Abstract 1231P
Background
Mobocertinib, an oral EGFR tyrosine kinase inhibitor (TKI) designed to target EGFRex20ins mutations, demonstrated clinical efficacy in 114 platinum-pretreated EGFRex20ins+ NSCLC patients (PPP) in a phase I/II study (NCT02716116). Confirmed objective responses by independent assessment were reported in 28% of patients with median duration of response of 17.5 months. Skin toxicities are commonly reported with irreversible EGFR TKIs, including skin rash, dry skin, and paronychia.
Methods
All patients received 160 mg QD mobocertinib. We report type and incidence of any-grade (gr) and gr ≥3 skin toxicity treatment-emergent adverse events (TEAEs), frequency of dose modifications (reduction, discontinuation), and management of these events.
Results
Among 114 patients in the PPP cohort, skin toxicity events were observed in 105 (92%), with gr ≥3 events in 5 patients (4%). No patients had serious events, 5 (4%) dose reduced, and 1 patient (<1%) required dose discontinuation. Median time to onset was 9 days and median time to resolution of gr 2 and gr 3 events were 9 and 5 weeks, respectively. Rash, paronychia, dry skin, and pruritus were the most commonly reported skin toxicities (>20% of patients) (Table). Proactive management included skin care and use of topical corticosteroids (43%) including hydrocortisone (12%) and antibiotics (28%), such as clindamycin (21%) and mupirocin (18%). Table: 1231P
Skin toxicity TEAEs in >10% of patients
| Data cut-off: 01 November 2020 | Platinum-pretreated patients N=114 n (%) |
| Patients with ≥1 skin event | 105 (92) |
| Rash* | 97 (85) |
| Rash | 52 (46) |
| Pruritus | 29 (25) |
| Dermatitis acneiform | 22 (19) |
| Rash maculopapular | 16 (14) |
| Paronychia | 44 (39) |
| Dry skin | 41 (36) |
| Alopecia | 23 (20) |
*TEAEs grouped under Rash
Conclusions
The majority of skin toxicity events were low grade, started within the first 2 weeks of treatment, and were largely managed with skin care and proactive use of topical steroids and/or antibiotics. Types of skin toxicities observed with mobocertinib are consistent with those reported with the class of EGFR TKIs, with low frequency of high-grade toxicity.
Clinical trial identification
NCT02716116; Release date: 23 March 2006.
Editorial acknowledgement
Editorial assistance was provided by Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, USA, and funded by Millennium Pharmaceuticals, Inc.
Legal entity responsible for the study
Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Funding
Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Disclosure
J.C. Yang: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, GSK, Janssen, Merck Serono, MSD, Novartis, Ono Pharmaceuticals, Pfizer, Puma Pharmaceuticals, Roche/Genentech, Takeda Oncology, Yuhan Pharmaceuticals; Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Novartis; Financial Interests, Personal, Other, coordinating PI: AstraZeneca, Daiichi Sankyo, Dizal Pharmaceutical, MSD; Financial Interests, Personal, Other, Steering Committee: Bayer, Eli Lilly, Ipsen, Janssen, Merck, Novartis, Numab, Takeda Oncology. S.S. Ramalingam: Financial Interests, Personal, Other, Honoraria or Advisory Role: Amgen, AstraZeneca, Bristol Myers Squibb, Merck, Lilly, Genentech/Roche, GlaxoSmithKline, Takeda; Financial Interests, Institutional, Other, Research Support: Amgen, Advaxis, BMS, Genmab, AstraZeneca, Takeda. T.M. Kim: Financial Interests, Personal, Other, Honoraria or advisory role: AstraZeneca, Boryung, F. Hoffmann-La Roche Ltd./Genentech Inc., Novartis, Sanofi, Takeda; Financial Interests, Personal, Other, Research funding: AstraZeneca-Korea Health Industry Development Institute. G.J. Riely: Financial Interests, Personal, Other, Travel: Merck, Sharp & Dohme; Financial Interests, Institutional, Other, Research funding: Novartis, Roche/Genentech, Millennium, GSK, Pfizer, Infinity Pharmaceuticals, ARIAD, Mirati Therapeutics, Merck. T. Mekhail: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, BMS, Lilly, Merck, Takeda; Financial Interests, Personal, Advisory Board: AstraZeneca, Lilly. M.R. Garcia Campelo: Financial Interests, Personal, Other, Consulting/advisory role: Takeda, AstraZeneca, Roche, Pfizer, BMS, Boehringer Ingelheim, Pfizer, Janssen, Eli Lilly, MSD, Sanofi. E. Felip: Financial Interests, Personal, Other, Consulting/advisory role: AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Eli Lilly, Guardant Health, MSD, Novartis, Pfizer, Roche, Takeda, Merck. L. Bazhenova: Financial Interests, Personal, Other, Stock and other ownership interests: Epic Sciences; Financial Interests, Personal, Other, consulting or advisory role: Neuvogen, Janssen, Daiichi Sankyo, Boehringer Ingelheim, Merck, Regeneron, Bristol Myers Squibb, Novartis; Financial Interests, Personal, Other, research funding: BeyondSpring. S. Jin: Financial Interests, Personal, Full or part-time Employment: Takeda. C. Griffin: Financial Interests, Personal, Full or part-time Employment: Takeda. V. Bunn: Financial Interests, Personal, Full or part-time Employment: Takeda. J. Lin: Financial Interests, Personal, Full or part-time Employment: Takeda. E.N. Churchill: Financial Interests, Personal, Full or part-time Employment: Takeda. M. Mehta: Financial Interests, Personal, Full or part-time Employment: Takeda. P.A. Janne: Financial Interests, Personal, Other, Consulting: Araxes Pharmaceuticals, ARIAD/Takeda, AstraZeneca, Boehringer Ingelheim, Chugai, Ignyta, Lilly, Loxo Oncology, Merrimack, Mirati Therapeutics, Pfizer, Roche, Novartis, Voronoi, Daiichi Sankyo, SFJ Pharmaceuticals, Biocartis; Financial Interests, Personal, Other, research support: Astellas, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Lilly, Puma Biotechnology; Financial Interests, Personal, Stocks/Shares: Gatekeeper and Loxo Oncology; Financial Interests, Personal, Royalties: Dana-Farber Cancer Institute-owned patent on EGFR mutations licensed to LabCorp. C. Zhou: Financial Interests, Personal, Other, Honoraria or advisory role: Lilly China, Sanofi, BI, Roche, MSD, Qilu, Hengrui, Innovent Biologics, C-Stone, LUYE Pharma, TopAlliance Biosciences Inc., Amoy Diagnostics. All other authors have declared no conflicts of interest.