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Research Article
Xichun Hu
Fudan University Shanghai Cancer Center
Corresponding Author
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Purpose: This is a phase Ia, first-in-human study aiming to assess the safety, maximum tolerated dose (MTD), pharmacokinetic (PK) and anti-tumor activity of FCN-437c, CDK4/6 inhibitor, as monotherapy in patients with HR+HER2- ABC (advanced breast cancer) who failed standard of care.
Methods: Regular 3+3 dose escalation design was utilized with starting dose of 50 mg per day for 3 weeks on -1 week off treatment in a 28-day cycle. Seventeen eligible female patients with HR+HER2- ABC were enrolled at different dose levels: 50 mg (n = 3), 100 mg (n = 3), 200 mg (n = 3), 300 mg (n = 6) and 450 mg (n = 2).
Results: Two patients in the 450 mg dose group experienced DLT of grade 4 thrombocytopenia and neutropenia respectively, and no DLT was observed in other dose levels. The most frequently reported TEAEs was hematological, including leukopenia (94.1%), neutropenia (88.2%), anemia (64.7%) and thrombocytopenia (47.1%). Major grade 3-4 TEAEs were neutropenia and leukopenia, occurring in 11 (64.7%) and 8 (47.1%) patients, respectively. The exposure increased almost in proportion to given dose ranging from 50 to 200 mg. At multiple dose levels from 200 to 450 mg, there appeared to be a trend of saturation. MTD was determined to be 300 mg. Of 15 measurable patients, nine (60.0%) had the best response of stable disease and no objective response was observed.
Conclusions: FCN-437c has established an acceptable safety profile with no unexpected signals compared to other CDK4/6 inhibitors. (NCT04488107, Jul 13th 2020)
Keywords
CDK4/6 inhibitor, FCN-437c, safety, pharmacokinetics, efficacy
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This preprint is under consideration at Investigational New Drugs. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Xichun Hu
Fudan University Shanghai Cancer Center
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 03 Mar, 2021
No community comments so far
Reviewers invited
Invitations sent on 25 Feb, 2021
Editor assigned
On 21 Feb, 2021
First submitted
On 19 Feb, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Purpose: This is a phase Ia, first-in-human study aiming to assess the safety, maximum tolerated dose (MTD), pharmacokinetic (PK) and anti-tumor activity of FCN-437c, CDK4/6 inhibitor, as monotherapy in patients with HR+HER2- ABC (advanced breast cancer) who failed standard of care.
Methods: Regular 3+3 dose escalation design was utilized with starting dose of 50 mg per day for 3 weeks on -1 week off treatment in a 28-day cycle. Seventeen eligible female patients with HR+HER2- ABC were enrolled at different dose levels: 50 mg (n = 3), 100 mg (n = 3), 200 mg (n = 3), 300 mg (n = 6) and 450 mg (n = 2).
Results: Two patients in the 450 mg dose group experienced DLT of grade 4 thrombocytopenia and neutropenia respectively, and no DLT was observed in other dose levels. The most frequently reported TEAEs was hematological, including leukopenia (94.1%), neutropenia (88.2%), anemia (64.7%) and thrombocytopenia (47.1%). Major grade 3-4 TEAEs were neutropenia and leukopenia, occurring in 11 (64.7%) and 8 (47.1%) patients, respectively. The exposure increased almost in proportion to given dose ranging from 50 to 200 mg. At multiple dose levels from 200 to 450 mg, there appeared to be a trend of saturation. MTD was determined to be 300 mg. Of 15 measurable patients, nine (60.0%) had the best response of stable disease and no objective response was observed.
Conclusions: FCN-437c has established an acceptable safety profile with no unexpected signals compared to other CDK4/6 inhibitors. (NCT04488107, Jul 13th 2020)
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