Patient-reported outcomes (PROs) and biomarkers in daNIS-2, a phase III study comparing NIS793 plus nab-paclitaxel/gemcitabine (NG) vs placebo plus NG in first-line (1L) metastatic pancreatic ductal adenocarcinoma (mPDAC).
Authors: Wainberg Zev A. , Macarulla Teresa , Golan Talia , Ikeda Masafumi , Milella Michele , Taieb Julien , Wang Liwei , Gyambibi Nana , López Eva M. , Bento Pereira da Silva Ana , Polydoros Fotis , D'Alessio Denise , O'Reilly Eileen Mary 
Published: January 2023

TPS767 Background: The 5-year survival rate for mPDAC is <5% with current standard-of-care (SOC) chemotherapies, and this period is often associated with a high symptom burden. Currently, targeted treatment options are only available to a minority of patients (pts) with mPDAC. Here, we present the PRO and biomarker objectives of daNIS-2, a randomized, double-blind, Phase III study (NCT04935359) of the anti–TGF-β monoclonal antibody NIS793 in combination with SOC chemotherapy in pts with 1L mPDAC. Methods: Eligible pts are adults (≥18 years) with previously untreated mPDAC who are eligible for treatment in the 1L setting and not amenable to potentially curative surgery. The daNIS-2 study includes safety run-in and randomized parts. In the safety run-in part, pts will receive a combination of NIS793 (2100 mg intravenous [IV] every 2 or 4 weeks) and NG (gemcitabine 1000 mg/m2 IV; nab-paclitaxel 125 mg/m2 IV; each on Days 1, 8, and 15 of a 28-day cycle). Following dose confirmation, ~480 pts will be randomized to one of two treatment arms (~240 pts per arm): an investigational arm (NIS793 + NG) or a control arm (placebo + NG). The primary objective of the randomized part is to compare overall survival between arms. Secondary objectives (randomized part only) include the evaluation of health-related quality of life (using PROMIS-29 v2.1 and EQ-5D-5L). Additional PROs will be assessed as exploratory endpoints (using PRO-CTCAE, PGIC, PGIS, and FACT-GP5). Safety endpoints include the incidence and severity of adverse events, changes in laboratory parameters, vital signs, body weight and cardiac assessments, dose adjustments, and dose intensity. Biomarker assessments will be carried out as exploratory objectives; biomarker assessments in baseline or archival tumor biopsies will explore the relationships of programmed death-ligand 1 expression, CD8, and tumor burden with clinical efficacy endpoints. Recommended, on-treatment biopsies (Cycle 3 and at the end of treatment) will investigate the effect of NIS793 on the tumor microenvironment, immune cell population changes, gene expression, and potential mechanisms of NIS793 resistance. Circulating tumor DNA will be analyzed in serial blood samples (Day 1 of Cycles 1–3, every two cycles for 52 weeks, then every three cycles) to monitor disease and identify/correlate gene-specific oncogenic alterations with clinical efficacy. Additional peripheral assessments will include measurements of cytokine levels relating to clinical/immune responses and nucleic acids to evaluate the effects of TGF-β blockade. This study is ongoing and plans to enroll pts from 145 sites across 28 countries. The first pt was treated on October 20, 2021. Clinical trial information: NCT04935359 .