1525P - Nab-paclitaxel/gemcitabine with or without epigenetic targeting followed by consolidating immune targeting with durvalumab and lenalidomide in patients with advanced pancreatic ductal adenocarcinoma: Results from the SEPION/AIO-PAK-0118 phase I/II study

Background

Cancer immunotherapy has so far been largely ineffective for patients (pts) with mPDAC. The phase 1/2 SEPION trial (NCT04257448) investigated safety and tolerability of azacitidine (AZA) and romidepsin (ROM) in combination with nab-paclitaxel/gemcitabine (GnP) followed by immune-modulating consolidation with durvalumab and low-dose lenalidomide. Following previously reported dose-escalation (Siveke 2023), we herein report results of dose-expansion and consolidation.

Methods

Eligible pts had untreated mPDAC, measurable disease per RECIST v1.1 and ECOG ≤ 1. Pts with controlled disease after 3 cycles of therapy (part 1) from 3+3 dose escalation of cohorts A (ROM/GnP), B (AZA/GnP) and C (ROM/AZA/GnP), dose expansion (cohort B) or cohort D (GnP without epigenetic targeting) entered immune-modulating consolidation (part 2). Primary endpoint: safety and tolerability. Key secondary endpoints: ORR, DCR, PFS, OS. Tumor, blood and fecal samples were collected for biomarker analysis.

Results

From 05/2020 to 03/2023, of 85 pts screened, 73 pts were enrolled and received at least one dose of any study drug. Cut-off point for data was April 2024. Median (range) follow-up was 9.2 (0.2 - 38.4) months (mos). Median age was 63 (range 31-83) yrs. Dose-escalation showed safety of cohort B (AZA 30 mg/m2), while ROM containing cohorts (A + C) were terminated early. Pts entering immune-modulating consolidation were 4 (A), 27 (B), 1 (C) and 14 (D), respectively. Serious treatment-related adverse events occurred in 54.6% (40/73; part 1) and 17.4% (8/46; part 2) of pts, respectively. 15% of pts presented an AE leading to discontinuation of any study drug. Median PFS/OS were 5.3 (95%CI 4.9-6.6)/10.3 (8.1-14.9) mos (B) and 6.3 (4.3-9.6)/11.7 (8.2 – 23.3) mos (D), respectively. Updated efficacy results and first translational studies will be presented.

Conclusions

GnP with or without AZA followed by sequential durvalumab and lenalidomide after 3 cycles of chemotherapy was safe and feasible. Immunomodulating therapy consolidation shows promising clinical activity in pts with mPDAC.

Clinical trial identification

NCT04257448.

Editorial acknowledgement

Legal entity responsible for the study

GWT-TUD GmbH.

Funding

BMS, AstraZeneca.

Disclosure

J.T. Siveke: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Servier, Immunocore, PSL Group, Novartis, Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Roche, MSD Sharp & Dohme, MCI Deutschland, Falk Foundation; Financial Interests, Personal, Stocks/Shares: FAPi Holding AG; Financial Interests, Institutional, Coordinating PI, Trial support: AstraZeneca, Bristol Myers Squibb, Roche/Genentech; Financial Interests, Institutional, Research Grant, Project support: Abalos Therapeutics, Boehringer Ingelheim, Eisbach Bio GmbH. M. Sinn: Financial Interests, Personal, Advisory Board: AstraZeneca, Servier, Amgen, Sanofi; Financial Interests, Personal, Invited Speaker: BMS, MSD, Pierre Fabre; Financial Interests, Institutional, Local PI: Amgen, AstraZeneca, BMS, BeiGene, GSK, BioNTech; Non-Financial Interests, Leadership Role: AIO Leitgruppe Panreatic Cancer (German Cancer Society); Non-Financial Interests, Member: AWMF Guidelines Pancreatic and Liver Cancer. K. Dorman: Financial Interests, Personal, Financially compensated role, Travel, Accommodations, Expenses, Honoraria: AstraZeneca; Financial Interests, Personal, Financially compensated role, Travel, Accommodations, Expenses: Servier, GSK, Bristol Mayers Squibb. G.M. Siegler: Financial Interests, Personal, Advisory Board: BMS, Novartis, Roche, MSD, Janssen; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Institutional, Local PI: BMS, MSD, AstraZeneca; Non-Financial Interests, Principal Investigator: BMS, MSD, AIO GmbH, IKFZ, AstraZeneca, GLA; Non-Financial Interests, Member: AIO GmbH, DGHO, EORTC, DKG. T. Seufferlein: Financial Interests, Personal, Advisory Board: Cantargia, MSD, Mirati, Servier, Olympus; Financial Interests, Personal, Invited Speaker: Servier, BMS, MSD, Pierre Fabre; Financial Interests, Institutional, Trial Chair: Celgene, Sanofi; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, Lilly; Non-Financial Interests, Member of Board of Directors: German Cancer Society; Non-Financial Interests, Leadership Role, General Secretary: ESDO. J. Trojan: Financial Interests, Personal, Invited Speaker: Amgen, Eisai, Merck Serono, Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer Healthcare, Bristol Myers Squibb, Institute for Quality and Efficiency in Health Care (IQWiG), Ipsen, Lilly ImClone, onkowissen.de, Roche; Financial Interests, Institutional, Research Grant: Roche. D.T. Waldschmidt: Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Eisai, Falk, Incyte, Ipsen, Novartis, MSD, Servier, Taiho Oncology; Financial Interests, Personal, Other, Travel: Lilly. V. Kunzmann: Financial Interests, Personal, Advisory Board, Advisory Role: Amgen, BMS, AstraZeneca, Pierre Fabre Pharma, MSD; Financial Interests, Institutional, Coordinating PI: AstraZeneca, BMS; Non-Financial Interests, Principal Investigator: AstraZeneca, BMS. All other authors have declared no conflicts of interest.