Drug manufacturers Coherus and Junshi Biosciences announced today that the US Food and Drug Administration (FDA) has issued a complete response letter for the biologics license application (BLA) for toripalimab for the treatment of advanced recurrent or metastatic nasopharyngeal carcinoma (NPC).
The complete response letter requested a “quality process change” that the drug companies say “is readily addressable,” according to a press release, which did not provide details on this quality process change.
Coherus and Junshi Biosciences plan to meet with the FDA and resubmit their BLA by mid-summer 2022. The FDA said the review timeline for the resubmission would take about 6 months because the FDA must complete onsite inspections in China. Those inspections have been delayed by travel restrictions related to the pandemic.
The FDA had granted toripalimab BLA priority review last November. The BLA covered two indications for the immune checkpoint inhibitor: first-line treatment in combination with gemcitabine and cisplatin for advanced recurrent or metastatic NPC, as well as second-line treatment as monotherapy for recurrent or metastatic NPC after progression on platinum-containing chemotherapy.
If approved, toripalimab would be the first immunotherapy in the US for the indication.
“We believe toripalimab addresses an important unmet need for patients with NPC,” Denny Lanfear, CEO of Coherus, said in a press release. “We will continue to work closely with our partner, Junshi Biosciences, to facilitate the completion of the FDA’s review of the toripalimab BLA.”
In previous Medscape Medical News coverage, oncologist Jared Weis, MD, a head and neck cancer specialist at the University of North Carolina at Chapel Hill, said that approving toripalimab “would change [first-line] standard of care to the triplet regimen.”
The first-line indication is based on the company’s phase 3 JUPITER-02 trial, in which toripalimab was added to gemcitabine and cisplatin. In the JUPITER-02 trial, researchers randomly assigned 146 previously untreated patients to receive toripalimab and 143 to receive placebo, both on the gemcitabine and cisplatin background. Patients received either toripalimab 240 mg or placebo alongside gemcitabine and cisplatin every 3 weeks for up to six cycles, followed by toripalimab or placebo maintenance every 3 weeks until disease progression, intolerable toxicity, or 2 years of treatment.
Median progression-free survival (PFS) was 11.7 months with toripalimab, vs 8 months with placebo. The results, as of February 18, 2021, showed that overall survival (OS) favored toripalimab, with 25 deaths vs 39 in the placebo group, a 40% risk reduction. Median duration of response with toripalimab was 10 months, vs 5.7 months with placebo.
Adverse events leading to discontinuation occurred in 7.5% of the study group, vs 4.9% on placebo. Discontinuations were driven mostly by immune-related adverse events, such as hypothyroidism. These events were more common with toripalimab (39.7% vs 18.9%), as were grade 3 or worse immune-related adverse events (7.5% vs 0.7%).
Results for the second-line indication come from the POLARIS-02 trial, an open-label phase 2 investigation that involved 190 patients with recurrent or metastatic NPC refractory to standard chemotherapy. Treatment consisted of toripalimab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity.
The overall response rate was 20.5%. The median duration of response was 12.8 months, with a median PFS of 1.9 months and a median OS of 17.4 months. Among the 92 patients in whom at least two lines of systemic chemotherapy had failed, the overall response rate was slightly higher — 23.9%. An early drop in plasma Epstein-Barr virus DNA copy number heralded a favorable response.
Toripalimab was first approved in China in December 2018 for second-line treatment of advanced melanoma. It has since received approval for NPC and other indications there.
Weiss has disclosed no relevant financial relationships.
M. Alexander Otto is a physician assistant with a master’s degree in medical science. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape and is an MIT Knight Science Journalism fellow. Email: [email protected].
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