Ethnic sensitivity assessment: Polatuzumab vedotin pharmacokinetics in Asian and non‐Asian patients with previously untreated diffuse large B‐cell lymphoma in POLARIX
Abstract This ethnic sensitivity analysis used data from the phase III POLARIX study (NCT03274492) to assess polatuzumab vedotin pharmacokinetics (PKs) in Asian versus non‐Asian patients with previously untreated diffuse large B‐cell lymphoma and examined the appropriateness of extrapolating global...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-12-01
|
| Series: | Clinical and Translational Science |
| Online Access: | https://doi.org/10.1111/cts.13669 |
| _version_ | 1797391728845520896 |
|---|---|
| author | Michael Z. Liao Rong Deng Leonid Gibiansky Tong Lu Priya Agarwal Randall Dere Calvin Lee Jamie Hirata Charles Herbaux Gilles Salles Chunze Li Dale Miles |
| author_facet | Michael Z. Liao Rong Deng Leonid Gibiansky Tong Lu Priya Agarwal Randall Dere Calvin Lee Jamie Hirata Charles Herbaux Gilles Salles Chunze Li Dale Miles |
| author_sort | Michael Z. Liao |
| collection | DOAJ |
| description | Abstract This ethnic sensitivity analysis used data from the phase III POLARIX study (NCT03274492) to assess polatuzumab vedotin pharmacokinetics (PKs) in Asian versus non‐Asian patients with previously untreated diffuse large B‐cell lymphoma and examined the appropriateness of extrapolating global study findings to Asian patients. PK and population PK (PopPK) analyses assessed polatuzumab vedotin analyte exposures by ethnicity (Asian [n = 84] vs. non‐Asian [n = 345] patients) and region (patients enrolled from Asia [n = 80] vs. outside Asia [n = 349]). In patients from Asia versus outside Asia, observed mean antibody‐conjugated monomethyl auristatin E (acMMAE) concentrations were comparable (1.2% lower at cycle [C]1 postdose, 4.4% higher at C4 predose; and 6.8% lower at C4 postdose in patients from Asia). Observed mean unconjugated MMAE was lower in patients from Asia by 6.5% (C1 postdose), 20.0% (C4 predose), and 15.3% (C4 postdose). In the PopPK analysis, C6 area under the curve and peak plasma concentrations were also comparable for acMMAE (6.3% and 3.0% lower in Asian vs. non‐Asian patients, respectively) and lower for unconjugated MMAE by 19.1% and 16.7%, respectively. By region, C6 mean acMMAE concentrations were similar, and C6 mean unconjugated MMAE concentrations were lower, in patients enrolled from Asia versus outside Asia, by 3.9%–7.0% and 17.3%–19.7%, respectively. In conclusion, polatuzumab vedotin PKs were similar between Asian and non‐Asian patients by ethnicity and region, suggesting PKs are not sensitive to Asian ethnicity and dose adjustments are not required in Asian patients to maintain efficacy and safety. |
| first_indexed | 2024-03-08T23:36:52Z |
| format | Article |
| id | doaj.art-8694ec4d77c146a69f093aef77194270 |
| institution | Directory Open Access Journal |
| issn | 1752-8054 1752-8062 |
| language | English |
| last_indexed | 2024-03-08T23:36:52Z |
| publishDate | 2023-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Science |
| spelling | doaj.art-8694ec4d77c146a69f093aef771942702023-12-14T06:03:04ZengWileyClinical and Translational Science1752-80541752-80622023-12-0116122744275510.1111/cts.13669Ethnic sensitivity assessment: Polatuzumab vedotin pharmacokinetics in Asian and non‐Asian patients with previously untreated diffuse large B‐cell lymphoma in POLARIXMichael Z. Liao0Rong Deng1Leonid Gibiansky2Tong Lu3Priya Agarwal4Randall Dere5Calvin Lee6Jamie Hirata7Charles Herbaux8Gilles Salles9Chunze Li10Dale Miles11Genentech, Inc. South San Francisco California USAGenentech, Inc. South San Francisco California USAQuantPharm LLC North Potomac Maryland USAGenentech, Inc. South San Francisco California USAGenentech, Inc. South San Francisco California USAGenentech, Inc. South San Francisco California USAGenentech, Inc. South San Francisco California USAGenentech, Inc. South San Francisco California USACHU de Montpellier Montpellier FranceMemorial Sloan Kettering Cancer Center New York New York USAGenentech, Inc. South San Francisco California USAGenentech, Inc. South San Francisco California USAAbstract This ethnic sensitivity analysis used data from the phase III POLARIX study (NCT03274492) to assess polatuzumab vedotin pharmacokinetics (PKs) in Asian versus non‐Asian patients with previously untreated diffuse large B‐cell lymphoma and examined the appropriateness of extrapolating global study findings to Asian patients. PK and population PK (PopPK) analyses assessed polatuzumab vedotin analyte exposures by ethnicity (Asian [n = 84] vs. non‐Asian [n = 345] patients) and region (patients enrolled from Asia [n = 80] vs. outside Asia [n = 349]). In patients from Asia versus outside Asia, observed mean antibody‐conjugated monomethyl auristatin E (acMMAE) concentrations were comparable (1.2% lower at cycle [C]1 postdose, 4.4% higher at C4 predose; and 6.8% lower at C4 postdose in patients from Asia). Observed mean unconjugated MMAE was lower in patients from Asia by 6.5% (C1 postdose), 20.0% (C4 predose), and 15.3% (C4 postdose). In the PopPK analysis, C6 area under the curve and peak plasma concentrations were also comparable for acMMAE (6.3% and 3.0% lower in Asian vs. non‐Asian patients, respectively) and lower for unconjugated MMAE by 19.1% and 16.7%, respectively. By region, C6 mean acMMAE concentrations were similar, and C6 mean unconjugated MMAE concentrations were lower, in patients enrolled from Asia versus outside Asia, by 3.9%–7.0% and 17.3%–19.7%, respectively. In conclusion, polatuzumab vedotin PKs were similar between Asian and non‐Asian patients by ethnicity and region, suggesting PKs are not sensitive to Asian ethnicity and dose adjustments are not required in Asian patients to maintain efficacy and safety.https://doi.org/10.1111/cts.13669 |
| spellingShingle | Michael Z. Liao Rong Deng Leonid Gibiansky Tong Lu Priya Agarwal Randall Dere Calvin Lee Jamie Hirata Charles Herbaux Gilles Salles Chunze Li Dale Miles Ethnic sensitivity assessment: Polatuzumab vedotin pharmacokinetics in Asian and non‐Asian patients with previously untreated diffuse large B‐cell lymphoma in POLARIX Clinical and Translational Science |
| title | Ethnic sensitivity assessment: Polatuzumab vedotin pharmacokinetics in Asian and non‐Asian patients with previously untreated diffuse large B‐cell lymphoma in POLARIX |
| title_full | Ethnic sensitivity assessment: Polatuzumab vedotin pharmacokinetics in Asian and non‐Asian patients with previously untreated diffuse large B‐cell lymphoma in POLARIX |
| title_fullStr | Ethnic sensitivity assessment: Polatuzumab vedotin pharmacokinetics in Asian and non‐Asian patients with previously untreated diffuse large B‐cell lymphoma in POLARIX |
| title_full_unstemmed | Ethnic sensitivity assessment: Polatuzumab vedotin pharmacokinetics in Asian and non‐Asian patients with previously untreated diffuse large B‐cell lymphoma in POLARIX |
| title_short | Ethnic sensitivity assessment: Polatuzumab vedotin pharmacokinetics in Asian and non‐Asian patients with previously untreated diffuse large B‐cell lymphoma in POLARIX |
| title_sort | ethnic sensitivity assessment polatuzumab vedotin pharmacokinetics in asian and non asian patients with previously untreated diffuse large b cell lymphoma in polarix |
| url | https://doi.org/10.1111/cts.13669 |
| work_keys_str_mv | AT michaelzliao ethnicsensitivityassessmentpolatuzumabvedotinpharmacokineticsinasianandnonasianpatientswithpreviouslyuntreateddiffuselargebcelllymphomainpolarix AT rongdeng ethnicsensitivityassessmentpolatuzumabvedotinpharmacokineticsinasianandnonasianpatientswithpreviouslyuntreateddiffuselargebcelllymphomainpolarix AT leonidgibiansky ethnicsensitivityassessmentpolatuzumabvedotinpharmacokineticsinasianandnonasianpatientswithpreviouslyuntreateddiffuselargebcelllymphomainpolarix AT tonglu ethnicsensitivityassessmentpolatuzumabvedotinpharmacokineticsinasianandnonasianpatientswithpreviouslyuntreateddiffuselargebcelllymphomainpolarix AT priyaagarwal ethnicsensitivityassessmentpolatuzumabvedotinpharmacokineticsinasianandnonasianpatientswithpreviouslyuntreateddiffuselargebcelllymphomainpolarix AT randalldere ethnicsensitivityassessmentpolatuzumabvedotinpharmacokineticsinasianandnonasianpatientswithpreviouslyuntreateddiffuselargebcelllymphomainpolarix AT calvinlee ethnicsensitivityassessmentpolatuzumabvedotinpharmacokineticsinasianandnonasianpatientswithpreviouslyuntreateddiffuselargebcelllymphomainpolarix AT jamiehirata ethnicsensitivityassessmentpolatuzumabvedotinpharmacokineticsinasianandnonasianpatientswithpreviouslyuntreateddiffuselargebcelllymphomainpolarix AT charlesherbaux ethnicsensitivityassessmentpolatuzumabvedotinpharmacokineticsinasianandnonasianpatientswithpreviouslyuntreateddiffuselargebcelllymphomainpolarix AT gillessalles ethnicsensitivityassessmentpolatuzumabvedotinpharmacokineticsinasianandnonasianpatientswithpreviouslyuntreateddiffuselargebcelllymphomainpolarix AT chunzeli ethnicsensitivityassessmentpolatuzumabvedotinpharmacokineticsinasianandnonasianpatientswithpreviouslyuntreateddiffuselargebcelllymphomainpolarix AT dalemiles ethnicsensitivityassessmentpolatuzumabvedotinpharmacokineticsinasianandnonasianpatientswithpreviouslyuntreateddiffuselargebcelllymphomainpolarix |