Jun 04, 2021
By Katherine H. Crawford, MA, PMP, ASCO Communications
It was a rather audacious proposal in 2015 for a professional medical society: design, create, and implement a national clinical trial that would allow as many patients as possible to participate. The goal: gather real-world evidence about which anticancer treatments approved by the U.S. Food and Drug Administration are or aren’t working in patients with solid tumors, depending on the specific genomic profiles of the individual tumors.
With ASCO’s Targeted Agent and Profiling Utilization Registry (TAPUR™) Study (ClinicalTrials.gov identifier: NCT02693535), each of the targeted therapies is being administered to treat a disease other than the specific indication for which it was approved by the Food and Drug Administration (FDA). In other words, patients are being treated based on the genomic profiles of their tumors rather than their disease types—the very definition of precision medicine.
Yes, the proposal was audacious but visionary, like so many of ASCO's programs over the years, such as QOPI® and CancerLinQ®, and organizations in other countries have taken notice, recognizing the benefits of the TAPUR Study’s simple design and practical implementation. With ASCO’s help, the TAPUR Study model is being emulated and expanded to other countries in a growing international collaboration to help patients with cancer around the world.
“The ASCO Board recognized not only the vast potential for such a trial, but the urgent need for such a trial in the current era of genomically defined tumors, rather than ‘organ-defined’ tumors,” said TAPUR Study principal investigator Richard L. Schilsky, MD, FACP, FSCT, FASCO. “We were thrilled to have their full support from the beginning, but never dreamed at the time just how far this trial would go.”
Known as a basket trial, the TAPUR Study is designed to enroll patients with tumors that have specific genomic alterations and treat them with molecularly targeted cancer drugs already approved for other indications in hopes these patients may benefit. Nearly all patients who participate in the TAPUR Study have advanced solid tumors that have not responded to standard care or had limited options to begin with. Each patient is enrolled in a cohort based on the tumor type, the genomic alteration of the tumor, and the treatment targeted for that specific alteration.
Launched in 2016, today, the TAPUR Study has more than 2,100 patients enrolled at more than 130 cancer centers, hospitals, and oncology practices participating in the U.S. Additional sites will be added later this year, bringing the size of the TAPUR Study network to approximately 180 clinical sites located in more than 24 states.
“TAPUR is a major step in transitioning from an outdated model of cancer care, in which therapies are chosen only on the basis of where in the body the cancer started (e.g., breast, pancreas, skin, etc.), to focusing on the molecular changes that initiate and drive the growth of an individual’s cancer. The results so far have begun to help us understand which treatments can actually work for specific molecular/DNA variants in tumors and which don’t,” said Timothy L. Cannon, MD, chair of the TAPUR Study Steering Group. Dr. Cannon is the clinical director and moderator of Inova Schar’s Molecular Tumor Board in Fairfax, VA.
Unlike many similar trials, the TAPUR Study is designed to limit the administrative burden on the physicians who make it possible for patients to participate, to reduce and simplify data entry, and to streamline the paperwork required for regulatory and adverse event reporting.
Pharmaceutical companies have been very supportive of ASCO’s trial from the start. Drugs used in the TAPUR Study are provided at no cost by participating drug manufacturers eager to learn how their treatments work in other types of cancers. Nine pharmaceutical companies are currently providing a total of 22 drugs for the study, which yield 18 therapies (some drugs are used in combination). Seagen, Inc., is TAPUR’s latest pharmaceutical company collaborator.
Data on clinical outcomes from each cohort are being collected, analyzed, and reported on a regular basis, which may help to identify potential uses for these drugs outside of their FDA-approved indications. In the case of negative clinical outcomes, the cohorts are closed, but in the case of positive clinical outcomes, the cohorts are expanded so additional patients can be treated.
