EU to Approve Toripalimab for Advanced Head & Neck, & Zolbetuximab in GEJ cancer

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Toripalimab-tpzi for Nasopharyngeal Carcinoma (NPC)

Toripalimab-tpzi, in combination with cisplatin and gemcitabine, has been recommended for first-line treatment of adult patients with NPC that is recurrent, not amenable to surgery or radiotherapy, or metastatic. This recommendation is grounded in data from the phase 3 JUPITER-02 trial, an international, multicenter, randomized, double-blind study that enrolled patients with recurrent or metastatic NPC who had not received prior systemic chemotherapy.

Results showed that patients treated with toripalimab plus chemotherapy experienced a median progression-free survival (PFS) of 21.4 months, significantly longer than the 8.2 months observed in the placebo plus chemotherapy group. The 1- and 2-year PFS rates were notably higher in the toripalimab group at 59.0% and 44.8%, compared to 32.9% and 25.4% in the placebo group.

Both treatment and placebo groups reported similar rates of any-grade treatment-emergent adverse effects (TEAEs) at 100%. However, the toripalimab group had higher rates of adverse effects leading to treatment discontinuation (11.6% vs. 4.9%) and immune-related adverse effects (54.1% vs. 21.7%), including a higher incidence of grade 3 or higher immune-related adverse effects (9.6% vs. 1.4%). Rates of grade 3 or higher TEAEs, fatal TEAEs, serious adverse events, and infusion reactions were comparable between the two groups.

Toripalimab for Esophageal Squamous Cell Carcinoma (ESCC)

The CHMP has also recommended toripalimab in combination with cisplatin and paclitaxel for first-line treatment of adult patients with unresectable advanced, recurrent, or metastatic ESCC. This recommendation is supported by findings from the phase 3 JUPITER-06 trial.

In the JUPITER-06 trial, patients treated with toripalimab plus chemotherapy achieved a median PFS of 5.7 months, compared to 5.5 months in the placebo group. The median overall survival (OS) was 17 months for the toripalimab group, significantly longer than the 11 months observed in the placebo group.

Safety data revealed that 99.2% of patients in both the toripalimab and placebo groups experienced at least one treatment-emergent adverse event (TEAE). Severe (grade 3 or higher) TEAEs occurred in 73.2% of the toripalimab group and 70.0% of the placebo group. Fatal TEAEs were reported in 8.2% of patients in both groups, but fatal adverse events related to treatment were lower in the toripalimab group (0.4%) compared to the placebo group (1.2%).

Zolbetuximab for Gastric and Gastroesophageal Junction (GEJ) Adenocarcinoma

Additionally, the CHMP has recommended the approval of zolbetuximab combined with fluoropyrimidine- and platinum-containing chemotherapy for the treatment of locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma with CLDN18.2 positivity. This recommendation is based on the results of the phase 3 SPOTLIGHT and GLOW trials.

In the SPOTLIGHT trial, patients receiving zolbetuximab plus chemotherapy showed a median PFS of 10.61 months, significantly higher than the 8.67 months in the chemotherapy alone group. The median OS was also improved, with 18.23 months for the zolbetuximab group versus 15.54 months for the chemotherapy group. 87% of patients receiving zolbetuximab experienced grade 3 or higher adverse effects, compared to 78% in the placebo group. The most frequent adverse effects were nausea, vomiting, and reduced appetite.

Finally, the GLOW trial further supported these findings, demonstrating a median PFS of 8.21 months for the zolbetuximab group versus 6.80 months for the chemotherapy group, and a median OS of 14.39 months versus 12.16 months, respectively. Here, grade 3 or higher TEAEs occurred in 72.8% of those in the zolbetuximab arm vs 69.9% of those in the placebo arm. The most common grade 3 or higher TEAEs were vomiting, anemia, decreased neutrophil count, and nausea.

References:

1. Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 22-25 July 2024. Accessed 30 July 2024. https://www.ema.europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use-chmp-22-25-july-2024
2. Junshi Biosciences Announces Positive Opinion from the European Medicines Agency’s CHMP For Toripalimab. News release. Junshi Biosciences. July 26, 2024. Accessed 30 July 2024. https://www.globenewswire.com/news-release/2024/07/26/2919683/0/en/Junshi-Biosciences-Announces-Positive-Opinion-from-the-European-Medicines-Agency-s-CHMP-For-Toripalimab.html
3. H.-Q. Mai et al., “Toripalimab plus chemotherapy for recurrent or metastatic nasopharyngeal carcinoma: the JUPITER-02 randomized clinical trial,” JAMA, vol. 330, no. 20, p. 1961, Nov. 2023, doi: 10.1001/jama.2023.20181.
4. Z.-X. Wang et al., “Toripalimab plus chemotherapy in treatment-naïve, advanced esophageal squamous cell carcinoma (JUPITER-06): A multi-center phase 3 trial,” Cancer Cell, vol. 40, no. 3, pp. 277-288.e3, Mar. 2022, doi: 10.1016/j.ccell.2022.02.007.
5. Astellas Receives Positive CHMP Opinion for Zolbetuximab in Combination with Chemotherapy for Treatment of Advanced Gastric and Gastroesophageal Junction Cancer. News release. Astellas Pharma, Inc. July 26, 2024. Accessed 30 July 2024. https://newsroom.astellas.us/2024-07-26-Astellas-Receives-Positive-CHMP-Opinion-for-Zolbetuximab-in-Combination-with-Chemotherapy-for-Treatment-of-Advanced-Gastric-and-Gastroesophageal-Junction-Cancer.
6. K. Shitara et al., “Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial,” Lancet, vol. 401, no. 10389, pp. 1655–1668, May 2023, doi: 10.1016/s0140-6736(23)00620-7.
7. M. A. Shah et al., “Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial,” Nature Medicine, vol. 29, no. 8, pp. 2133–2141, Jul. 2023, doi: 10.1038/s41591-023-02465-7.