FDA Grants Orphan Drug Designation to Toripalimab for Esophageal Cancer

FDA

The FDA has granted an orphan drug designation to toripalimab for the treatment of patients with esophageal cancer, according to an announcement from Coherus BioSciences, Inc. and Shanghai Junshi Biosciences Co., Ltd.¹

The decision follows the data read out from the phase 3 JUPITER-06 trial (NCT03829969), which showed that the addition of toripalimab to platinum-based chemotherapy significantly improved survival vs chemotherapy alone in patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC), irrespective of PD-L1 expression.²

The median progression-free survival (PFS) with toripalimab (n = 257) was 5.7 months (95% CI, 5.6-7.0) vs 5.5 months (95% CI, 5.2-5.6) with placebo (n = 257), translating to a 42% reduction in the risk of progression (HR, 0.58; 95% CI, 0.461-0.738; P < .00001). The median overall survival (OS) in the investigative arm was 17.0 months (95% CI, 14.0–not estimable [NE]) vs 11.0 months (95% CI, 10.4-12.6) in the control arm (HR, 0.58; 95% CI, 0.425-0.783; P = .00036).

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

JUPITER-06 enrolled a total of 514 patients with treatment-naïve advanced or metastatic ESCC who had not previously received chemotherapy. Participants were randomized 1:1 to receive either toripalimab at 240 mg or placebo in combination with paclitaxel at 175 mg/m2 and cisplatin at 75 mg/m2 once every 3 weeks for up to 6 treatment cycles; this was followed by maintenance treatment with either toripalimab or placebo.

Treatment was administered until disease progression, unacceptable toxicity, withdrawn consent/investigator decision, or up until 2 years. Stratification factors comprised previous radiation (yes vs no) and ECOG performance status (0 vs 1).

The co-primary end points of the trial were PFS per independent central review and RECIST v1.1 criteria and overall survival. Key secondary end points comprised investigator-assessed PFS, objective response rate, duration of response, and disease control rate. Investigators also evaluated 1- and 2-year PFS and OS rates, safety, and health-related quality of life.

Baseline characteristics were found to be well balanced between the arms. In the investigative arm, the median age was 63.0 years (range, 20-75), 74.3% had an ECOG performance status of 1, and 80.2% had metastatic disease. In the control arm, the median age was 62.0 years (range, 40-74), 74.7% had an ECOG performance status of 1, and 77.0% had metastatic disease. Moreover, 19.5% of those who received toripalimab had recurrent or unresectable disease at baseline vs 23.0% of those who were given placebo.

Regarding PD-L1 expression, the majority of patients had a combined positive score (CPS) of 1 or higher. In the toripalimab arm, 16.7% had a CPS less than 1, 78.2% had a score of at least 1, 50.2% had a score of less than 10, and 44.7% had a score of at least 10. In the control arm, these rates were 17.1%, 77.8%, 57.2%, and 37.7%, respectively. CPS information was not available for 5.1% of those on each treatment arm.

Additional data presented during the 2021 ESMO Congress demonstrated that the 1-year PFS rates with toripalimab or placebo were 27.8% (95% CI, 20.4%-35.8%) and 6.1% (95% CI, 2.2%-12.6%), respectively. Moreover, the 1-year OS rates in the investigative and control arms were 66.0% (95% CI, 57.5%-73.2%) and 43.7% (95% CI, 34.4%-52.6%), respectively; these rates at 2 years were NE (95% CI, NE–NE) and 17.5% (95% CI, 8.7%-28.9%), respectively.

In the cohort of patients with high PD-L1 expression, defined as a CPS of 1 or higher, the median PFS with toripalimab/chemotherapy (n = 201) was 5.7 months vs 5.5 months with chemotherapy alone (n = 200; HR, 0.58; 95% CI, 0.444-0.751). The median OS in this subset was 15.2 months in the investigative arm and 10.9 months in the control arm (HR, 0.61; 95% CI, 0.435-0.870).

In the cohort of patients with low PD-L1 expression, defined as a CPS of less than 1, the median PFS in the investigative (n = 43) and control (n = 44) arms was 5.7 months and 5.6 months, respectively (HR, 0.66; 95% CI, 0.370-1.189). The median OS in this subset was NE in the investigative arm and 11.6 months in the control arm (HR, 0.61; 95% CI, 0.297-1.247).

Regarding safety, any-grade adverse effects (AEs) were experienced by 97.3% of patients in each treatment arm. Grade 3 or higher toxicities were reported in 64.6% of those who received toripalimab vs 56.0% in those who just received chemotherapy. Moreover, 3.5% and 3.1% of patients in the investigative and control arms, respectively, reported all-grade infusion-related reactions; 2 of these patients who received toripalimab had a grade 3 or higher event.

Moreover, 3.5% of those who received toripalimab plus chemotherapy experienced any-grade toxicities that resulted in discontinuation vs 0.8% of those who received chemotherapy alone. One patient in the investigative arm experienced a fatal AE vs 3 in the control arm.

The most frequent toxicities were anemia, leukopenia, neutropenia, nausea, peripheral neuropathy, fatigue, decreased appetite, alopecia, and vomiting.

In July 2021, the National Medical Products Administration of China accepted a supplemental new drug application based on findings from JUPITER-06.³ More recently, in November 2021, the FDA accepted for review a biologics license application for toripalimab plus gemcitabine and cisplatin in the first-line treatment of patients with advanced recurrent or metastatic nasopharyngeal carcinoma, and for use as a single agent in the second- or later-line treatment of patients with recurrent or metastatic nasopharyngeal carcinoma after platinum-containing chemotherapy.⁴

References

1. Coherus and Junshi Biosciences announce toripalimab granted orphan drug designation in the United States for esophageal cancer. News release. Coherus Biosciences, Inc. and Shanghai Junshi Biosciences Co., Ltd; November 15, 2021. Accessed November 16, 2021. https://bit.ly/3DpLNnt
2. Xu R-H, Wang F, Cui C, et al. 1373 MO 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(suppl 5):S1041. doi:10.1016/j.annonc.2021.08.1482
3. Junshi Biosciences announces acceptance by NMPA of supplemental new drug application for toripalimab plus chemotherapy as first-line treatment for advanced or metastatic esophageal squamous cell carcinoma. News release. Junshi Biosciences; July 31, 2021. Accessed November 16, 2021. https://bit.ly/3CjgxFJ
4. Coherus and Junshi Biosciences announce FDA acceptance of BLA filing for toripalimab for treatment of nasopharyngeal carcinoma. News release. Coherus BioSciences, Inc. and Shanghai Junshi Biosciences Co., Ltd.; November 1, 2021. Accessed November 16, 2021. https://bit.ly/3CwoLeh