clinical trials

What is the key to getting a coronavirus vaccine? “Manufacturing,” says today’s guest, Jeff Stein of Cidara Therapeutics.

Jeff joined us just last fall to talk about his company’s exciting new technology, an immunotherapy, that is a universal flu preventative and therapy. Yes, you read that right. A universal flu preventative.

So we were eager to have Jeff on the podcast again and ask the burning $64 million question: Will Cidara’s technology work on the coronavirus? Indeed, it will. Jeff says the company has a clinical development candidate, CD377, which will work on all members of the coronavirus family.

While Jeff is here, he gives an update on the various vaccine programs going on around the world, including the mRNA product we all heard about this week from Moderna Therapeutics.

Is Jeff as optimistic as President Trump about having a vaccine by end of year?

“It’s possible, but not probable.”

As we begin the countdown to the new year, we take a look back at 2015 in cancer research, treatment and prevention. Mendelspod is increasingly becoming known for the coverage of genomics and precision medicine, and cancer as a disease area offers a specific window whereby we can look at practical outcomes.

Anna Barker is the director of the National Biomarker Development Alliance (NBDA). Formerly the deputy director of the National Cancer Institute (NCI), she has worked on cancer her entire career and seen first hand the triumphs and setbacks. Last month at the National Press Club in Washington, D.C., Anna announced the creation of GBM-AGILE, a new kind of clinical trial for a very tough, rare cancer, glioblastoma multiforme. The project is the culmination of the work of Anna and many others to come up with a better system for validating biomarkers. This single trial is a global endeavor and already becoming a "movement" in cancer research with over a hundred and forty experts getting involved. Folks at the FDA are saying that GBM AGILE “raises the bar for clinical trials.”

Along with new ways of doing clinical trials, 2015 has also seen the explosion of new blood-based cancer tests known as liquid biopsies. Still mostly research projects, these tests will potentially offer patients a non-invasive alternative to expensive and painful solid tumor biopsies and offer the promise of someday improving cancer screening and prevention.

Immunotherapy drugs continued to dominate the list of FDA cancer drug approvals in 2015 with the first approval of an oncolytic virus therapy and the first approval of combination immunotherapy. In today’s interview, Anna reminds us that the recent breakthroughs in immunotherapy are the result of a 40 year journey. She goes on to question the herd mentality reflected in the over pursuit of certain targets.

Anna wraps up her review by pointing out the opportunity to go after rare cancers, such as GBM and some childhood cancers. She says the more common cancers such as the big epithelial cancers—breast and lung— are dauntingly complex with "gazillions of mutations.” But with rare cancers, “we can follow the genomic changes through to the cells, to the organs, and to the organism. I’m thinking that we should all begin to take a careful look at some of the rare cancers,” she concludes.

It’s taken some time, but the NCI is finally sponsoring a big time clinical trial for cancer where the patients are organized by the genomic pathway that defines their cancer rather than the organ type.

"Instead of being a breast cancer trial, or a colorectal cancer trial, or the usual construct that’s been used, this one is obtaining biopsy specimens from patients with a whole variety of differing tumor types, evaluating them with a standardized platform to identify abnormalities, and then linking those abnormalities to arms in the trial with drugs targeted to those abnormalities. This is a completely new way of doing a clinical trial and becomes an important step in moving forward a precision medicine cancer therapy approach,” says today's guest, Stanley Hamilton, head of Pathology and Laboratory Medicine at MD Anderson Cancer Center.

How are the four centers participating in the trial going about selecting patients for this new trial? And what pathways does Stanley foresee dominating the trial?

Stanley’s lab has chosen to use Thermo Fisher’s Ion sequencers to characterize the patients’ genomic pathways. Why? Find out the answer to these questions in today’s interview with one of the leading PI’s for this unique clinical trial.

We perform therapeutic and diagnostic clinical trials to learn the safety and efficacy of drugs and tests in a clinical setting.  Typically, we think about the biospecimens in a clinical study in terms of operational requirements such as sample collection, processing, storage and analysis.  Our ability to obtain and test high quality patient samples is an important consideration during the design of clinical research programs and may significantly limit the questions that we can ask in trials. 

