We have located links that may give you full text access.
Clinical Trial, Phase I
Journal Article
Multicenter Study
ABCL-412 Clinical Activity of CC-99282, a Novel, Oral, Small Molecule Cereblon E3 Ligase Modulator (CELMoD) Agent, in Patients With Relapsed/Refractory Non-Hodgkin Lymphoma (R/R NHL) -Results From CC-99282-NHL-001 (NCT03930953) a First-in-Human, Phase 1, Open-Label, Multicenter Study.
Clinical Lymphoma, Myeloma & Leukemia 2022 October
CC-99282, a CELMoD® agent, co-opts cereblon to induce targeted degradation of Ikaros/Aiolos. In preclinical studies, CC-99282 exhibited stronger antiproliferative, apoptotic, and immunostimulatory activities compared with lenalidomide and other CELMoD agents. Here we present results of CC-99282 monotherapy in patients with R/R NHL. This 2-part study comprises CC-99282 monotherapy dose escalation (part A) and expansion ± combination partners (part B). Part A includes patients with R/R diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) that progressed after ≥2 lines of therapy (LOTs) and patients with R/R DLBCL unfit for transplant who have received ≥1 standard LOT. CC-99282 at 0.2, 0.4, 0.6, or 0.8 mg is administered once daily in 3 intermittent, 28-day cycle dosing schedules, with ≥3 patients per cohort. By October 6, 2021, 50 patients received CC-99282 in part A (38 DLBCL, 12 FL; median age 66y; 58% male; 3 median prior LOTs [range 1-8]); 17 remain on treatment, 26 discontinued due to progressive disease. Treatment-related grade 3/4 adverse events were observed in 32 (64%) patients, primarily neutropenia (29 [58%] patients) which was managed with dose modifications and granulocyte colony-stimulating factors. Grade 4 neutropenia during the first month of CC-99282 treatment correlated with prior therapy with ≥4 lines of alkylating agents. All dose-limiting toxicities were hematologic. Maximal recommended doses on the 7/14- and 14/28-days schedules of interest were 0.6 mg and 0.4 mg, respectively. For doses ≥0.4 mg on schedules of interest, responses were durable, and overall response rate was 42% (15/36 evaluable patients; 6 complete and 9 partial responses; 6 FL, 9 DLBCL); responders included patients who progressed on/after cellular therapy and/or immunomodulatory/CELMoD agents. Responses also correlated with early reduction in circulating tumor DNA. CC-99282 was absorbed rapidly with a prolonged median terminal half-life (~50 hours [doses ≥0.4 mg]). Increase in CC-99282 plasma exposure and Ikaros/Aiolos degradation in peripheral T cells were dose-dependent (maximum degradation [>90%] by treatment day 4 [doses ≥0.4 mg]). CC-99282 monotherapy demonstrated a manageable safety profile, with promising efficacy in heavily pretreated patients with R/R NHL. Pharmacokinetic/pharmacodynamic data were consistent with robust/rapid CC-99282-mediated antitumor activity. This BMS-funded study is enrolling patients.
Full text links
Related Resources
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app