IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-34782-9.html
   My bibliography  Save this article

First-in-human phase Ia study of the PI3Kα inhibitor CYH33 in patients with solid tumors

Author

Listed:
  • Xiao-Li Wei

    (Sun Yat-sen University Cancer Center, Sun Yat-sen University)

  • Fu-Rong Liu

    (Sun Yat-sen University Cancer Center, Sun Yat-sen University)

  • Ji-Hong Liu

    (Sun Yat-sen University Cancer Center, Sun Yat-sen University)

  • Hong-Yun Zhao

    (Sun Yat-sen University Cancer Center, Sun Yat-sen University)

  • Yang Zhang

    (Sun Yat-sen University Cancer Center, Sun Yat-sen University)

  • Zhi-Qiang Wang

    (Sun Yat-sen University Cancer Center, Sun Yat-sen University)

  • Miao-Zhen Qiu

    (Sun Yat-sen University Cancer Center, Sun Yat-sen University)

  • Fei Xu

    (Sun Yat-sen University Cancer Center, Sun Yat-sen University)

  • Qiu-Qiong Yu

    (Haihe Biopharma Co., Ltd)

  • Yi-Wu Du

    (Haihe Biopharma Co., Ltd)

  • Yan-Xia Shi

    (Sun Yat-sen University Cancer Center, Sun Yat-sen University)

  • De-Sheng Wang

    (Sun Yat-sen University Cancer Center, Sun Yat-sen University)

  • Feng-Hua Wang

    (Sun Yat-sen University Cancer Center, Sun Yat-sen University)

  • Rui-Hua Xu

    (Sun Yat-sen University Cancer Center, Sun Yat-sen University
    Chinese Academy of Medical Sciences)

Abstract

PIK3CA mutations are highly prevalent in solid tumors. Targeting phosphatidylinositol 3-kinase α is therefore an attractive strategy for treating cancers harboring PIK3CA mutations. Here, we report the results from a phase Ia, open label, dose-escalation and -expansion study (NCT03544905) of CYH33, a highly selective PI3Kα inhibitor, in advanced solid tumors. The primary outcomes were the safety, tolerability, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of CYH33. The secondary outcomes included evaluation of pharmacokinetics, preliminary efficacy and changes in pharmacodynamic biomarkers in response to CYH33 treatment. The exploratory outcome was the relationship between the efficacy of CYH33 treatment and tumor biomarker status, including PIK3CA mutations. A total of 51 patients (19 in the dose escalation stage and 32 in the dose expansion stage) including 36 (70.6%) patients (4 in the dose escalation stage and 32 in the dose expansion stage) with PIK3CA mutations received CYH33 1–60 mg. The MTD of CYH33 was 40 mg once daily, which was also selected as the RP2D. The most common grade 3/4 treatment-related adverse events were hyperglycemia, rash, platelet count decreased, peripheral edema, and fatigue. Forty-two out of 51 patients were evaluable for response, the confirmed objective response rate was 11.9% (5/42). Among 36 patients harboring PIK3CA mutations, 28 patients were evaluable for response, the confirmed objective response rate was 14.3% (4/28). In conclusion, CYH33 exhibits a manageable safety profile and preliminary anti-tumor efficacy in solid tumors harboring PIK3CA mutations.

Suggested Citation

  • Xiao-Li Wei & Fu-Rong Liu & Ji-Hong Liu & Hong-Yun Zhao & Yang Zhang & Zhi-Qiang Wang & Miao-Zhen Qiu & Fei Xu & Qiu-Qiong Yu & Yi-Wu Du & Yan-Xia Shi & De-Sheng Wang & Feng-Hua Wang & Rui-Hua Xu, 2022. "First-in-human phase Ia study of the PI3Kα inhibitor CYH33 in patients with solid tumors," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34782-9
    DOI: 10.1038/s41467-022-34782-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-34782-9
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-34782-9?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Benjamin D. Hopkins & Chantal Pauli & Xing Du & Diana G. Wang & Xiang Li & David Wu & Solomon C. Amadiume & Marcus D. Goncalves & Cindy Hodakoski & Mark R. Lundquist & Rohan Bareja & Yan Ma & Emily M., 2018. "Publisher Correction: Suppression of insulin feedback enhances the efficacy of PI3K inhibitors," Nature, Nature, vol. 563(7731), pages 24-24, November.
    2. Benjamin D. Hopkins & Chantal Pauli & Xing Du & Diana G. Wang & Xiang Li & David Wu & Solomon C. Amadiume & Marcus D. Goncalves & Cindy Hodakoski & Mark R. Lundquist & Rohan Bareja & Yan Ma & Emily M., 2018. "Suppression of insulin feedback enhances the efficacy of PI3K inhibitors," Nature, Nature, vol. 560(7719), pages 499-503, August.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Ziwei Dai & Weiyan Zheng & Jason W. Locasale, 2022. "Amino acid variability, tradeoffs and optimality in human diet," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Nishanth Ulhas Nair & Patricia Greninger & Xiaohu Zhang & Adam A. Friedman & Arnaud Amzallag & Eliane Cortez & Avinash Das Sahu & Joo Sang Lee & Anahita Dastur & Regina K. Egan & Ellen Murchie & Miche, 2023. "A landscape of response to drug combinations in non-small cell lung cancer," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Meredith L. Jenkins & Harish Ranga-Prasad & Matthew A. H. Parson & Noah J. Harris & Manoj K. Rathinaswamy & John E. Burke, 2023. "Oncogenic mutations of PIK3CA lead to increased membrane recruitment driven by reorientation of the ABD, p85 and C-terminus," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Miyuki Nomura & Mai Ohuchi & Yoshimi Sakamoto & Kei Kudo & Keisuke Yaku & Tomoyoshi Soga & Yuki Sugiura & Mami Morita & Kayoko Hayashi & Shuko Miyahara & Taku Sato & Yoji Yamashita & Shigemi Ito & Nao, 2023. "Niacin restriction with NAMPT-inhibition is synthetic lethal to neuroendocrine carcinoma," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34782-9. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.