TOKYO, November 25, 2021 -- Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) announced that it obtained approval from the Ministry of Health, Labour and Welfare (MHLW) for the anti-HER2 humanized monoclonal antibody Herceptin^® Injection 60 and 150 [generic name: trastuzumab] for the additional indication of advanced or recurrent HER2-positive salivary gland cancer not amenable to curative resection. Orphan drug designation had been granted by the MHLW on March 11, 2021 for this indication.

Salivary gland cancer, a type of head and neck cancer, is a rare cancer with less than 1,000 patients newly diagnosed annually in Japan¹. The standard therapy is primarily surgery, and there is no established chemotherapy for this cancer. Unlike other head and neck cancers, salivary gland cancer includes many histological types, associated with diversity in genomic alterations and prognosis. Less than 15% of all salivary cancers in Japan are estimated to be HER2-positive, relatively more common in salivary duct carcinomas.

"We are very pleased that Herceptin has become a new treatment option as the first personalized medicine for salivary gland cancer, for which no standard chemotherapy has been established so far. I’d like to thank everyone who strongly supported us toward the approval based on evidence from Japan, particularly those involved in the investigator-initiated clinical trial that formed the basis for approval," said Chugai’s President and CEO, Dr. Osamu Okuda. "Herceptin has been used as a standard treatment for breast and gastric cancer for many years. We are committed to promoting appropriate use of Herceptin so that it can contribute to the treatment of salivary gland cancer, a cancer with high unmet needs."

The approval is based on a Japanese investigator-initiated phase II clinical study (HUON-003-01 study) with 16 patients with HER2-positive advanced or recurrent salivary gland cancer. The study investigated the efficacy and safety of Herceptin in combination with docetaxel. The primary endpoint was the response rate. 60% of 15 patients in the efficacy analysis population showed response (95%Cl: 32.3 - 83.7). Major adverse events included neutropenia, leukopenia, alopecia, anemia, stomatitis, and hypoalbuminemia.

HER2 protein overexpression and gene amplification should be determined with the pathological testing kit VENTANA ultraView Pathway HER2 (4B5) and VENTANA DISH HER2, both provided by Roche Diagnostics K.K. obtained regulatory approval for the two tests on November 11, 2021 as companion diagnostics for Herceptin to identify advanced or recurrent HER2-positive salivary gland cancer not amenable to curative resection.

[Approval Information] *Changes are underlined.

Indications

• Breast cancer overexpressing HER2
• Advanced or recurrent gastric cancer overexpressing HER2 not amenable to curative resection
• Advanced or recurrent HER2-positive salivary gland cancer not amenable to curative resection

Dosage and administration

• Use either Regimen A or Regimen B for breast cancer overexpressing HER2.
• Use Regimen B for advanced or recurrent gastric cancer overexpressing HER2 not amenable to curative resection, in combination with other antineoplastic agents.
• Use Regimen B in combination with docetaxel formulation for advanced or recurrent HER2-positive salivary gland cancer not amenable to curative resection.

Regimen A: The usual adult dosage is a loading dose of 4 mg/kg (body weight) trastuzumab (genetical recombination) and subsequent doses of 2 mg/kg once a week, each administered by intravenous infusion over at least 90 minutes.

Regimen B: The usual adult dosage is a loading dose of 8 mg/kg (body weight) trastuzumab (genetical recombination) and subsequent doses of 6 mg/kg every 3 weeks, each administered by intravenous infusion over at least 90 minutes.

If the first infusion is well tolerated, subsequent infusions may be administered over a shorter time of at least 30 minutes.

About Herceptin
Herceptin is a humanized monoclonal antibody that targets human epidermal growth factor receptor type 2 (HER2), which is involved in the growth of tumor cells. Herceptin was launched in 2001 for metastatic breast cancer overexpressing HER2. In 2011, it was approved for the treatment of patients with advanced or recurrent gastric cancer overexpressing HER2 not amenable to curative resection.

About Salivary Gland Cancer
Salivary gland cancer is a type of head and neck cancer^2,3 and develops in the cells that form salivary gland tissues. It is characterized by a variety of histological patterns as classified into 21 types⁴, making pathological diagnosis difficult⁵. Recently, gene expression and abnormalities that define features of each histological type have become increasingly clear⁶. About 80% of salivary gland tumors are in the parotid gland, of which about 20% are malignant². Standard therapy includes surgery, radiation therapy, and pharmacological treatment, and no standard chemotherapy has been established for advanced or recurrent salivary gland cancer⁷.

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<Source>

1. Japan Society for Head and Neck Cancer Registry Committee, Report of Head and Neck Cancer Registry of Japan Clinical Statistics of Registered Patients, 2018??http://www.jshnc.umin.ne.jp/pdf/HNCreport_2018.pdf Accessed November 2021
2. Institute of Medical Information Science, ed. Diseases in View vol.13 Otorhinolaryngology, 1st edition, Medic Media, 2020.
3. Japan Society for Head and Neck Cancer, ed. Manual of Head and Neck Cancer, 6th revised edition, Kanehara Shuppan, 2019
4. WHO Classification of Head and Neck Tumors. Fourth edition, 2017
5. Toshitaka Nagao. Ear and nose. 59(Supplement 1): S32-37, 2013
6. Japan Salivary Gland Society, ed. Thorough Lecture on Saliva and Salivary Glands, Kanehara Shuppan, 2016
7. Japan Society for Head and Neck Cancer, ed. Guidelines for the Treatment of Head and Neck Cancer 2018 Edition, Kanehara Shuppan, 2017