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Montreal, and McGill University. This observational study concluded that prospective genomic profiling of
advanced pancreatic adenocarcinoma is feasible and provides a platform to better understand
chemotherapy response among patients with different genomic/transcriptomic subtypes [30,31] .

Precision-Panc (NCT04161417) was founded in 2017 in the U.K., bringing together the expertise of several
Universities, Cancer Research UK research institutes, and the National Health Service . A master protocol
[32]
provides extensive molecular profiling and is a “portal” to sub-studies referred to as PRIMUS (Pancreatic
canceR Individualised Multi-arm Umbrella Study). Precision-Panc enrolls patients with diagnosed or
suspected pancreatic adenocarcinoma who undergo a biopsy for molecular profiling to determine their
eligibility and enrollment in a PRIMUS substudy. The various PRIMUS studies allow for the enrollment of
patients with different stages of pancreatic adenocarcinoma and look for predictive biomarkers to standard-
of-care chemotherapy as well as targeted agents, immunotherapies and other investigational drugs.

2. Immunotherapy platforms

REVOLUTION (NCT04787991), an exploratory platform in the phase I setting sponsored by the Parker
Institute for Cancer Immunotherapy and the Cancer Research Institute, opened in 2021 at seven sites within
the U.S. REVOLUTION enrolls treatment-naïve patients with metastatic pancreatic adenocarcinoma and
tests combination approaches that include immunotherapy. An exploratory platform, REVOLUTION can
add and drop investigational arms based on results. The two-stage design allows for early assessment of
predictive biomarkers, safety and efficacy, followed by an expanded second stage to confirm the earlier-
stage observations.

Morpheus-Pancreatic Cancer, a Study of Multiple Immunotherapy-Based Treatment Combinations in
Participants with Metastatic Pancreatic Ductal Adenocarcinoma (NCT03193190), is a phase Ib/II clinical
trial sponsored by Hoffmann-La Roche that opened at 27 study locations in 2017. Morpheus-Pancreatic
Cancer evaluates multiple immunotherapeutic approaches for the treatment of patients with metastatic
pancreatic adenocarcinoma. Who have received no prior treatment or have received one treatment
regimen. The platform nature of this trial allows new investigational arms to be added as preclinical
and clinical evidence suggests their potential efficacy, and arms will be removed from the study due to
futility.

3. Adaptive platform trials

Trials using adaptive designs are gaining traction in the pancreatic cancer field after their success in other
cancer types. The breast cancer I-SPY 2 study (Investigation of Serial Studies to Predict Your Therapeutic
Sesponse with Imaging and Molecular Analysis 2 - NCT01042379) was launched in 2011 and continues to
enroll patients and set examples for adaptive platform trials in cancer . The GBM AGILE (Glioblastoma
[33]
Adaptive Global Innovative Learning Environment - NCT03970447) adaptive platform clinical trial is
testing experimental therapies for patients with glioblastoma and brought several innovations to the
[34]
platform trial design . Based on the response-adaptive nature of the trial, investigational treatments can
progress through the trial based on their efficacy in either/both first-line patients or those experiencing a
recurrence, and therapeutic arms will drop from the trial if not found to be effective in either patient
population. The GBM AGILE trial is designed to be conducted in two stages: the screening stage is intended
to identify investigational treatments that show benefit over standard-of-care control arms and to identify
the patient population(s) for which the arm is efficacious; then, the confirmatory stage involves fixed
randomization to validate the findings in the patient population(s) identified through the screening phase
and prepare the treatment for registration for the approval process. Lessons learned from the design and