1261MO - Updated results from a phase I/II study of mobocertinib (TAK-788) in NSCLC with EGFR exon 20 insertions (exon20ins)

Background

EGFR exon20ins occur in ∼1%‒2% of patients (pts) with NSCLC. Currently approved EGFR TKIs have not shown efficacy in most of these mutations. Mobocertinib is an investigational oral EGFR/HER2 inhibitor under evaluation in pts with metastatic NSCLC with EGFR exon20ins. We previously reported dose escalation and establishment of 160 mg qd as RP2D. We report updated antitumor activity and safety results from an open-label, multicenter study of mobocertinib (NCT02716116).

Methods

Antitumor activity by investigator-assessed radiographic response (RECIST 1.1) and toxicity (NCI CTCAE) were determined for pts with advanced, previously treated NSCLC with EGFR exon20ins who received mobocertinib 160 mg qd. Safety data were collected for all pts treated at 160 mg qd.

Results

As of 27 Jan 2020, 28 pts with previously treated NSCLC and EGFR exon20ins were treated in dose escalation/expansion at 160 mg qd. In these pts: median age, 62 y (range 28‒ 84); women, 75%; ECOG 0/1, 21%/79%; ≥2 prior anticancer therapies, 86%; brain metastases, 43%. Median time on treatment was 12 mo (13 treatment cycles) and 7 pts remain on treatment. Confirmed ORR (PR) was 43% (12/28; 95% CI 24‒63). The disease control rate was 86% (24/28; 95% CI 67–96). Two pts had best response of PD; 2 pts were not evaluable. Median duration of response in the 12 pts with confirmed PR was 14 mo (95% CI 5–not reached). The median PFS was 7.3 mo (95% CI 4.4‒15.6); 12-mo PFS was 33% (15‒52). Response to mobocertinib was observed in diverse EGFR exon20ins variants. Among these 28 pts, most common any grade treatment-related AEs (TRAEs; >25%) as assessed by investigator: diarrhea (82%), rash (46%), nausea (39%), decreased appetite (39%), vomiting (36%), paronychia (29%); grade ≥3 TRAEs (≥5%): diarrhea (32%), nausea (11%), increased lipase (7%), increased amylase (7%), stomatitis (7%), vomiting (7%). In all 136 pts treated with ≥1 dose of 160 mg, most common TRAEs: diarrhea (83%), nausea (43%), rash (33%), vomiting (27%); grade ≥3 TRAEs: diarrhea (21%) and increased lipase (5%).

Conclusions

Mobocertinib demonstrated antitumor activity in pts with advanced NSCLC with EGFR exon20ins. The safety profile for mobocertinib was consistent with other EGFR TKIs.

Clinical trial identification

NCT02716116 Release date: March 23, 2016.

Editorial acknowledgement

Professional medical writing assistance was provided by Lauren Gallagher, RPh, PhD, of Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, and funded by Millennium Pharmaceuticals, Inc., Cambridge, MA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

