scholarly journals Asian race and origin have no clinically meaningful effects on polatuzumab vedotin pharmacokinetics in patients with relapsed/refractory B-cell non-Hodgkin lymphoma

2020 ◽  
Vol 86 (3) ◽  
pp. 347-359
Author(s):  
Rong Shi ◽  
Tong Lu ◽  
Grace Ku ◽  
Hao Ding ◽  
Tomohisa Saito ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Phase 1 ◽  
Single Agent ◽  
Antibody Drug Conjugate ◽  
Asian Race ◽  
Non Hodgkin Lymphoma ◽  
Asian Patients ◽  
Poppk Model ◽  
Phase 1B

Abstract Purpose The CD79b-targeted antibody–drug conjugate polatuzumab vedotin (pola), alone and with chemoimmunotherapy, has clinical efficacy and a tolerable safety profile in B-cell non-Hodgkin lymphoma (B-NHL). We assessed (a) whether exposure from global studies of pola is comparable to Asian patients, and (b) if the recommended pola dose is appropriate in Asian patients based on exposure. Methods The pharmacokinetics (PK) of pola in Asian and global populations was characterized for three analytes (antibody-conjugated monomethyl auristatin E (MMAE) [acMMAE], total antibody, and unconjugated MMAE) in five phase 1b/2 single-agent and combination studies in B-NHL patients (JO29138 [JAPICCTI‐142580], DCS4968g [NCT01290549], GO27834 [NCT01691898], GO29044 [NCT01992653], and GO29365 [NCT02257567]). PK data were compared between Japanese phase 1 JO29138 (JAPICCTI‐142580) and global phase 1 DCS4968g (NCT01290549) studies and between Asian and non-Asian patients in the randomized relapsed/refractory B-NHL cohorts of the phase 1b/2 study GO29365 (NCT02257567). A population PK (popPK) model was used to assess the effects of Asian race and region on acMMAE and unconjugated MMAE exposure. Results PK non-compartmental analysis (NCA) parameters for the key analyte acMMAE in the Japanese JO29138 (JAPICCTI‐142580) and global phase 1 DCS4968g (NCT01290549) studies were similar. In GO29365 (NCT02257567), the phase 1b/2 combination study, mean exposure to the analytes was generally lower in Asian patients (by ~ 9.9 to 17.5%), but not to a clinically meaningful extent. Overall, the popPK model further suggested comparable PK in Asian patients with B-NHL (race or region) versus non-Asian patients. Conclusion Race has no clinically meaningful effect on pola PK. These results (and observations from efficacy/safety exposure–response analyses) support no pola dose adjustments are warranted for Asian patients with DLBCL.

Anti-CD79B Antibody-Drug Conjugate DCDS0780A in Patients with B-Cell Non-Hodgkin Lymphoma: Phase 1 Dose-Escalation Study

2022 ◽  
pp. clincanres.3261.2021
Author(s):  
Alex F. Herrera ◽  
Manish R. Patel ◽  
John M. Burke ◽  
Ranjana Advani ◽  
Bruce D. Cheson ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Dose Escalation ◽  
Phase 1 ◽  
Antibody Drug Conjugate ◽  
Dose Escalation Study ◽  
Drug Conjugate ◽  
Non Hodgkin Lymphoma ◽  
Antibody Drug

scholarly journals Final Results of a Phase 1 Study of Loncastuximab Tesirine in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma

Blood ◽  
2020 ◽  
Author(s):  
Mehdi Hamadani ◽  
John Radford ◽  
Carmelo Carlo-Stella ◽  
Paolo F Caimi ◽  
Erin G Reid ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Dose Escalation ◽  
Cell Lymphoma ◽  
Phase 1 ◽  
B Cell Lymphoma ◽  
Recommended Dose ◽  
Clinical Activity ◽  
Antibody Drug Conjugate ◽  
Non Hodgkin Lymphoma

