Precision Medicine Platform Trial Aims to Develop Treatments for Rare Cancers

Cancer cells, illustration
Credit: JESPER KLAUSEN / SCIENCE PHOTO LIBRARY/Getty Images

Cancer Research UK have announced the launch of the of first UK-based precision medicine platform trial that aims to identify licensed treatment options for adults and children with rare cancers.

The DETERMINE trial will be led by the University of Manchester in collaboration with the University of Birmingham, the Royal Marsden NHS Foundation Trust, and the Christie NHS Foundation Trust. Cancer Research UK’s Centre for Drug Development will sponsor and manage the trial and Roche will provide the first seven targeted therapies for evaluation.

Rare cancers account for 22% of cancer diagnoses worldwide each year, but they “often have few treatment options available and it’s vitally important we increase our research efforts for these patients,” Shamim Kazmi-Stokes, Cancer Research UK’s Project Manager for the DETERMINE trial, told Inside Precision Medicine.

“This trial serves as a platform to provide access to potentially efficacious new therapies for these patients rather than go down the time-consuming compassionate use access route. Those showing efficacy, may ultimately gain approval in these rare indications increasing options for these patients,” Kazmi-Stokes added.

The DETERMINE investigators aim to recruit around 850 people with rare cancers and an identifiable genetic alteration in their cancer that can be targeted by treatments that are already approved for use in other cancer types. Recruitment will take place over a 5-year period, beginning Summer 2022, with each participant being followed-up for at least 2 years.

Participants will initially be eligible if they have mutations in ALK, ROS1, HER2, or BRAF genes, more typically seen in non-small-cell lung cancer, colorectal cancer, breast cancer, and metastatic melanoma, respectively. These mutations are targeted with the corresponding Roche drugs alectinib (Alecensa), entrectinib (Rozlytrek), trastuzumab (Herceptin) plus pertuzumab (Perjeta), and vemurafenib plus pertuzumab (Zelboraf plus Cotellic).

Individuals with tumors that have high tumor mutational burden or microsatellite instability-high or proven constitutional mismatch repair deficiency disposition, that can be targeted with atezolizumab (Tecentriq) will also be eligible.

If the drugs show efficacy in the patients with rare cancers, they can then be submitted for review by the Cancer Drug Fund (CDF).

The CDF “plan to implement a new process via the clinical commissioning group to fast track drugs into the CDF potentially assessing fewer patient numbers to gather more real-world data more rapidly. Ultimately, if a particular drug in a currently unlicensed rare indication shows proven efficacy, it may gain faster approvals in the UK,” Kazmi-Stokes explained.

Although the trial will open with the five treatment arms from Roche, agreements with additional pharmaceutical and biotech partners that offer licensed agents targeting other mutations are expected from early 2022. This will expand the number of treatment options available to people with rare cancers.

DRUP, CAPTUR, and TAPUR are similar “drug rediscovery” trials that are underway in the Netherlands, Canada, and the USA, respectively, but “DETERMINE is the first precision medicine platform trial to assess licensed agents in children, young people and adults with rare tumors,” Kazmi-Stokes remarked.

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