Abstract Background The MORPHEUS platform comprised multiple open-label, randomized, phase Ib/II trials to identify early signals with different treatment combinations across multiple cancers. MORPHEUS-PDAC (NCT03193190) evaluated atezolizumab combinations in pancreatic ductal adenocarcinoma (PDAC). We describe outcomes with atezolizumab plus either motixafortide, cobimetinib, or two simlukafusp alfa regimens. Methods Eligible patients with advanced, pretreated PDAC were randomized to receive second-line (2 L) atezolizumab plus either motixafortide (BL8040; n = 15), cobimetinib (n = 14), simlukafusp alfa every 2 weeks (q2w; n = 15), or simlukafusp alfa every 3 weeks (q3w; n = 16); or control (mFOLFOX6 n = 25 or gemcitabine plus nab-paclitaxel n = 25). Patients experiencing disease progression or toxicity who met eligibility criteria were enrolled to receive third-line (3 L) atezolizumab plus cobimetinib (n = 14), or atezolizumab plus simlukafusp alfa q2w (n = 1) or q3w (n = 6). Primary endpoints were objective response rates (ORRs) per RECIST 1.1 and safety. Results ORRs were 7.1% with atezolizumab-simlukafusp alfa q2w, 8.7% with mFOLFOX6 (both 2 L; 0% in other arms), 14.3% with atezolizumab-cobimetinib, and 16.7% with atezolizumab-simlukafusp alfa q3w (both 3 L). Grade 3-5 adverse event rates were 53.3% (2 L atezolizumab-motixafortide), 64.3% (2 L atezolizumab-cobimetinib), 57.1% (2 L atezolizumab-simlukafusp alfa q2w), 53.3% (2 L atezolizumab-simlukafusp alfa q3w), 63.0% (2 L mFOLFOX6 or gemcitabine-nab-paclitaxel), 50.0% (3 L atezolizumab-cobimetinib), and 100% (3 L atezolizumab-simlukafusp alfa q3w). Conclusions The overall safety of atezolizumab combinations was manageable and consistent with each agent’s known safety profile. This novel trial design enabled rapid evaluations of three atezolizumab combinations; all had limited efficacy as 2 L or 3 L treatment for metastatic PDAC. New treatments are needed to improve outcomes in previously treated PDAC.
Manji et al. (Tue,) studied this question.