Abstract PR013: Navlimetostat (BMS-986504) with or without gemcitabine (GEM) + nab-paclitaxel (nab-P) in patients (pts) with pancreatic ductal adenocarcinoma (PDAC) and homozygous MTAP deletion (
Ben George, Konstantinos Leventakos, Meredith S. Pelster, Jordi Rodón, Kyriakos P. Papadopoulos, Alexander I. Spira, Kathryn C. Arbour, Cesar A. Perez, Hani M. Babiker, Pasi A. Jänne, Richard Zuniga, Scott Paulson, Tanios Bekaii-Saab, Sreenivasa Chandana, Mandana Kamgar, Lars D. Engstrom, Antonella Mazzei-Abba, Alicia Cheong, Hong Shi, Jason T. HenryAbstract
Background:
In the phase 1 CA240-0007 study, navlimetostat (MTA-cooperative PRMT5 inhibitor) was well tolerated and had antitumor activity in pts with MTAP-del advanced solid tumors, including PDAC. Here, we report updated clinical outcomes with navlimetostat monotherapy and initial efficacy and safety data for navlimetostat + GEM + nab-P in substudy 3 (SS3) of pts with PDAC.
Methods:
Pts with MTAP-del PDAC and other advanced solid tumors and no available curative intent treatment (Tx) were enrolled; 7 doses of navlimetostat monotherapy (50–800 mg) in dose escalation and 3 doses (200, 400, or 600 mg) in dose expansion were evaluated. In the SS3 combination cohort, pts with advanced PDAC received navlimetostat 200 mg QD and GEM 1000 mg/m2 Q1W + nab-P 100 mg/m2 Q1W on days 1, 8, and 15 of a 28-day cycle. Objective response rate (ORR), disease control rate (DCR), duration of response (DOR), time to response (TTR), and safety were assessed.
Results:
As of 22 Sept 2025 (median [m] follow-up [f/u], 15.4 mo), 46 pts with PDAC received navlimetostat monotherapy: in clinical activity–evaluable pts (n = 40), navlimetostat monotherapy continued to show durable antitumor activity across all doses (ORR = 18%; mDOR = not reached [NR]), and at the 400- and 600-mg doses of interest (ORR = 24% [6/25]; mDOR = NR). In SS3 (n = 11; mf/u, 6.6 mo), antitumor activity was seen with navlimetostat + GEM + nab-P (ORR = 46%; DCR = 73%; mDOR = NR; mTTR = 4.6 mo). Of all 164 pts who received navlimetostat monotherapy, 14% had grade (gr) ≥ 3 Tx-related adverse events (TRAEs); 2% had TRAEs leading to discontinuation (d/c). In SS3, 64% had gr ≥ 3 TRAEs, 54% had navlimetostat TRAEs (gr ≥ 3, 0%; no related d/c), and 18% had TRAEs leading to d/c of ≥ 1 Tx agent, with AEs as expected based on safety profiles of the individual agents.
Conclusions:
Navlimetostat monotherapy showed durable antitumor activity and was well tolerated in pts with heavily pretreated advanced PDAC. Initial data of navlimetostat + GEM + nab-P showed promising antitumor activity and manageable safety, supporting further evaluation of navlimetostat in pts with MTAP-del PDAC. Analysis of two additional escalating dose cohorts in CA240-0007 SS3 is ongoing and the phase 2/3 MountainTAP-30 study of navlimetostat + GEM + nab-P is currently enrolling.
Encore presentation:
These data were originally presented at the 2026 American Association for Cancer Research (AACR) Annual Meeting. The AACR Annual Meeting is the original forum for presentation, and the Proceedings of the AACR are the original publication source.
Citation Format:
Ben George, Konstantinos Leventakos, Meredith S. Pelster, Jordi Rodón, Kyriakos P. Papadopoulos, Alexander I. Spira, Kathryn C. Arbour, Cesar A. Perez, Hani M. Babiker, Pasi A. Jänne, Richard Zuniga, Scott Paulson, Tanios Bekaii-Saab, Sreenivasa Chandana, Mandana Kamgar, Lars D. Engstrom, Antonella Mazzei-Abba, Alicia Cheong, Hong Shi, Jason T. Henry. Navlimetostat (BMS-986504) with or without gemcitabine (GEM) + nab-paclitaxel (nab-P) in patients (pts) with pancreatic ductal adenocarcinoma (PDAC) and homozygous MTAP deletion (MTAP-del) from CA240-0007 [abstract]. In: Proceedings of the AACR Conference on Pancreatic Cancer: New Frontiers in Biology and Therapeutic Development; 2026 Sep 25-28; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(18_Suppl_2):Abstract nr PR013.