FDA Grants Orphan Drug Status to PD-1 Blocker Toripalimab for Esophageal Cancer

The FDA has granted an orphan drug designation to toripalimab for the treatment of esophageal cancer, according to a press release by Coherus Biosciences, Inc.

Toripalimab is an anti-PD-1 monoclonal antibody that is meant to block PD-1 from interaction with PD-L1 and PD-L2. The blocking of these 2 ligands is thought to boost the immune system’s ability to kill tumor cells. In addition to esophageal cancer, it is being looked at in lung, nasopharynx, stomach, bladder, breast, liver, kidney, and skin cancers.

The agent was evaluated in combination with cisplatin chemotherapy during the phase 3 JUPITER06 trial (NCT03829969). It has an actual enrollment of 514 participants. The primary end points are progression-free survival (PFS) and overall survival (OS). Secondary end points include overall response rate (ORR), disease control rate (DCR), duration of response (DOR), time to response (TTR), and patient-reported outcomes.

During the study, patients were randomized 1:1 to receive a combination of toripalimab and cisplatin or a placebo and cisplatin.

A total of 514 patients were included in the analysis, 257 in each arm. At a follow up of 7.4 months in the experimental arm and 7.3 months in the control arm, OS was found to be significantly improved with toripalimab. In the experimental arm, the OS was 17 months versus 11 months in the control (HR,0.58; 95% CI, 0.43-0.78; P =.00037).

Additionally, the one-year OS rate in the control arm was 43.7% versus 66% in the experimental arm. PFS was also found to be significantly improved in the experimental arm over the control arm (HR, 0.58; 95% CI, 0.46-0.74; P <.00001).

In terms of safety, grade 3 or higher adverse events (AEs) occurred in the 73.2% of patients in the experimental arm and 70% of patients in the control arm. AEs led to discontinuation in 11.7% of patients in the experimental arm and 6.2% of patients in the control arm. Immune-related AEs occurred in37% of patients in the control arm and 26.5% of patients in the experimental arm.

In order to participate in JUPITER06, patients must be between 18 and 70 years of age, have an ECOG score of 0 or 1, a life expectancy longer than 3 months, at least one measurable lesion, and good organ function. Patients with active or untreated central nervous system metastasis, cardiovascular disease, or pulmonary tuberculosis are not eligible to participate.

“Esophageal squamous cell carcinoma is an aggressive cancer, and patients need new and better treatment options. We plan to work closely with our partner, Junshi Biosciences, to submit a [biologics license application] supplement for toripalimab for this indication in 2022,” said Denny Lanfear, CEO of Coherus, in a press release.

_REFERENCES:

_{1.Coherus and Junshi Biosciences announce toripalimab granted orphan drug designation in the united states for esophageal cancer. News release. Coherus. November 15, 2021. Accessed November 16, 2021. https://bit.ly/3qITmCc}

_{2.Toripalimab or placebo with paclitaxel and cisplatin in esophageal squamous cell carcinoma (JUPITER06). ClinicalTrials.gov. Accessed November 16, 2021. https://bit.ly/3FiGEOE}

_{3.JUPITER-06: A randomized, double-blind, phase III study of toripalimab versus placebo in combination with first-line chemotherapy for treatment naive advanced or metastatic esophageal squamous cell carcinoma (ESCC). Ann. Oncol. 2021;32(5):1041. doi: 10.1016/j.annonc.2021.08.1482}