Abstract PO-050: Precision Promise (PrP): An adaptive, multi-arm registration trial in metastatic pancreatic ductal adenocarcinoma (PDAC)

Abstract

Abstract Background: Drug development in PDAC has been disappointing with an extremely low trial success rate despite considerable effort. PrP is a transformative, adaptive clinical trial platform that attempts to correct this by continuously and rapidly evaluating novel therapeutic options while maximizing the probability of patient (pt) randomization to an experimental treatment and nurturing enhanced cooperation among groups representing pt advocacy, pharmaceuticals, translational/clinical academia, and the FDA. This patient-centric study represents a fundamental shift in drug development for PDAC in the United States and aims to become the largest Phase 2/3 registrational study ever launched in this disease. Methods: PrP (NCT04229004) is a clinical trial platform sponsored by the Pancreatic Cancer Action Network (PanCAN) and funded solely through non-government sources. The protocol was finalized based on the FDA 2020 guidance document regarding "complex innovative designs" in registration trials https://www.fda.gov/media/130897/download. It utilizes adaptive randomization along with several trial design and Bayesian statistical innovations provided by Berry Consultants LLC. All pts undergo pre-and on-treatment biopsies with state-of-the-art genomic, transcriptomic, and immune analysis, along with collection of blood samples for research purposes throughout the study. Pts are managed using novel standardized supportive care techniques, and PrP contains 3 sub-protocols involving quality of life, sarcopenia and actigraphy. PrP was launched in 2020, and currently includes 20 US sites. Focused on both 1st and 2nd line treatment of metastatic PDAC, PrP uses an adaptive platform design with 30% of pts randomized between one of the 2 standard of care control arms (gemcitabine + nab-paclitaxel and mFOLFIRINOX) and 70% to experimental arms, currently either SM-88, a cancer metabolism-based agent (Tyme Inc); or Pamrevlumab, an antibody inhibiting the activity of the connective tissue growth factor (Fibrogen Inc.) The study is ongoing with >100 pts enrolled to date. The Data and Safety Monitoring Committee regularly reviews the data and continues to recommend that the trial proceeds as planned. New study arms will be added after review by an Arm Selection Committee that assesses the validity of the treatment target and the adequacy of the preexisting pre-clinical and clinical data. An additional experimental arm is anticipated in 2021. Conclusion: Compared to traditional trial designs, PrP offers several advantages: multiple investigational treatments can be evaluated in parallel over time; only ~ 175 pts per experimental arm required to initiate a regulatory registration; and increased learning from every patient during the trial, altogether resulting in both time saving and a 30-50% cost saving. In effect, PrP has created an entirely new “learning community” and can substantially accelerate drug development for PDAC. Citation Format: Vincent J. Picozzi, Anne-Marie Duliege, Anirban Maitra, Manuel Hidalgo, Andrew Eugene Hendifar, Gregory L. Beatty, Sudheer Doss Doss, Regina Deck, Lynn M. Matrisian, Julie Fleshman, Diane M. Simeone. Precision Promise (PrP): An adaptive, multi-arm registration trial in metastatic pancreatic ductal adenocarcinoma (PDAC) [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-050.