Legal entity responsible for the study

Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

Funding

Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

Disclosure

G.J. Riely: Travel/Accommodation/Expenses: Merck, Sharp & Dohme; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Roche/Genentech; Research grant/Funding (institution): Millennium; Research grant/Funding (institution): GSK; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Infinity Pharmaceuticals; Research grant/Funding (institution): ARIAD; Research grant/Funding (institution): Mirati Therapeutics; Research grant/Funding (institution): Merck. J.W. Neal: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy, Research grant/Funding (institution): Exelixis; Advisory/Consultancy: Jounce Therapeutics; Advisory/Consultancy, Research grant/Funding (institution): Takeda; Advisory/Consultancy: Lilly; Honoraria (self): Calithera Biosciences; Honoraria (self): Research to Practice; Honoraria (self): MLI Peerview; Honoraria (self): Medscape; Honoraria (self): Biomedical Learning Institute; Honoraria (self): Prime Oncology; Honoraria (self): Rockpointe; Honoraria (self): CME Matters; Honoraria (self): MJH CME; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (self): Nektar; Research grant/Funding (institution): Adaptimmune; Research grant/Funding (institution): GSK. D.R. Camidge: Honoraria (self): AstraZeneca; Honoraria (self): Takeda; Honoraria (self): Arrys/Kyn; Honoraria (self): Genoptix; Honoraria (self): GI Therapeutics (DSMB); Honoraria (self): Mersana Therapeutics; Honoraria (self): Roche/Genentech; Honoraria (self): Ignyta; Honoraria (self): Daiichi Sankyo (ILD adjudication committee); Honoraria (self): Hansoh SRC; Honoraria (self): Bio-Thera DSMB; Honoraria (self): Lycera; Honoraria (self): Revolution Med; Honoraria (self): Orion; Honoraria (self): Clovis; Honoraria (self): Celgene; Honoraria (self): Novartis; Research grant/Funding (self): ARIAD/Takeda. A. Spira: Advisory/Consultancy: ARIAD; Honoraria (self): AstraZeneca; Honoraria (self): Clovis Oncology; Honoraria (self), Speaker Bureau/Expert testimony: Roche. Z. Piotrowska: Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: ARIAD; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Takeda; Advisory/Consultancy: AbbVie; Advisory/Consultancy, Research grant/Funding (self): Novartis; Advisory/Consultancy, Research grant/Funding (self): Guardant Health; Advisory/Consultancy, Research grant/Funding (self): Spectrum; Advisory/Consultancy: ImmunoGen. L. Horn: Advisory/Consultancy: Merck; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Xcovery; Advisory/Consultancy: Genentech; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Incyte; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Tesaro; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Amgen; Advisory/Consultancy: Bayer; Travel/Accommodation/Expenses: BMS; Research grant/Funding (institution): Boehringer Ingelheim. D.B. Costa: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Takeda/Millennium Pharmaceuticals; Honoraria (self), Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Merrimack; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Clovis Oncology; Research grant/Funding (institution): Spectrum. A. Tsao: Advisory/Consultancy: Novartis; Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy, Research grant/Funding (institution): MedImmune; Advisory/Consultancy: Imedex; Advisory/Consultancy: Lilly; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): BMS; Advisory/Consultancy: Epizyme; Advisory/Consultancy: AstraZeneca/MedImmune; Advisory/Consultancy: ARIAD; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Takeda; Advisory/Consultancy: HERON; Licensing/Royalties: UptoDate; Research grant/Funding (self): Seattle Genetics; Research grant/Funding (self): Millennium; Research grant/Funding (self): Polaris; Research grant/Funding (institution): Merck. J. Patel: Advisory/Consultancy: AbbVie; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Takeda. S. Gadgeel: Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech/Roche; Advisory/Consultancy: ARIAD; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy: BMS; Advisory/Consultancy: AbbVie; Research grant/Funding (institution), Travel/Accommodation/Expenses: ARIAD/Takeda; Research grant/Funding (self), Research grant/Funding (institution): Merck; Research grant/Funding (institution): Blueprint Medicines. L. Bazhenova: Advisory/Consultancy: Genentech; Advisory/Consultancy, Research grant/Funding (self): BeyondSpring Pharmaceuticals; Advisory/Consultancy: GI Therapeutics; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: BI; Advisory/Consultancy: Takeda; Advisory/Consultancy: Blueprint; Shareholder/Stockholder/Stock options: Epic Sciences. V.W. Zhu: Honoraria (self), Speaker Bureau/Expert testimony: AstraZeneca; Honoraria (self), Speaker Bureau/Expert testimony: Roche-Foundation Medicine; Honoraria (self), Speaker Bureau/Expert testimony: Roche/Genentech; Honoraria (self), Speaker Bureau/Expert testimony: Takeda; Advisory/Consultancy, Shareholder/Stockholder/Stock options: TP Therapeutics. H. West: Advisory/Consultancy, Speaker Bureau/Expert testimony: Genentech/Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda/ARIAD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer. R. Gentzler: Honoraria (self): Rockpointe CME; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Jounce; Research grant/Funding (institution): Helsinn. V. Bunn: Full/Part-time employment: Takeda. S. Jin: Full/Part-time employment: Takeda. Z. Feng: Full/Part-time employment: Takeda. P.A. Jänne: Advisory/Consultancy: Araxes Pharmaceuticals; Advisory/Consultancy: ARIAD/Takeda; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): Boehringer Ingelheim; Advisory/Consultancy: Chugai; Advisory/Consultancy: Ignyta; Advisory/Consultancy, Research grant/Funding (self): Lilly; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Loxo Oncology; Advisory/Consultancy: Merrimack; Advisory/Consultancy: Mirati Therapeutics; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Roche; Advisory/Consultancy: Novartis; Advisory/Consultancy: Voronoi; Advisory/Consultancy, Research grant/Funding (self): Daiichi Sankyo; Advisory/Consultancy: SFJ Pharmaceuticals; Advisory/Consultancy: Biocartis; Research grant/Funding (self): Astellas; Research grant/Funding (self): Puma Biotechnology; Shareholder/Stockholder/Stock options: Gatekeeper; Licensing/Royalties, patent on EGFR mutations licensed to LabCorp: Dana-Farber Cancer Institute. All other authors have declared no conflicts of interest.