Dividing human cancer cells, 3D rendering.
The Food and Drug Administration’s accelerated approval last year for Merck & Co.’s immunotherapy drug Keytruda based on whether a tumor exhibits certain genetic abnormalities rather than which organ the tumor affects has created a proof of concept for similar drug approvals moving forward.
That’s the main takeaway from a new white paper from healthcare consultancy Trinity Partners on so-called “basket trials.” These are clinical studies in which patients are enrolled based on whether they exhibit mutations rather than specific tumor types.
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The report, issued Tuesday, identified 37 studies through the online database ClinicalTrials.gov that are testing drugs in indications driven by biomarkers instead of in tumors that affect specific tissues. Of these, two were classified as registration-directed, namely Loxo Oncology’s Phase II study of LOXO-101 (larotrectinib) in tumors with NTRK fusions and Ignyta’s Phase II study of RXDX-101 (entrectinib) in patients with tumors harboring NTRK or ALK fusions. Another nine studies were deemed potentially registrational, while the remainder were judged to be still in the exploratory stage. Loxo announced in March that it had completed a rolling submission for FDA approval of LOXO-101 while, Roche completed its acquisition of Ignyta in February.
Keytruda became the first drug to carry a biomarker-based label with its accelerated approval last May for microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumors.
A number of factors have spurred the move toward basket studies, such as the growth of personalized medicine and next-generation sequencing, enabling oncologists and researchers to better understand different mutations and how patients might respond to treatments, said Trinity Partners Principal Jillian Godfrey Scaife in an interview.
“Understanding genetics and biomarkers could be a new approach to treatment in oncology,” Scaife said in a phone interview.
According to a list included in the appendix of the white paper, the majority of therapies under development are by public companies, including Loxo – which is partnered with Bayer on this study – Pfizer, AbbVie, Novartis, and others.
Meanwhile, Watertown, Massachusetts-based Tarveda Therapeutics, which is developing PEN-221 to target tumors expressing SSTR2, scored a $30 million Series D round led by Versant Ventures. And in May of last year, San Diego, California-based TP therapeutics – whose TP-0005 targets ALK, ROS1, and NTRK alterations – closed a $45 million Series C round led by Lilly Asia Ventures, OrbiMed Advisors and S.R. One, according to a press release.
Still, while genetic testing has driven the interest in biomarker-driven studies, it could at the same time be a hurdle for tissue-agnostic drugs, Scaife said. Right now, NGS is not widely adopted, and if a mutation is not included in a panel, then it will be unknown if a patient carries it. Another question is how payers might approach tissue-agnostic therapies, she said. Indeed, the report states, how payers will incorporate tissue-agnostic therapies into their formularies is an unanswered question, and it appears likely they will evaluate therapies based on data specific to tumor sites within the context of tissue-agnostic data packages.
A related issue is the National Comprehensive Cancer Network Guidelines, which are primarily outlined by the affected organ system. It is possible, Scaife said, that the NCCN Guidelines could move toward a more tissue-agnostic approach. The NCCN Guidelines outline treatment modalities for various cancers and are frequently used by payers for reimbursement decisions. Throughout 2017, the NCCN committees voted to issue recommendations for Keytruda in MSI-H and dMMR based on individual solid tumors rather than wholesale, per the drug’s label, organization records show.
Abstracts from next month’s ASCO annual meeting offered a taste of more biomarker-driven data to come. Loxo will present an update on LOXO-292, which targets fusions and mutations of the gene RET, while there will also be early data for Ignyta’s drug in children and adolescents. Blueprint Medicines will not have data on its RET inhibitor, BLU-667, but it did present data on the drug at the American Association for Cancer Research’s annual meeting last month. After abstracts dropped last Wednesday evening, Loxo shares were up 20 percent by the time markets closed Thursday, on data showing 69 percent of 32 patients responded to treatment, though 11 patients’ responses were still pending confirmation at the time.
Photo: nopparit, Getty Images
