Adakras Adagrasib INN

I. Basic Information

Generic Name: Adagrasib Tablets

English Name: Adagrasib

Brand Names: Krazati, MRTX849, Adakras

Specification: 200 mg/tablet; 42 tablets/box

Drug Class: Irreversible covalent inhibitor of KRAS G12C; targets mutated KRAS protein; indicated for solid tumors with KRAS G12C mutations.

Manufacturer: Everest Pharmaceuticals Ltd.

Description: Film-coated tablets; when the coating is removed, the core is off-white in color.

II. Indications

1. Non-Small Cell Lung Cancer (NSCLC): Indicated for adult patients with locally advanced or metastatic NSCLC harboring a KRAS G12C mutation, whose disease has progressed following at least one prior systemic therapy.

2. Colorectal Cancer (CRC): In combination with cetuximab, indicated for advanced CRC harboring a KRAS G12C mutation, following failure of prior chemotherapy regimens including fluoropyrimidine, oxaliplatin, and irinotecan.

3. May be used for other solid tumors harboring KRAS G12C mutations, such as pancreatic cancer (off-label use).

III. Dosage and Administration

Standard Dosage

600 mg (3 tablets), orally, twice daily. Doses should be taken at fixed times in the morning and evening. May be taken with or without food. Tablets must be swallowed whole; do not chew, crush, or split the tablets. Continue treatment until disease progression or until intolerable toxicity occurs.

Dosage Adjustment (Dose Reduction for Adverse Reactions)

1. First dose reduction: 400 mg (2 tablets), twice daily.

2. Second dose reduction: 600 mg (3 tablets), once daily.

3. Unable to tolerate 600 mg once daily: Permanently discontinue the drug.

Management of Missed Doses/Vomiting

Missed dose (< 4 hours late): Take the missed dose immediately. Missed dose (> 4 hours late): Skip the missed dose and take the next scheduled dose at the regular time; do not take a double dose.

Vomiting after administration: Do not take a replacement dose; simply take the next scheduled dose at the regular time.

IV. Contraindications

1. Contraindicated in patients with a known hypersensitivity to adagrasib or to any of the excipients contained in this product. 2. Contraindicated in patients with severe hepatic or renal insufficiency, or severe prolongation of the QT interval.

3. Contraindicated in pregnant women, women planning to conceive, and breastfeeding women.

V. Pharmacological Action

Irreversibly binds to the mutated KRAS G12C protein, thereby blocking the downstream RAS-MAPK signaling pathway and inhibiting tumor cell proliferation, invasion, and metastasis. Characterized by a long half-life and sustained target inhibition, it demonstrates a low rate of acquired resistance and is effective in patients who have developed resistance to chemotherapy or immunotherapy.

VI. Adverse Reactions

Common (≥10%; mild to moderate severity; generally well-tolerated)

Diarrhea, nausea, vomiting, fatigue, decreased appetite, abdominal pain, constipation, abnormal liver function, QT interval prolongation, edema, musculoskeletal pain, and peripheral numbness.

Uncommon

Pneumonia, interstitial lung disease, pancreatitis, hypokalemia, alopecia, and rash.

Severe/Rare

Severe gastrointestinal bleeding, severe liver injury, severe cardiac arrhythmias, interstitial pneumonitis, and heart failure. If any of these occur, discontinue the medication immediately and seek medical attention.

VII. Important Precautions

1. Gastrointestinal Toxicity: Diarrhea is the most common adverse event; patients should have anti-diarrheal medications on hand in advance. Severe dehydration requires fluid replacement.

2. Cardiac Toxicity: Monitor the QT interval via ECG regularly; avoid concomitant use of medications known to prolong the QT interval.

3. Liver Injury: Monitor liver function prior to treatment and every two weeks thereafter; adjust the dosage promptly if abnormalities are detected.

4. Interstitial Lung Disease (ILD): Immediately investigate for ILD if symptoms such as dry cough, shortness of breath, or dyspnea occur.

5. Drug Interactions: Avoid concomitant use of strong CYP3A inhibitors or inducers; strictly avoid concomitant use of antiarrhythmic medications (e.g., amiodarone) or other agents known to induce arrhythmias.

6. Incurable Disease: This medication does not cure the tumor but serves only to control its progression; regular follow-up CT scans and genetic testing are required.

VIII. Storage

Keep tightly sealed. Store in a cool, dry place below 25°C. Keep out of reach of children.

