Q: The Multiple Myeloma Research Foundation has had some great successes in its efforts to accelerate and streamline the conduct of clinical trials. Can you share highlights from some of those efforts?
In response to the increasing need to bring novel treatments to myeloma patients, Kathy Giusti founded the Multiple Myeloma Research Consortium (MMRC) in 2004. The consortium is currently composed of 22 academic and large community centers in North America and performs leading myeloma research. The MMRC has performed both company-sponsored and multi-site, investigator-initiated trials and has a well-balanced trial portfolio. Together the MMRC has worked on some pivotal trials for approved drugs such as Kyprolis, Pomalyst, and Empliciti.
To improve the efficiency of and streamline the process for investigator-initiated trials, the MMRC created an IIT platform utilizing a standardized clinical trial agreement that would quickly open studies at multiple sites. In addition, internal resources at the MMRC are dedicated to work with industry partners and staff at the respective MMRC sites to ensure that every part of the process including protocol development, study start-up, and trial accrual is done as efficiently possible. Most importantly, the MMRC strives to open trials faster than industry standards and drive patient enrollment ahead of the projected timelines. Utilizing the infrastructure that has been put into place the MMRC has been able to open over 65 trials with more than 30 novel agents since its inception.
There are two examples that can be highlighted. In one example, there was a company-sponsored trial that involved 9 MMRC sites and 10 non-MMRC sites, which we call a hybrid MMRC study. The MMRC sites opened an average of 111 days faster than the non-MMRC sites. In addition, the MMRC contributed 55 of the 77 patients and closed the study to enrollment before 7 of the 10 non-MMRC sites even became active to enrollment. As a second example one of the recent IITs hit their enrollment target one year ahead of schedule.
Q: What assets and capabilities does the Foundation have that allowed you to achieve these outcomes?
The MMRF has prided itself on breaking down classical barriers that impede drug development by creating new models, such as the MMRC, to bring speed, efficiency and effectiveness to the process. To create better efficiency in the process the MMRC put the following into place:
- Funding support for project managers at each of the MMRC sites. The project managers are an invaluable resource, serving as our “boots on the ground” to help move our studies through each regulatory step as fast as possible and identify patients at each site who may be eligible for a clinical trial.
- A metrics-based award system to determine how efficient each site is at specified steps in the clinical trial process.
- The MMRF has a solid relationship with the FDA and has held roundtable discussions with pharma, academic investigators and clinicians to strategize around important clinical questions and ways to answer them most effectively.
Q: What was the need that MMRF saw that caused it to get involved in this part of the R&D spectrum? What did you feel you could uniquely bring to the table?
In the early 2000s MMRF clearly saw the need to accelerate drug development in multiple myeloma and improve patient outcomes. In order to accomplish this they created the MMRC, a model that integrates academia and industry around the common goal of speeding up multiple myeloma drug development.
As one of its major goals, MMRC accelerated the launch and completion of Phase I and Phase II clinical trials so that new treatments could be delivered to patients as quickly as possible. MMRF has a clear sense of urgency that it brings to all of its undertakings.
Q: What have been the biggest challenges in planning, launching, and sustaining your efforts in this area? What lessons have you learned?
Some of the biggest challenges include:
1) As MMRC trials involve multiple participating sites and multiple companies, multi-party contracting became a significant challenge. Designing a clinical trial agreement template, with standardized language that is acceptable by all of the parties, is critical to expedite the process.
2) Planning and executing single-arm IITs can be time-consuming and inefficient. Therefore designing larger “umbrella” or master protocol designs that test multiple drugs at one time and that are “evergreen” protocols where drugs can be added or subtracted with simple protocol amendments is critical.
Some of the lessons learned include:
1) Even though there have been 10 new drugs approved over 12 years, still about 15-20 percent of patients are not responding to these new treatments making it essential to find additional novel treatments for patients. Speed is important but choosing the appropriate drugs and combinations to test is critical.
2) Building and maintaining strong relationships across all sectors involved is the key to driving towards a cure, but that takes time.
3) Most important, establishing an end-to-end solution in the era of precision medicine is critical to bringing the right drugs to the right patients at the right time.
This is why the MMRF brought forward the MMRF Precision Medicine Model, an end-to-end solution consisting of three major pillars:
- DataBank- Building large datasets of clinical and genomic information including its landmark study CoMMpass, a longitudinal analysis of 1000 newly diagnosed multiple myeloma patients over an eight year course of the disease at the clinical and molecular levels
- Learning Network- In depth analysis of data to identify new targets, outcome biomarkers and testing new hypotheses at the bench
- Clinic- rapidly translating findings to the clinic and establishing a balanced pipeline of trials including molecularly targeted, immune and other novel agents and combinations
Q: What advice would you give other foundations that might be interested in undertaking similar efforts – or other companies interested in working more closely with patient groups on clinical trial planning and conduct?
Foundations need to have well-defined objectives and a solid business plan with the appropriate resources, both internal and external, to start and sustain these efforts. Companies should engage with foundations to better understand patient needs. In addition, foundations as trusted third parties can provide the appropriate forums to discuss clinical trials that would involve combinations of novel agents across various company pipelines and with input from regulatory agencies.
Q: How has MMRF engagement with the patient community benefited these efforts, particularly in terms of recruitment and retention in trials?
The MMRF provides myeloma patients information concerning MMRC and non-MMRC trials through a variety of resources. MMRF nurse specialists are available to answer clinical trial questions and guide myeloma patients through their journey by phone.
In addition an online MMRF CoMMunity Gateway offers patients, caregivers and experts the ability to have conversations on clinical trial options and new advancements in myeloma as a trusted community. Also the MMRF Myeloma Trial Finder makes it easier for myeloma patients to find clinical trials that are the most appropriate for their type of myeloma.
Through these well-developed resources, along with patient/caregiver meetings and print material, MMRF ensures that patients are well informed about clinical trial options.
To learn more about MMRF’s work, read an interview with Founder Kathy Giusti in the New York Times.