The FDA has approved toripalimab, with cisplatin and gemcitabine, and as a monotherapy, to treat adults with nasopharyngeal carcinoma.
The FDA has approved toripalimab-tpzi (Loqtorzi) to treat adult patients with nasopharyngeal carcinoma. The agent is approved in combination with cisplatin and gemcitabine to treat metastatic or recurrent, locally advanced disease. It has also been approved as a single agent for patients with recurrent unresectable or metastatic disease who have already received a platinum-containing chemotherapy.1
“Today’s FDA approval of [toripalimab] is very encouraging for those living with [nasopharyngeal carcinoma] who currently have very limited treatment options and are in need of new therapies to treat this aggressive and life-threatening form of cancer,” Jong Chul Park, MD, assistant professor at Harvard Medical School and attending physician at the Center for Head and Neck Cancers at Massachusetts General Hospital Cancer Center, said in a press release.2
“[Toripalimab] is a new treatment option that has demonstrated the ability to significantly improve PFS [progression-free survival] and OS [overall survival] and should quickly emerge as the new standard of care when used in combination with chemotherapy,” Park added.
Findings from the phase 3 JUPITER-02 trial (NCT03581786) supported the combination’s approval. This was a randomized, multicenter, single region, double-blind, placebo-controlled trial and included 289 chemotherapy-naïve patients with metastatic or recurrent, locally advanced nasopharyngeal carcinoma.1
Patients in this trial were randomly assigned 1:1 to receive either toripalimab with cisplatin and gemcitabine, followed by toripalimab, or placebo with cisplatin and gemcitabine, followed by placebo.
PFS, assessed by Blinded Independent Review Committee (BICR), served as the trial’s primary end point. OS was a secondary end point. In this trial, patients who received the toripalimab combination achieved a median PFS of 11.7 months, compared with 8.0 months in patients receiving placebo plus chemotherapy (HR, 0.52; 95% CI, 0.36-0.74; P = .0003). Investigators also observed a statistically significant OS improvement with toripalimab (HR, 0.63; 95% CI, 0.45-0.89; P = .0083). The median OS was not reached with toripalimab and 33.7 months with placebo.
Findings from the phase 2 POLARIS-02 trial (NCT02915432) backed the single-agent approval. This was an open-label, multicenter, single country, multicohort trial which included 172 patients with unresectable or metastatic disease. All participants had received prior platinum-based chemotherapy or had experienced disease progression within 6 months of completing their platinum-based chemotherapy—which could have been neoadjuvant, adjuvant, or definitive chemoradiation.
Overall response rate (ORR) served as the primary end points in POLARIS-02 and were assessed via BICR. The ORR was 21% (95% CI, 15%-28%) and the median DOR was 14.9 months (95% CI, 10.3-not estimable) with toripalimab monotherapy.
The most common adverse events (AEs) associated with toripalimab plus chemotherapy are nausea, vomiting, decreased appetite, constipation, hypothyroidism, rash, pyrexia, diarrhea, peripheral neuropathy, cough, musculoskeletal pain, upper respiratory infection, insomnia, dizziness, and malaise. For those receiving single-agent therapy, the most common AEs are fatigue, hypothyroidism, and musculoskeletal pain.
Of note, there is a risk of immune-mediated AEs with toripalimab, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, and skin adverse reactions.
The recommended dose for the combination therapy is 240 mg every 3 weeks. Patients can continue treatment until disease progression, unacceptable toxicity, or when they reach the 24-month mark. For single-agent toripalimab, the recommended dose is 3 mg/kg every 2 weeks until disease progression of unacceptable toxicity.
Coherus is the manufacturer of toripalimab, and they have stated that they are committed to ensuring that eligible patients can received PD-immunotherapy with less financial burden. In a press release, they stated that they offer reimbursement support, patient support, and access support.2
“The impressive results from JUPITER-02 and POLARIS-02 have provided conclusive evidence that establishes toripalimab, in combination with chemotherapy or as monotherapy, as the standard therapy for advanced [nasopharyngeal carcinoma],” Ruihua Xu, professor at Sun Yat-sen University Cancer Center, and principal investigator of JUPITER-02 and POLARIS-02, added. “We hope that this promising therapy will close the treatment gap for international [nasopharyngeal carcinoma] patients struggling to find effective therapies, bringing them renewed hope for better survival.”