The prognosis for patients with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL) remains poor, with a need for alternatives to current salvage therapies. Loncastuximab tesirine (ADCT-402) is an antibody-drug conjugate comprising a humanized anti-CD19 monoclonal antibody conjugated to a pyrrolobenzodiazepine dimer toxin. Presented here are final results of a Phase 1 dose-escalation and dose-expansion study in patients with R/R B-NHL. Objectives were to determine the maximum tolerated dose (MTD) and recommended dose(s) for expansion and to evaluate safety, clinical activity, pharmacokinetics, and immunogenicity of loncastuximab tesirine. Overall, 183 patients received loncastuximab tesirine, with 3+3 dose escalation at 15-200 µg/kg and dose expansion at 120 and 150 µg/kg. Dose-limiting toxicities (all hematologic) were reported in 4 patients. The MTD was not reached, although cumulative toxicity was higher at 200 µg/kg. Hematologic treatment-emergent adverse events were most common, followed by fatigue, nausea, edema, and liver enzyme abnormalities. Overall response rate (ORR) in evaluable patients was 45.6%, including 26.7% complete responses (CR). ORRs in patients with diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, and follicular lymphoma were 42.3%, 46.7%, and 78.6%, respectively. Median duration of response in all patients was 5.4 months and not reached in patients with DLBCL (doses ≥120 µg/kg) who achieved CR. Loncastuximab tesirine had good stability in serum, notable anti-tumor activity, and an acceptable safety profile, warranting continued study in B-NHL. The recommended dose for Phase 2 was determined as 150 µg/kg every 3 weeks (Q3W) for 2 doses followed by 75 µg/kg Q3W. Study: NCT02669017.

Avadomide plus obinutuzumab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (CC-122-NHL-001): a multicentre, dose escalation and expansion phase 1 study

2020 ◽  
Vol 7 (9) ◽  
pp. e649-e659 ◽  
Author(s):  
Jean-Marie Michot ◽  
Reda Bouabdallah ◽  
Umberto Vitolo ◽  
Jeanette K Doorduijn ◽  
Gilles Salles ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Dose Escalation ◽  
Phase 1 ◽  
Phase 1 Study ◽  
Expansion Phase ◽  
Non Hodgkin Lymphoma

scholarly journals Venetoclax plus R- or G-CHOP in non-Hodgkin lymphoma: results from the CAVALLI phase 1b trial

Blood ◽  
2019 ◽  
Vol 133 (18) ◽  
pp. 1964-1976 ◽  
Author(s):  
Andrew D. Zelenetz ◽  
Gilles Salles ◽  
Kylie D. Mason ◽  
Carla Casulo ◽  
Steven Le Gouill ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Phase 2 ◽  
Non Hodgkin Lymphoma ◽  
Phase 1B ◽  
Grade 3

Abstract Novel strategies, such as chemosensitization with targeted agents, that build on the success of standard immunochemotherapy show promise for the treatment of non-Hodgkin lymphoma (NHL). Here, we report a phase 1b study investigating dose escalation of the BCL2 inhibitor, venetoclax, in combination with rituximab or obinutuzumab and cyclophosphamide, doxorubicin, vincristine, and prednisone (R-/G-CHOP) chemotherapy in B-cell NHL. Objectives included safety assessment and determination of a recommended phase 2 dose (RP2D). Fifty-six patients were enrolled, most with follicular lymphoma (43%) or diffuse large B-cell lymphoma (DLBCL; 32%). Dose-limiting toxicities were reported in 3/14 patients at the first venetoclax dose (200 mg/d), after which dosing was changed from daily to 10 days per cycle and escalated to 800 mg. A further reduction to 5 days per cycle occurred at the 800-mg dose level in the G-CHOP arm. Cytopenias were predominant among grade 3/4 events and reported at a higher rate than expected, particularly in the G-CHOP arm; however, safety was manageable. Overall response rates were 87.5% (R-CHOP and G-CHOP combinations); complete response (CR) rates were 79.2% and 78.1%, respectively. Most double-expressor (BCL2+ and MYC+) DLBCL patients (87.5%; n = 7/8) achieved CR. Although the maximum tolerated dose was not reached, the RP2D for venetoclax with R-CHOP was established at 800 mg days 4 to 10 of cycle 1 and days 1 to 10 of cycles 2 to 8; higher doses were not explored, and this dosing schedule demonstrated an acceptable safety profile. This regimen is subsequently being evaluated in first-line DLBCL in the phase 2 portion of the study. This trial was registered at www.clinicaltrials.gov as #NCT02055820.

Phase 1b study of venetoclax plus R- or G-CHOP in patients with B-cell non-Hodgkin lymphoma.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 7566-7566 ◽  
Author(s):  
Andrew David Zelenetz ◽  
Gilles A. Salles ◽  
Kylie D. Mason ◽  
Carla Casulo ◽  
Steven Le Gouill ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Non Hodgkin Lymphoma ◽  
Phase 1B
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