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Janssen Hoping to Bring Tissue-Agnostic Data on Balversa to Regulators Next Year


NEW YORK – A tumor-agnostic trial of Janssen's Balversa (erdafitinib) in patients with advanced FGFR-altered solid tumors showed efficacy across a range of tumor types, bolstering the drugmaker's plans for a potential regulatory filing next year.

The Phase II study, called RAGNAR, was Janssen's first tumor-agnostic trial and the first tissue-agnostic study in patients with FGFR alterations to report results. In the trial, Balversa demonstrated a 29.2 percent response rate with responses seen across 14 tumor types, according to the results presented at the American Society of Clinical Oncology's annual meeting earlier this month.

Balversa was approved in the US in 2019 for the treatment of patients with advanced or metastatic bladder cancer harboring FGFR2 or FGFR3 alterations, along with a companion diagnostic from Qiagen to identify eligible patients with these biomarkers.

The initial data readout from RAGNAR looks promising for Balversa's tissue-agnostic potential. And the drugmaker expects that data readouts later this year will likely support regulatory submissions to the US Food and Drug Administration and the European Medicines Agency, according to Craig Tendler, Janssen's global head of late clinical development, diagnostics, and medical affairs for hematology and oncology.

According to Tendler, Janssen is planning to begin discussions with regulators for the first half of 2023.

"We're assuming [the final analysis] is going to be consistent with what was presented at ASCO," Tendler said. "Our plan is to share that data with health authorities and then have discussions about a pathway to approval both at the FDA and the EMA."

The RAGNAR results presented at ASCO by Yohann Loriot, a medical oncologist at the Gustave Roussy Cancer Institute, included data from 178 patients with various tumor types. The most common tumor type enrolled in the trial was cholangiocarcinoma (17 percent), followed by high-grade glioma, breast cancer, pancreatic cancer, non-small cell lung cancer, and cancer of unknown primary. In total, the study included more than 18 tumor types harboring FGFR1-3 alterations or fusions but excluded patients with bladder cancer due to other ongoing studies of Balversa in bladder cancer.

"Most of these tumors characteristically have a low incidence of FGFR alterations. In some of these tumor types, the incidence of FGFR mutations and fusions are in the order of single digits, 1 percent to 3 percent," Tendler said. "This is a group of patients who would normally be treated with unselected therapy, but the results here really make the argument much clearer that therapy selected on the basis of the molecular profiling, in this case alterations of FGFR, can be very effective."

Across all patients, the response rate by independent review committee was 29.2 percent, the clinical benefit rate was 48.9 percent, and two-thirds of patients had a reduction in tumor burden. The median duration of response was 7.1 months, progression-free survival was 5.2 months, and overall survival was 10.9 months. The response rates for patients with FGFR mutations and FGFR fusions were also similar, 26.8 percent and 27 percent, respectively.

Patients with historically difficult-to-treat cancers also responded to Balversa. For example, 100 percent of the five salivary gland cancer patients in the trial responded; 31 percent of pancreatic cancer patients had a response; and 21 percent of glioblastoma patients saw reductions in tumor size, Loriot said.

"There was no single tumor type that predominated the response profile," he said. "Confirmed responses were observed in 14 distinct tumor types [but] no responses were observed to date in patients with colorectal, gastric, or cervical cancer."

The Phase II trial that led to Balversa's accelerated approval in FGFR-altered bladder cancer demonstrated a response rate of 40 percent, Loriot said. Janssen is also exploring the drug in FGFR-altered cholangiocarcinoma in a Phase II study, and recent results from that trial showed a response rate of 41 percent, he added.

In a discussion of the RAGNAR data at ASCO, Philippe Bedard, a clinician investigator at the Princess Margaret Cancer Centre, said there are several ongoing tumor-agnostic basket trials in FGFR-altered solid tumors.

While Balversa is the only drug approved for FGFR-altered bladder cancer, the drug has competitors in other areas. Incyte's Pemazyre (pemigatinib) and QED Therapeutics' and Helsinn's Truseltiq (infigratinib) are both approved in the US to treat FGFR2 fusion-positive cholangiocarcinoma.

Both Pemazyre and Truseltiq have been explored in tumor-agnostic studies, along with Bayer's rogaratinib and Taiho Oncology's futibatinib.

"The activity reported with RAGNAR is at the upper end, if not the highest activity that’s been seen [among these basket trials] in patients with FGFR alterations across solid tumors," Bedard said.

However, he noted there are unresolved questions about the tumor-agnostic activity of Balversa and other FGFR targeted therapies including activity in earlier lines of therapy and potential mechanisms of resistance to these drugs by tumor types or different co-occurring mutations.

Tendler noted that Janssen is hoping to explore the drug in earlier lines of therapy in bladder cancer in the future. For now, the focus is on the confirmatory trials of Balversa in advanced bladder cancer, including studies comparing the drug with chemotherapy and with immunotherapy, and the ongoing tumor-agnostic RAGNAR study.

One ongoing challenge with Balversa, and targeted therapies generally, is identifying patients for treatment. A recent study from the University of Pennsylvania showed only 45 percent of bladder cancer patients in Flatiron Health's real-world database had been tested for FGFR alterations. That same study explored how many FGFR-positive bladder cancer patients went on to receive Balversa, the only approved drug in the space, and found only 42.3 percent of those with identified mutations went on to receive the targeted therapy.

"Our hope is as we generate more of these compelling results, this will also be the impetus … for making molecular profiling more accessible, more available for these patients," Tendler said. "We supported quite a bit of the molecular profiling screening for this study. In the real world that has to be something that we work to achieve as well, because obviously without this information, these patients would never get treated with erdafitinib."