Mastering the Master Protocol
Our flagship master protocol, Lung-MAP just screened its 4,000th patient and is about to enroll its 1,000th patient to a sub-study. These numbers are impressive! They also demonstrate master protocols are here to stay. In fact, SWOG and the NCTN continue to refine Lung-MAP and apply its lessons to a new crop of master protocols. I’d like to briefly update you on the four SWOG is now working on.
The original Lung-MAP study opened in June of 2014, and in the intervening seven years the Lung-MAP team has:
- explored new drugs from at least 12 pharmaceutical partners
- evaluated 13 combinations of agents
- published 15 manuscripts reporting on the trial and/or sub-study results
- given 23 conference presentations devoted to MAP
- opened the study at a total of 966 sites
- stored more than 10,000 biospecimens in a public bank
- identified 300 genes with alterations
And if the list above isn’t a sufficient set of numbers, a group of Lung-MAP statisticians and investigators is now engaged in a project tracking the demographic and socioeconomic characteristics of the thousands of Lung-MAP participants, to gauge whether they are fully representative of the entire population of patients diagnosed with lung cancer in the U.S.
MyeloMATCH is SWOG’s soon-to-be-launched master protocol for patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML).
It’s truly a collaborative effort, with a senior scientific council (SSC) that includes all the divisions of the NCI that are involved in clinical trial development, along with representatives from the Bone Marrow Transplant Clinical Trials Network, all of the U.S. cooperative groups, and the Canadian Clinical Trials Group. The SSC is led by Dr. Harry Erba, chair of SWOG’s Leukemia Committee, and Dr. Mark Litzow of the Mayo Clinic and ECOG-ACRIN.
At the spring group meeting, the MyeloMATCH team reported having discussed 13 separate agents in meetings with potential pharmaceutical partners and having signed four cooperative research and development agreements (CRADAs), with other CRADAs in process.
I’m excited to report here that the study is moving closer to activation. The concept for the master screening and reassessment protocol, led by SWOG, was approved by CTEP in the spring. The NCI is currently hard at work building some of the infrastructure that will support this master protocol (and others), such as finalizing contracts with laboratories and building the IT systems for data capture, registration, informatics, and so on.
The NCI’s Leukemia Steering Committee has also approved concepts for two MyeloMATCH sub-studies. We hope to see MyeloMATCH open across the NCTN before the year is out.
The ImmunoMATCH, or iMATCH, study is now in development as our first precision medicine master protocol focused on immunotherapy. The study is led by SWOG’s Immunotherapeutics Committee, under the direction of Drs. Siwen Hu-Lieskovan and Katerina Politi.
iMATCH will perform prospective molecular profiling for all patients based on a set of well validated assays. This iMATCH central assay platform now includes two panels of tests:
- whole exome sequencing, which allows a calculation of tumor mutational burden and identifies specific variants that may be treatable, and
- gene expression profiling, which generates a tumor inflammation signature score
Before this master protocol can be launched, however, a pilot study must be conducted to test the feasibility of using the iMATCH assay platform for real-time assignment of treatments to patients. That pilot, S2101 (also known as the BiCaZO trial), is now approaching the end of the protocol development process, and final CTEP approval is expected soon. Watch for it to be activated later this year!
The ComboMATCH study is being led by ECOG-ACRIN as a successor to the NCI-MATCH study. As its name suggests, this master protocol will test combinations of targeted agents to see if they achieve higher response rates in cancers than single agents alone.
SWOG Executive Officer Dr. Gary Lyman is overseeing SWOG subprotocols to be run within ComboMATCH. Two of those subprotocols, EAY191-S3 (testing paclitaxel and ipatasertib in patients with AKT-altered advanced non-breast solid tumors) and EAY191-S4 (testing MRTX-894 with or without afatinib in patients with cancers with mutated KRAS G12C) are now being drafted. A third SWOG subprotocol, EAY191-S5 (testing infigratinib and alpelisib in patients with gynecologic or urothelial cancers with an FGFR2-3 activating mutation or fusion), is under CTEP review. Finally, a fourth SWOG concept must complete a phase I study in the ETCTN before being considered for a ComboMATCH sub-study.
We’ve come a long way from the launch of Lung-MAP as the NCI’s first precision medicine master protocol. The FDA now provides formal guidance on master protocols, and even many pharmaceutical companies now run them. I am proud that SWOG led the way and continues to innovate.