Second/third-line treatment (Tx) options are limited for pts with NPC. The efficacy and safety of CC-486 were assessed using Simon’s optimal 2-stage design in a phase 2 study. The predefined criterion for advancement to stage 2 (> 4 complete/partial responses) was not met. Here, we present final results from stage 1.
The single-arm, open-label study (NCT02269943) included pts with locally advanced/metastatic NPC who had ≥ 1 prior Tx, including ≥ 1 platinum-containing regimen. Pts received CC-486 300 mg orally on d 1-14 of a 21-d cycle until disease progression/unacceptable toxicity. The first 6 Asian-Pacific (AP) pts received CC-486 200 mg; if well tolerated, subsequent AP pts received 300 mg. Primary endpoints (per independent reviewer assessment): overall response rate, progression-free survival. Key secondary endpoints: overall survival, disease control rate, safety, pharmacokinetics (PK).
Median age of 36 enrolled pts was 54.0 y. Most were male (81%), had ECOG PS of ≤ 1 (97%), and had ≥ 2 prior systemic anticancer Tx (58%); 36% were AP. Pts received a median of 7.0 Tx cycles; 44% had ≥ 1 dose interruption and 39% had ≥ 1 dose reduction. 22 pts died: 1 on- and 21 post-Tx (> 28 d after last dose); 18 died due to disease complications. The table shows efficacy outcomes. PK analysis showed rapid absorption; exposure was comparable between doses. However, large inter-pt variability and small pt numbers did not allow definitive conclusions. All 36 safety-evaluable pts had ≥ 1 Tx-emergent adverse event (TEAE). Common TEAEs included vomiting (72%) and nausea (67%). Common grade 3/4 TEAEs included neutropenia (33%) and febrile neutropenia (11%).
The safety profile of CC-486 in pts with NPC was consistent with that in other solid tumors and of azacitidine. CC-486 monotherapy did not show sufficient clinical activity in the selected pt population to support further development in these pts.Table: 1071P
|Primary Endpoints||Efficacy-Evaluable Population (n = 25)|
|Overall response rate, n (%)||3 (12)|
|Partial response||3 (12)|
|Median progression-free survival (90% CI), mo||4.7 (3.1 - 7.3)|
|Disease control rate, n (%)||13 (52)|
|Median overall survival (90% CI), mo||18 (14.8 - not reached)|
Clinical trial identification
Legal entity responsible for the study
Medical writing assistance was provided by Rebecca Tweedell, PhD, MediTech Media, Ltd, funded by Celgene Corporation. All listed authors were fully responsible for all content and editorial decisions for this abstract.
R. Mesia Nin: Advisory role: AstraZeneca, Merck, MSD, BMS; Conferences fee: BMS, Merck. P. Bossi: Consultant/advisory and/or lectures: AstraZeneca, Kyowa Kyrin, Merck, Mundipharma, Roche; Travel coverage: Merck. L.F. Licitra: Consultant/advisory and/or lectures: AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Debiopharm, Eisai, Merck Serono, MSD, Novartis, Roche, Sobi; Research funds to institution: AstraZeneca, Boehringer Ingelheim, Eisai, Merck Serono, MSD, Novartis, Roche; Travel coverage: Bayer, BMS, Debiopharm, Merck Serono, MSD, Sobi. P. Chen: Employee, stock units and stock options: Celgene. J. Miller: Employee, holds company stock: Celgene Pharmaceutical Company. L.L. Siu: Research funding (to institution): Celgene. R. Haddad: Consulting: BMS, Merck, Pfizer, Celgene, Genentech, AstraZeneca; Research support: BMS, Merck, Pfizer, Genentech, AstraZeneca. All other authors have declared no conflicts of interest.