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ePoster Display

1246P - A phase I dose-escalation study of mobocertinib (TAK-788), an oral tyrosine kinase inhibitor (TKI), in Japanese NSCLC patients

Date

16 Sep 2021

Session

ePoster Display

Presenters

Toyoaki Hida

Citation

Annals of Oncology (2021) 32 (suppl_5): S949-S1039. 10.1016/annonc/annonc729

Authors

T. Hida1, M. Nishino2, K. Yoh3, T. Asato4, T. Kitagawa5, S. Zhang6, M. Mehta7, Y. Ohe8

Author affiliations

  • 1 Department Of Thoracic Oncology, Aichi Cancer Center, 464-8681 - Aichi/JP
  • 2 Department Of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 135-8550 - Tokyo/JP
  • 3 Department Of Thoracic Oncology, National Cancer Center Hospital East, 277-8577 - Chiba/JP
  • 4 Oncology Clinical Research Department, Takeda Pharmaceutical Company Limited, 540-8645 - Osaka/JP
  • 5 Biostatistics, Japan Development Center, Takeda Pharmaceutical Company Limited, 540-8645 - Osaka/JP
  • 6 Quantitative Clinical Pharmacology, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, 02139 - Cambridge/US
  • 7 Clinical Science, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, 02139 - Cambridge/US
  • 8 Department Of Thoracic Oncology, National Cancer Center Hospital, 104-0045 - Tokyo/JP
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Abstract 1246P

Background

Mobocertinib is an orally administered TKI that potently inhibits activating epidermal growth factor receptor (EGFR) mutations, including in-frame insertions in exon 20, which are associated with poor survival. We present results from the phase I open-label, dose-escalation of a phase I/II study (NCT03807778), aimed to confirm the recommended phase II dose (RP2D)/maximum tolerated dose (MTD) identified in global studies (160 mg once daily [QD]) in Japanese patients with NSCLC.

Methods

Patients with histologically or cytologically confirmed locally advanced or metastatic NSCLC refractory to standard available therapies were included. Dose-escalation cohorts started with 40 mg QD followed by higher doses according to a Bayesian logistic regression model [MC1] until an MTD was found or 160 mg QD was shown to be safe and tolerable. MTD was reached when ≥9 patients at all doses were dose-limiting toxicity (DLT)-evaluable, ≥6 patients at the current dose level were DLT-evaluable, and the next recommended dose was equal to the current dose.

Results

In total, 20 patients (40 mg QD, n=4; 120 mg QD, n=4; 160 mg QD, n=12) were enrolled at 4 sites: 18 (90%) had tumors harboring EGFR exon 20 insertion mutation; all patients had ≥1 prior anticancer therapy, and 55% had received ≥3 regimens. No DLT was observed at 40 mg QD. One patient receiving 120 mg QD reported a DLT of diarrhea (Grade 3), and 2 patients receiving 160 mg QD reported DLT: one had interstitial lung disease (Grade 3), the other had aspartate aminotransferase increased (Grade 2), alanine aminotransferase increased (Grade 3) and diarrhea (Grade 2). All patients in the 160 mg QD cohort reported a treatment-emergent adverse event (TEAE). The most common TEAEs were diarrhea (reported in all but 1 patient receiving 40 mg QD) and nausea (50% of each dose cohort). MTD/RP2D of mobocertinib was confirmed as 160 mg QD. Pharmacokinetic parameters were also assessed and will be presented.

Conclusions

Mobocertinib showed a manageable safety profile in Japanese NSCLC patients. Based on the totality of pharmacokinetics and safety data from various mobocertinib doses, 160 mg QD was selected as the RP2D for further clinical studies in Japanese patients.

Clinical trial identification

TAK-788-1003.

Editorial acknowledgement

Hennis Tung - MIMS, Hong Kong, Ltd.

Legal entity responsible for the study

Takeda Pharmaceutical Company Limited.

Funding

Takeda Pharmaceutical Company Limited.

Disclosure

T. Hida: Financial Interests, Institutional, Principal Investigator: Takeda Pharmaceutical Company Limited; Financial Interests, Institutional, Principal Investigator: Janssen Pharmaceutical K.K.; Financial Interests, Institutional, Principal Investigator: AstraZeneca K.K.; Financial Interests, Institutional, Principal Investigator: Chugai Pharmaceutical Co., Ltd.; Financial Interests, Institutional, Principal Investigator: Nippon Boehringer Ingelheim Co., Ltd.; Financial Interests, Institutional, Principal Investigator: Novartis Pharma K.K. M. Nishino: Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb K.K.; Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceutical Co., Ltd.; Financial Interests, Personal, Speaker’s Bureau: Pfizer Japan Inc.; Financial Interests, Personal, Speaker’s Bureau: Chugai Pharmaceutical Co., Ltd.; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly Japan K.K.; Financial Interests, Personal, Speaker’s Bureau: Taiho Pharmaceutical Co., Ltd.; Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim Japan, Inc.; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca K.K.; Financial Interests, Personal, Speaker’s Bureau: MSD K.K.; Financial Interests, Personal, Speaker’s Bureau: Novartis Pharma K.K.; Financial Interests, Personal, Speaker’s Bureau: Daiichi Sankyo Healthcare Co., Ltd.; Financial Interests, Personal, Speaker’s Bureau: Merck Biopharma Co., Ltd. K. Yoh: Financial Interests, Personal, Invited Speaker: AstraZeneca K.K.; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb K.K.; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd.; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo Healthcare Co., Ltd.; Financial Interests, Personal, Invited Speaker: Janssen Pharmaceutical K.K.; Financial Interests, Personal, Invited Speaker: Eli Lilly Japan K.K.; Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical Co., Ltd.; Financial Interests, Personal, Invited Speaker: Novartis Pharma K.K.; Financial Interests, Personal, Invited Speaker: Kyowa Kirin Co., Ltd.; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim Japan, Inc.; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca K.K.; Financial Interests, Personal and Institutional, Research Grant: Eli Lilly Japan K.K.; Financial Interests, Personal and Institutional, Research Grant: Pfizer Japan Inc.; Financial Interests, Personal and Institutional, Research Grant: Daiichi Sankyo Healthcare Co., Ltd.; Financial Interests, Personal and Institutional, Research Grant: AbbVie GK; Financial Interests, Personal and Institutional, Research Grant: Taiho Pharmaceutical Co., Ltd.; Financial Interests, Personal and Institutional, Research Grant: Bayer Yakuhin, Ltd.; Financial Interests, Personal and Institutional, Research Grant: Takeda Pharmaceutical Company Limited; Financial Interests, Personal and Institutional, Research Grant: MSD K.K. T. Asato: Financial Interests, Personal and Institutional, Full or part-time Employment: Takeda Pharmaceutical Company Limited. T. Kitagawa: Financial Interests, Personal and Institutional, Full or part-time Employment: Takeda Pharmaceutical Company Limited. S. Zhang: Financial Interests, Personal, Full or part-time Employment: Takeda Pharmaceuticals. M. Mehta: Financial Interests, Personal, Full or part-time Employment: Takeda Pharmaceuticals. Y. Ohe: Financial Interests, Personal, Advisory Board: Takeda Pharmaceutical Company Limited; Financial Interests, Personal, Research Grant: Takeda Pharmaceutical Company Limited; Financial Interests, Personal, Invited Speaker: Takeda Pharmaceutical Company Limited.

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