Jun 15, 2016

The Druggable Genome and Advancing Precision Medicine

It started with the human genome project1: Decloaking the human DNA and identifying the 3,000-odd genes making up the “druggable genome”—attractive targets for therapeutic intervention—has fueled the drive for precision medicine.2 Rare mutations, a wide range of cancer types, and a rapidly increasing number of targeted therapies in clinical development require genotype-matched clinical therapies. A special session at the American Association for Cancer Research (AACR) 2016 annual meeting profiled ongoing next-generation clinical trials that use broad-based genomic testing to match actionable alterations with available interventions.

Basket trials are designed on the hypothesis that the presence of a molecular marker predicts clinical benefit to targeted therapy independent of tumor histology.3 David Hyman, MD, from Memorial Sloan Kettering discussed the targeted tumor sequencing test, MSK-IMPACT (Integrated Mutation Profiling of Actionable Cancer Targets) that has enabled precision oncology and supported a large clinical trial portfolio of multi-histologic, biomarker-selected basket trials.4, 5

Peter O’Dwyer, MD, focused on the NCI-MATCH (NCI-Molecular Analysis for Therapy Choice), a clinical trial co-developed by the ECOG-ACRIN Cancer Research Group and the National Cancer Institute that aims to analyze 5,000 patients with advanced or refractory solid tumors or lymphomas for genetic mutations, amplifications or translocations, and then assign treatment based on the alteration.6 It is the largest precision medicine cancer trial to date and opened for enrollment in August 2015 across 790 study locations with 10 treatment arms and a projected expansion to 24 or more treatment arms this year. Each treatment arm targets a unique gene abnormality.7

The TAPUR (Targeted Agent and Profiling Utilization Registry) Study presented by Richard L. Schilsky, MD, FACP, FASCO, is a collaborative effort sponsored by ASCO (American Society of Clinical Oncology) and uses the molecular profile of patients with advanced cancer to identify actionable alterations that are known targets or predict sensitivity to a commercially available drug.8, 9 The study provides subjects with approved targeted therapies contributed by collaborating pharmaceutical companies.

In this genomic era of precision oncology, the recent advances in trial design are very encouraging.

At Navicor, we are committed to staying up to date on the latest scientific developments in the oncology community and working together with our clients to turn the latest developments into brands, and patients into survivors.

For more information on how to help grow your brand, please contact Marvin Bowe (marvin.bowe@inventivhealth.com, 267.702.2052).

References

  1. National Human Genome Research Institute. All about the human genome project (HGP). https://www.genome.gov/10001772/all-about-the–human-genome-project-hgp/. Accessed May 13, 2016.
  2. US Department of Health and Human Services. Illuminating the druggable genome (IDG). https://ncats.nih.gov/idg. Accessed May 13, 2016.
  3. Redig AJ and Jänne PA. Basket trials and the evolution of clinical trial design in an era of genomic medicine. J Clin Oncol. 2015;33(9):975-977.
  4. David Hyman. Basket trials. Presented at: The American Association for Cancer Research Annual Meeting; April 16-20, 2016; New Orleans, LA.
  5. MSK Researchers Develop Targeted Test for Mutations in Both Rare and Common Cancers. Memorial Sloan Kettering Cancer Care. https://www.mskcc.org/msk-impact. Accessed May 13, 2016.
  6. Peter O’Dwyer. NCI-MATCH (Molecular Analysis for Therapy Choice). Presented at: The American Association for Cancer Research Annual Meeting; April 16-20, 2016; New Orleans, LA.
  7. National Cancer Institute. Targeted therapy directed by genetic testing in treating patients with advanced refractory solid tumors or lymphomas. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2016. Available from: https://clinicaltrials.gov/ct2/show/NCT02465060.
  8. Richard L. Schilsk. TAPUR (Targeted Agent and Profiling Utilization Registry Study). Presented at: The American Association for Cancer Research Annual Meeting; April 16-20, 2016; New Orleans, LA.
  9. TAPUR Study. American Society of Clinical Oncology. Available at: http://www.tapur.org/. Accessed May 13, 2016.

Sandya Govinda Raju
Medical Director: Navicor, part of the Inventiv Health network.
Spanning a career of over 10 years in healthcare, clinical research, and medical communications, Sandya seamlessly and successfully navigates between academic research and pharmaceutical communications. At Navicor, Sandya leads our Philadelphia department of scientists who focus on drafting medical content and ensuring scientific accuracy. Her career also spans multiple disciplines in translational research.
sandya.graju@inventivhealth.com