I. Basic Information

Generic Name: Zongertinib Tablets

English Name: Zongertinib

Brand Names: Shenghetu, HERNEXEOS, LuciZonger

Dosage Form: Oval, biconvex, film-coated tablets.

Specification: 60 mg/tablet; 60 tablets/box.

R&D Company: Boehringer Ingelheim; co-developed by Merck (MSD) outside the U.S.

Manufacturer: Lucius Pharmaceutical (Laos) Co., Ltd.

Drug Approval Number: 12 L 1427/26

II. Indications

Patient Population: Adults with unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) who meet the following criteria:

The tumor harbors an activating mutation in the HER2 (ERBB2) tyrosine kinase domain (confirmed by an FDA-approved test).

Have previously received systemic therapy (e.g., platinum-based chemotherapy, HER2-targeted ADCs, etc.).

Basis for Approval: Based on Objective Response Rate (ORR) and Duration of Response (DOR); continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.

III. Dosage and Administration

Recommended Dosage:

Body weight < 90 kg: 120 mg once daily (QD);

Body weight ≥ 90 kg: 180 mg once daily (QD).

Administration: Administer orally on an empty stomach or with food. Swallow tablets whole; do not break, crush, or chew.

Missed Dose: If a dose is missed, take it as soon as possible within 12 hours; if more than 12 hours have passed, skip the missed dose and resume the regular dosing schedule.

Vomiting: If vomiting occurs, do not take an additional dose; resume the regular dosing schedule.

Dose Adjustment: Dose reduction or discontinuation may be required based on adverse reactions such as hepatic dysfunction, cardiac toxicity, or Interstitial Lung Disease (ILD).

IV. Contraindications

No specific contraindications identified; however, caution is advised regarding the risk of severe adverse reactions.

V. Warnings and Precautions

Hepatotoxicity:

Incidence: Hepatic dysfunction (elevated ALT/AST) occurred in 27% of patients, with Grade 3–4 events occurring in ≤ 2% of patients. Monitoring: Assess ALT/AST/bilirubin every 2 weeks prior to treatment and during the first 12 weeks; thereafter, monitor once monthly. Increase monitoring frequency in the event of elevated transaminase levels.

Management: For Grade 3 or 4 hepatic dysfunction, suspend treatment until recovery to Grade ≤1 or baseline; subsequently, resume treatment at a reduced dose. Permanently discontinue the drug in cases of Grade 4 total bilirubin, or when AST/ALT levels are ≥3 times the Upper Limit of Normal (ULN) accompanied by bilirubin levels ≥2 times the ULN.

Cardiac Toxicity (Left Ventricular Dysfunction):

Incidence: Grade 3 decline in Left Ventricular Ejection Fraction (LVEF) occurred in 1.9% of patients.

Monitoring: Assess LVEF prior to initiating treatment and monitor periodically throughout the treatment course.

Interstitial Lung Disease (ILD):

Incidence: ILD occurred in 1.4% of patients, with 0.7% classified as Grade 3.

Management: For Grade 2 or higher ILD, suspend treatment until recovery to Grade ≤1. Permanently discontinue the drug in cases of Grade 3 or 4 ILD.

Drug Interactions:

CYP3A Inducers: Resume the original dose 7–14 days after discontinuing the inducer.

BCRP Substrates (e.g., Rosuvastatin): May result in increased exposure; monitor closely for adverse reactions.

P-gp Substrates (e.g., Digoxin): May increase toxicity; dose adjustment may be required.

VI. Adverse Reactions

Common Adverse Reactions: Diarrhea, nausea, vomiting, decreased appetite, rash, pruritus, stomatitis, fatigue, edema, pyrexia, cough, dyspnea, headache, dizziness, myalgia, arthralgia.

Serious Adverse Reactions: Hepatotoxicity, cardiac toxicity, ILD.

VII. Use in Specific Populations

Pregnancy: Contraindicated; may cause fetal malformations.

Lactation: Breastfeeding is prohibited during treatment and for 2 weeks following the final dose.

Hepatic and Renal Impairment: No dose adjustment is required for mild impairment; data are insufficient for moderate to severe impairment.

Geriatric Patients: Patients aged ≥65 years constituted 46% of the study population; no differences in safety were observed compared to younger patients.

Pediatric Patients: Safety and efficacy have not been established. VIII. Drug Interactions

**Avoid Concomitant Use:** Strong CYP3A inducers (e.g., rifampin).

**Monitor Concomitant Use:** BCRP/P-gp substrates (e.g., rosuvastatin, digoxin).

IX. Patient Education Points

**Administration Instructions:** Strictly adhere to weight-based dosing; do not self-adjust the dosage. Swallow tablets whole; do not split.