For example, our ability to develop drugs for precision medicine in diseases such as cancer depends on access to high quality samples.  The fundamental elements of a trial are the objectives--what questions we intend to address--and the endpoints--what will be measured to answer those questions.   Trials are also defined by the patient population or the inclusion and exclusion criteria determining who is enrolled.   Successful clinical studies require careful planning and design of the study protocol to ensure that the study is feasible and that we capture the lessons learned.  Often, endpoints rely on patient samples for laboratory testing. 

Patient enrollment may require rapid laboratory testing for a molecular or genetic alteration to meet the inclusion criteria.  Researchers also collect patient samples for long term storage for future analysis in the hope that advances in technologies and disease knowledge will open new opportunities.  These study endpoints require robust biospecimen planning during the early development of research programs all the way through to the medical writing of the study protocol.   Study planning is typically based upon experience and expertise.  However, the industry is more frequently utilizing best practices and data-driven analytics and modeling. These tools will improve our planning and preparations for biomarker-driven trials that require biospecimens.

Targeted therapeutics and drug candidates that will rely on patient laboratory test results are becoming common in oncology and other diseases.  Diseases are also being reclassified by molecular biomarkers and complex laboratory tests.  As a result, the biospecimen considerations that have been discussed in the ongoing Biospecimen Series at Mendelspod are becoming critical success factors for drug development. 

In the planning stages we often would like to target a small patient population who may greatly benefit from a new drug compared to the general population.  We then have to ask if we can identify, test and enroll those patients if the samples for testing are difficult to obtain or unstable for shipment and testing.  Similarly, we may have a novel drug with a new mechanism of action that promises to address a critical clinical need.  In this situation we are often limited by the test to certain sample types that may cause a great deal of patient inconvenience or duress.   Difficulties in obtaining  repeated tumor biopsies is one example that has resulted in the development of tests that rely on surrogate samples that may be obtained from the blood.  These considerations often restrict many of our options for study designs include choice of diseases, patient populations and regions or clinical sites. These restrictions also impact the patient journey in the trial. 

Trial protocols summarize the collection and use of samples in a table or schedule of events or assessments.  What may appear to be a simple table, ultimately impacts the patient experience and determines trial feasibility and success.  Researchers must balance the potential knowledge gained, time, cost and risk to maximize the benefit of the study to current and future patients.  Biospecimen planning is increasingly an important part of this equation.  The Mendelspod series Back to Basics: Improving Biospecimens supports a greater understanding of the challenges and opportunities for improving how we utilize critical patient samples.  These improvements will also enable more powerful clinical studies, addressing challenging clinical questions and advancing novel drugs and diagnostics.

Guest:

Diane C. Farhi,, MD, Senior Medical Director, Quintiles Laboratories Bio and Contact Info

Listen (6:37) Tracking clinical samples around the world

Listen (5:34) How to measure sample stability

Listen (3:37) New software needed

Listen (5:07) Challenges from the increase in DNA sequencing

As we’ve been uncovering in our special series, Back to Basics: Improving Biospecimens, the issues around biosample collection, storage, and delivery here in the U.S. can be overwhelming. But Diane Farhi and her team have to manage on a global scale at Quintiles, the world's largest CRO. Who better to take us into the practical issues around sampling?

'Harmonization' is the name of the game in dealing with a global laboratory, says Diane, the Senior Medical Director at Quintiles. Diane and her team are dependent on a world wide delivery system, and that can bring with it many variables which impact samples.

“The whole issue of transport--how long it takes, what the temperature variability is within the package, impacts of alterations in flight schedules due to natural disasters and strikes and other event--all impacts the quality of our specimens when they finally arrive at one of our global laboratories,” she says.

In today’s interview, Diane shares some of the ways that the team at Quintiles mitigates the sampling issues that lie beyond their control. She also details some of the new challenges that have come with the dramatic increase in RNA and DNA sequencing.

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