Progress Made at ASCO in NCI Master Protocols
Earlier this week, at the 2019 ASCO annual meeting, officials from the NCI, investigators from SWOG Cancer Research Network and our National Clinical Trials Network (NCTN) partners, and executives from the pharmaceutical industry met to talk about ComboMATCH and ImmunoMATCH, the next generation of NCI precision medicine master protocols.
I will toot the SWOG horn a little here. We started much of this in 2014, when SWOG and NCI launched Lung-MAP. Now two more trials are quickly ramping up.
ComboMATCH is an iteration of MATCH, the trial run by ECOG-ACRIN. While MATCH treatments consist of single agents, ComboMATCH will test combinations of targeted agents (as the name implies!), seeking higher response rates.
As with MATCH, ECOG is overseeing the master protocol. However, the four NCTN adult groups – ECOG, SWOG, NRG, and the Alliance – will each run a suite of four to six sub-studies at any given time. Each group has representatives on the trial’s agents and genes working group, the body that will review and prioritize concepts. Dr. Gary Lyman, a SWOG executive officer, is serving as our senior representative to that working group, along with Drs. Jennifer Specht, Ulka Vaishampayan, and Lajos Pusztai.
Dr. Lyman says ComboMATCH drug pairings must be supported with some preclinical or early clinical data and be based on a genomic selection marker, consistent with other precision medicine trials. Sub-studies may also need to be designed to separate activity of one or both agents from the effects of the combination – and multiple stages might be built in.
Interested investigators are encouraged to send concept ideas immediately; The working group will begin their first concept review at the end of next week. To submit, complete the form found here and send it by email to Dr. Lyman at tylzna/ng/serquhgpu/qbg/bet
Meanwhile, development of ImmunoMATCH, or I-MATCH, is coming along as well.
SWOG will design and manage the master protocol for this trial, with Drs. Kenneth Grossman and Katerina Politi overseeing that task, and Dr. Siwen Hu-Lieskovan reviewing and guiding SWOG’s sub-study portfolio that our investigators develop.
The whole concept behind I-MATCH shows how quickly the field of immune-oncology (IO) is growing in scope and sophistication. I-MATCH will have options for patients in the first and second lines, and will include a variety of solid tumor types. Of particular interest are those patients whose tumors are primarily resistant to PD-1 inhibitors and whose cancers progress within the first few months of starting treatment. As with ComboMATCH, I-MATCH will test combinations, including IO/IO, IO/targeted, and IO/chemotherapy.
What will make I-MATCH unique is the way it matches patients to treatment options. Patients will undergo immune profile testing and be directed onto a protocol based on tumor mutation burden and gamma interferon signature. The study team is in the process of defining how best to sort patients based on tumor histology and markers.
ComboMATCH could open as early as the end of 2019, and I-MATCH should open at the end of 2020.
Note as well, our Lung-MAP precision trial expanded six months ago to include patients with all non-small cell lung cancers. At ASCO, Lung-MAP was the subject of three poster presentations, along with a summary talk by Dr. Vali Papadimitrakopoulou, Lung-MAP study chair. Just last month, Lung-MAP opened a new sub-study testing a new immunotherapy combo against standard of care chemotherapy, and the new screening protocol is open at over 500 sites.
These are exciting times! The NCTN is continuing to break new ground in precision medicine clinical research, and SWOG is heavily invested and involved. I am eager for these two new master protocols to launch. Stay tuned, as there is a lot more to come.