Positive findings from cohorts in uterine cancer, head and neck cancer, and soft tissue sarcoma are being presented at the 2021 ASCO Annual Meeting taking place June 4-8:
“Pertuzumab plus trastuzumab (P+T) in patients (Pts) with uterine cancer (UC) with ERBB2 or ERBB3 amplification, overexpression or mutation: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study” by Ali-Ahmad, et al., found that treatment with pertuzumab and trastuzumab had anti-tumor activity in heavily pretreated patients with uterine cancer and ERBB2 amplification or certain ERBB2 mutations. Abstract 5508 (oral presentation)
“Palbociclib (P) in patients (pts) with head and neck cancer (HNC) with CDKN2A loss or mutation: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study” Pisick, et al., found that palbociclib monotherapy demonstrated modest anti-tumor activity in heavily pretreated patients with head and neck cancer with CDKN2A loss or mutation. Abstract 6043 (poster)
“Palbociclib (P) in patients (pts) with soft tissue sarcoma (STS) with CDK4 amplification: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study” by Schuetze, et al., found that palbociclib monotherapy demonstrated anti-tumor activity in heavily pretreated patients soft tissue sarcoma and CDK4 amplification. Abstract 11565 (poster)
These and other previously reported results clearly show that the TAPUR Study is achieving its goals, according to Dr. Schilsky: “To some extent, as long as we generate information that is fairly definitive, whether positive or negative, we think we’re achieving some success,” he explained. “A negative result is informative if it discourages physicians from prescribing a drug that’s not likely to work outside of its approved indication. With a positive signal, I think success would be that the results are sufficiently persuasive that they are incorporated in clinical practice guidelines or compendia. And the ultimate, of course, would be if the company that owns the drug could use the data to seek a label expansion from the FDA because the data would be sufficiently strong to support its use in a new indication.”
ASCO is actively collaborating with researchers in other countries to help them replicate the trial outside the U.S., providing forms and study design guidance.
The Canadian Cancer Trials Group is conducting the Canadian Profiling and Targeted Agent Utilization Trial (CAPTUR; ClinicalTrials.gov identifier: NCT02693535), based on the design of the TAPUR Study. Like TAPUR, the CAPTUR trial is testing the activity of a number of commercially available targeted agents in patients who have undergone tumor genomic profiling and have genetic mutations that may respond to particular targeted drugs. The plan was always to merge data from CAPTUR with that from the TAPUR Study, but many issues had to be worked out to do so.
“Coordinating trial design is relatively easy,” said Janet Dancey, MD, FRCPC, director of the Canadian Cancer Trials Group and a professor in the Department of Oncology at Queen’s University in Ontario. “What is more complicated and needs to be improved is the ability to easily coordinate participation among countries. Each country has to address regulatory and drug access issues, as well as analyses of samples. We also have to reach consensus on statistical design, primary endpoints, and specific data for sharing.”
Dr. Dancey noted that CAPTUR was possible because the Canadian cancer community supported it—patients, clinicians, genomic scientists, molecular pathologists, and pharmaceutical companies. “For the Canadian Cancer Trial Group Operations and Statistical Centre at Queen’s University, it was a challenge to operationalize given the number of drugs, genomic variants, and potential large number of cohorts,” she said. “Everyone has enthusiastically worked hard to address these issues.”
ASCO also is working with researchers conducting the Netherlands Cancer Institute-sponsored Drug Rediscovery Protocol (DRUP; ClinicalTrials.gov identifier: NCT02925234), a similar basket trial launched in 2016. DRUP shares the same endpoints as the TAPUR Study: seeking a response to a particular drug in at least 30% of the cohort of patients who have exhausted standard therapies and have tumors with genomic variants for which no approved treatments are available.
In the September 2019 issue of Nature, Dutch researchers published an article that provided an overview of the DRUP trial including some the findings to date. The article reported that in 34% of the 215 patients treated, the cancer had an objective response to a drug or had not progressed by the 16-week mark, and the median duration of clinical benefit was 9 months.
The researchers behind TAPUR, CAPTUR, and DRUP are now collaborating to further new discoveries/progress as quickly as possible. The CAPTUR trial is beginning to analyze cohorts and soon will be proposing cohorts that could be shared with TAPUR and DRUP colleagues, as well as seeking to add therapies, trial sites, and laboratories.
“Together we have developed a data-sharing protocol that will specify how we will ultimately combine the data from those three studies, which will give us many more patients and a much more robust analysis of rare cohorts,” Dr. Schilsky said.
Studies similar to TAPUR have recently been launched in Denmark (Pro-Target; Clinicaltrials.gov identifier: NCT04341181) and South Korea, and discussions are underway with colleagues in Australia to develop a similar study there.
“We have a sense that we are on the cusp of important discoveries, and the collective excitement we share is palpable,” said Dr. Schilsky. “The next step will be to begin to combine targeted therapies, something not typically done in single-sponsor clinical trials, but which this type of trial will make possible, for the benefit of all.”
Ultimately, it’s all about improving care for patients with cancer. Dr. Cannon says of his experience as a TAPUR site representative for Inova, “The most rewarding part of being part of TAPUR has been seeing patients, who were not benefitting from chemotherapy, be able to transition to effective targeted therapies. In some cases, they have been able to stay on these therapies for years.”