by ESMO.

  1. Govindan R et al. ESMO Congress 2019. Abstract 446PD.

Top image: STEVE GSCHMEISSNER / SCIENCE PHOTO LIBRARY

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