How to Choose: Sotorasib, Fuzerece Tablets, Gesorece Tablets, or Adagrasib? Sotorasib, Adagrasib, Fuzerece Tablets, and Gesorece Tablets all belong to the class of KRAS G12C-targeted therapies. They are primarily used to treat non-small cell lung cancer (NSCLC) harboring the KRAS G12C mutation; however, they differ in aspects such as their status as "original/domestic products," their developing companies, their market launch status, and their clinical data profiles.

**Key Distinctions Among the Three**

*   **Sotorasib:** Developed by Amgen (USA). It was the world's first KRAS G12C inhibitor to market; it boasts mature clinical data but comes with a high price tag.

*   **Adagrasib:** Developed by Mirati Therapeutics (USA). It is often the preferred choice for patients with brain metastases and carries a relatively high cost.

*   **Fuzerece Tablets:** Developed by Innovent Biologics (China). Positioned as a domestic alternative, it features moderately mature clinical data and is eligible for reimbursement under national medical insurance.

*   **Gesorece Tablets:** Jointly developed by Chia Tai Tianqing (China) and InventisBio (China). Its clinical data is relatively recent/emerging.

**I. If Prioritizing "Efficacy Above All Else"**

**Priority Choice:** Adagrasib

Currently, many oncologists believe that the overall clinical activity of Adagrasib is slightly superior to that of Sotorasib.

This superiority is particularly evident in cases involving: brain metastases, duration of disease control (PFS), and depth of therapeutic response.

In certain studies, Adagrasib has demonstrated: a higher ORR (Objective Response Rate), a longer PFS, and stronger control over CNS (Central Nervous System) metastases.

Consequently—especially for patients with brain metastases—an increasing number of clinicians are now leaning toward Adagrasib.

**II. If Prioritizing "Stability, Safety, and Maturity"**

**Priority Choice:** Sotorasib

This was the world's very first KRAS G12C-targeted therapy to be approved.

**Advantages:** It possesses the most extensive global clinical experience, is the most familiar option to physicians, offers greater safety stability, and is associated with relatively milder side effects.

Some analyses suggest that while Adagrasib may offer slightly stronger efficacy, Sotorasib demonstrates superior tolerability.

**Therefore:** For patients who are elderly, have compromised liver function, or are physically frail, many physicians will—conversely—opt to consider Sotorasib as their first-line choice.

**III. If Operating on a Limited Budget**

**Domestic Therapies Offer a Distinct Advantage:** Gesorece Tablets and Fuzerece Tablets

**Typically:** These options feature lower pricing, are more readily accessible through domestic distribution channels, and are eligible for reimbursement under national medical insurance, thereby helping to alleviate the financial burden for many patients. However, the challenges are also very real: a lack of long-term real-world data, international Phase III trial data, and large-scale data regarding drug resistance.

Currently, its data profile remains less mature than that of sotorasib or adagrasib.

IV. Current Trends in Clinical Practice

The prevailing trends in clinical practice are becoming increasingly evident:

For standard second-line or later-line treatment, sotorasib is the more common choice.

For patients prioritizing superior efficacy, adagrasib is the more common choice.

For patients with brain metastases, adagrasib is the more common choice.

For patients with limited budgets, domestically produced medications are the more common choice.

Product Specifications

Product Name: Adagrasib Tablets (200 mg; 42 tablets/box) — Adakras (Adagrasib INN)

Common Name: Adagrasib Tablets

Active Ingredient: Adagrasib

Dosage Form: Tablets

Specification: 200 mg/tablet; 42 tablets/box

Manufacturer: Everest Pharmaceuticals Ltd.

Indications: 1. Non-Small Cell Lung Cancer (NSCLC): Indicated for adult patients with locally advanced or metastatic NSCLC harboring a *KRAS* G12C mutation, whose disease has progressed following at least one prior line of systemic therapy.

2. Colorectal Cancer (CRC): Indicated (in combination with cetuximab) for patients with advanced CRC harboring a *KRAS* G12C mutation, whose disease has progressed following prior chemotherapy regimens involving fluoropyrimidine, oxaliplatin, and irinotecan.

3. May be used for other solid tumors harboring *KRAS* G12C mutations (e.g., pancreatic cancer) as an off-label clinical application.

Dosage and Administration: Standard Dosage

600 mg (3 tablets) taken orally twice daily. Doses should be taken at fixed times in the morning and evening, either with or without food. Tablets must be swallowed whole; they must not be chewed, crushed, or split. Treatment should be continued until disease progression or the onset of intolerable toxicity.

Dosage Adjustment (Dose Reduction for Adverse Reactions)

1. First Dose Reduction: 400 mg (2 tablets) taken orally twice daily.

2. Second Dose Reduction: 600 mg (3 tablets) taken orally once daily.

3. Inability to tolerate 600 mg once daily: Permanently discontinue the medication.