TAPUR Study Launches to Evaluate Off-Label Uses of Targeted Cancer Therapies

By Lori Solomon, Editor, Diagnostic Testing & Emerging Technologies

The Targeted Agent and Profiling Utilization Registry (TAPUR) study began recruiting its first patients last month. The trial, the first clinical trial undertaken by the American Society of Clinical Oncology (ASCO), aims to evaluate expanded use of targeted therapies, beyond approved indications, in real-world clinical settings.

While there is growing interest in trying to clinically match molecular alterations to targeted treatments, intermediate and rare gene alterations (those that account for less than five percent and two percent of all alterations, respectively) account for the vast majority of identified alterations. The rarity of these alterations makes conventional clinical trial designs infeasible. Thus, approved drugs may not be indicated for many advanced cancers, despite the presence of a potentially actionable aberration.

TAPUR hopes to overcome some of these challenges by learning from prescription of targeted therapies to patients with advanced cancer whose tumor harbors a genomic variant known to be a drug target, regardless of its approved indication. ASCO argues that this trial enables patients out of standard options to receive targeted therapies they may not otherwise be able to access, while providing both physicians and industry data on genomic test results and off-label drug uses in a real-world setting.

Patients with advanced solid tumors, multiple myeloma or B cell non-Hodgkin lymphoma who have exhausted standard treatment options are eligible to participate. Treating physicians determine based on the tumor’s genomic profile if a study drug may be beneficial. A molecular tumor board (experts convened by ASCO) can provide consultation. Participating pharmaceutical companies (currently Bristol-Myers Squibb, Eli Lilly and Company, Genentech and Pfizer) provide study drugs at no cost. Consented, participating patients (up to 1,030) are followed for drug toxicity and clinical outcomes. ASCO’s drug and safety monitoring board reviews results to determine if a drug is deemed promising for a particular cancer-genomic variant pairing.

TAPUR will enroll participants with tumors that have at least one genomic variant that is potentially targeted by one or more drugs available in the study. Each combination of tumor type, genetic variant and study drug forms one “group.” Initially each group will enroll 10 patients. The drug and safety monitoring board will monitor results. If the initial group has one or fewer responders, enrollment for that group is stopped. However, if there are at least two responders, the study will enroll an additional 18 patients in that group. With seven or more responses, 28 additional patients will be enrolled. This moving protocol is similar to another trial currently underway by the Netherlands Center for Personalized Cancer Treatment.

ASCO is providing infrastructure support for study administration. Syapse’s Precision Medicine Platform is automating all elements of the study workflow including patient registration, eligibility assessment, matching of patients to therapies based on genomic data, drug ordering, data collection, and facilitating the molecular tumor board process. Illumina’s NextBio Clinical and Knowledge Base is supporting case review by the tumor board. Initially, four cancer center networks (the Carolinas HealthCare System’s Levine Cancer Institute, the Cancer Research Consortium of West Michigan, the Michigan Cancer Research Consortium, and the University of Michigan) are recruiting patients, but the study plans to expand geographically later in the year.