**Adverse Event Management:** Seek medical attention promptly in the event of diarrhea. Discontinue the medication immediately in cases of severe hepatotoxicity.

**Contraception and Pregnancy:** Female patients must use effective contraception throughout the treatment period. Use is contraindicated during pregnancy.

X. Clinical Trial Data (Beamion LUNG-1 Study)

**Study Population:** 71 patients with HER2-mutated NSCLC (median line of therapy: 1; 78% had received prior immunotherapy).

**Efficacy Data:**

ORR (Overall Response Rate): 75% (6% Complete Response, 69% Partial Response);

58% of patients achieved a DOR (Duration of Response) of ≥ 6 months;

ORR in patients with brain metastases: 60% (3 out of 5 evaluable patients).

XI. Storage Conditions

**Storage:** Store in the original container at 20°C–25°C; excursions between 15°C–30°C are permitted. Use within 3 months after opening. The bottle contains a desiccant packet; do not ingest.

XII. Other Information

**Packaging:** 60 tablets per box.

**Shelf Life:** Refer to the expiration date marked on the outer packaging.

**Company Profile**

Lucius Pharmaceutical (Laos) Co., Ltd. (hereinafter referred to as "Lucius Pharmaceutical") is a modern, multinational, high-tech biopharmaceutical enterprise. Currently, the company operates one global R&D center and collaborates with three leading R&D teams within the industry. Specializing in the research and development of complex chemical formulations and biologics, the company has achieved significant technological breakthroughs in key generic drugs. Today, Lucius Pharmaceutical stands as one of the global leaders in the R&D of patented generic drugs, enjoying an excellent professional reputation and strong market standing within the industry. In 2020, Lucius Pharmaceutical officially launched its Asia-Pacific strategy, investing substantial capital to construct the "Asia-Pacific No. 1 Smart Factory" in Vientiane, the capital of Laos. Adhering to GMP production standards, the facility incorporates cutting-edge pharmaceutical equipment sourced from China, the United States, Germany, and other global leaders. It features an international-standard, high-end formulation workshop with an annual production capacity for generic drugs exceeding 1.5 billion tablets. The company's product portfolio currently encompasses over 200 categories—including oncology, cardiovascular, hematology, diabetes, dermatology, men's health, and anti-aging—and is exported to more than 50 countries and regions across Europe, South America, Africa, the Middle East, India, Vietnam, and Nepal.

In Laos, Lucius has established a pharmaceutical manufacturing facility that currently sets the highest production standards within the country. Since the completion and commissioning of the Lucius Laos plant, the company has committed to collaborating with the Association of Southeast Asian Nations (ASEAN) to accelerate its internationalization process. By strengthening global intellectual cooperation in pharmaceutical R&D, enriching its product range, and enhancing quality standards, Lucius strives to position itself as a leading global pharmaceutical enterprise.

**Product Specifications**

**Product Name:** Zongertinib Tablets 60mg × 60 Tablets/Box (LuciZonger)

**Common Name:** Zongertinib Tablets

**Active Ingredient:** Zongertinib

**Dosage Form:** Tablets

**Specification:** 60 mg/tablet; 60 tablets/box.

**Manufacturer:** Lucius Pharmaceutical (Laos) Co., Ltd.

**Indications:** For use in adult patients with unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) who meet the following criteria:

* The tumor harbors activating HER2 (ERBB2) tyrosine kinase domain mutations (as detected by an FDA-approved test).

* Patients have received prior systemic therapy (e.g., platinum-based chemotherapy, HER2-targeted ADCs, etc.).

**Basis for Approval:** Approved based on Objective Response Rate (ORR) and Duration of Response (DOR); continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.

**Dosage and Administration:**

**Recommended Dosage:**

* Body weight < 90 kg: 120 mg once daily (QD).

* Body weight ≥ 90 kg: 180 mg once daily (QD).

**Administration Method:** Administer orally, either on an empty stomach or with food. Swallow the tablets whole; do not break, crush, or chew.

**Missed Dose:** If a dose is missed, take the missed dose as soon as possible within 12 hours of the scheduled time. If more than 12 hours have elapsed, skip the missed dose and resume the regular dosing schedule.

**Vomiting:** If vomiting occurs, do not take an additional dose; continue with the regular dosing schedule.

**Dosage Adjustment:** Dosage reduction or discontinuation may be required based on adverse reactions such as hepatic dysfunction, cardiac toxicity, or Interstitial Lung Disease (ILD).