After patient death, FDA slaps clinical hold on Iovance’s lung cancer cell therapy trial

The FDA has hit Iovance Biotherapeutics’ cell therapy trial with a clinical hold after a patient with non-small cell lung cancer (NSCLC) died in a case that may be related to the study. 

The federal agency implemented the hold Dec. 22 after a grade 5 adverse event (AE)—the most serious form of AE that signifies a fatality—was reported, according to a Dec. 27 release from Iovance. The patient death is potentially related to the non-myeloablative lymphodepletion pre-conditioning regimen, Iovance added in its statement. 

The hold centers around LN-145, one of the California biotech’s tumor-infiltrating lymphocyte (TIL) therapies being assessed in a phase 2 trial called IOV-LUN-202 for patients who have progressed on or after chemotherapy and anti-PD-1 therapy for advanced NSCLC.

The clinical hold means Iovance will halt both trial enrollment and the LN-145 TIL treatment regimen for new patients. Trial participants who have already received LN-145 will continue to be monitored, while patients who have already undergone tumor resection will keep receiving the TIL treatment regimen with added precautions and risk mitigation, according to Iovance.

So far, more than 100 patients with lung cancer have received the investigational treatment. In July, Iovance shared preliminary data from the single-arm trial and said the data “may be acceptable” to secure an accelerated approval for LN-145.  

The early analysis included data from 23 patients and found a 26.1% objective response rate—or one complete and five partial responses—plus a disease control rate of 82.6%. An updated analysis in November showed additional ongoing responses and a response duration greater than six months for 71% of confirmed responders, according to Iovance.

Previously reported treatment-emergent AEs have been consistent with known AE profiles of non-myeloablative lymphodepletion and interleukin-2, the biotech said.

“We will work with the FDA to safely resume enrollment in the IOV-LUN-202 trial as soon as possible,” Iovance Chief Medical Officer Friedrich Graf Finckenstein, M.D., said in the Dec. 27 release.

The company’s stock tumbled 20% Wednesday, Dec. 27 morning after the hold was announced, dropping from $8.9 per share at market close on Tuesday to $7.05 the next day. However, the stock has somewhat recovered since then, rising back up to $8.26 mid-day Friday. Dec. 29.

The IOV-LUN-202 hold doesn’t affect any other Iovance trials, including the company’s lead asset lifileucel, which is currently under FDA review for possible approval in advanced melanoma. With a decision expected by or before Feb. 24, lifileucel has the potential to become the first one-time cell therapy for a solid tumor cancer to hit the markets.