Sotonor Sotorasib

[Product Name] Sotorasib Capsules

[English Name] Sotorasib

[Development Code] AMG510

[Genetic Target] KRAS G12C

[Specification] 120 mg × 120 capsules/box

[Manufacturer] INDAR Pharmaceutical Co., Ltd

[Overview]

Sotorasib (AMG 510) is one of the first small-molecule inhibitors to successfully target KRAS and enter human clinical development; it specifically targets and inhibits KRAS proteins harboring the G12C mutation. Sotorasib specifically and irreversibly inhibits the proliferative activity of KRAS G12C mutant proteins by locking them into an inactive, GDP-bound state.

[Indications]

Indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring a KRAS G12C mutation, who have received at least one prior systemic therapy.

[Dosage and Administration]

Recommended Dosage: 960 mg orally once daily.

Take once daily, at approximately the same time each day.

May be taken with or without food.

Swallow tablets whole; do not chew, crush, or split the tablets.

[Adverse Reactions]

The most common adverse reactions (≥ 20%) are diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough. The most common laboratory abnormalities (≥ 25%) are lymphopenia, decreased hemoglobin, increased aspartate aminotransferase (AST), increased alanine aminotransferase (ALT), hypocalcemia, increased alkaline phosphatase, increased urine protein, and hyponatremia.

[Contraindications] None

[Precautions]

Hepatotoxicity: Monitor liver function tests every 3 weeks during the first 3 months of treatment, and monthly thereafter as clinically indicated. Based on severity, withhold, reduce the dose of, or permanently discontinue LuciSot.

Interstitial Lung Disease (ILD)/Pneumonitis: Monitor for new or worsening pulmonary symptoms. For suspected ILD/pneumonitis, immediately withhold LuciSot; if no other potential causes of ILD/pneumonitis are identified, permanently discontinue the drug. [Safety and Efficacy]

Sotorasib was the first KRAS G12C inhibitor to enter clinical development; it now holds the potential to become the first targeted therapy approved for the treatment of patients with advanced non-small cell lung cancer (NSCLC) harboring the KRAS G12C mutation.

The marketing application for Sotorasib is based on positive results from the advanced NSCLC patient cohort in the Phase II CodeBreaK 100 study—a cohort comprising patients whose disease had progressed following prior treatment with chemotherapy and/or immunotherapy. The full results of this study were presented at the virtual 21st World Conference on Lung Cancer (WCLC) in 2020. The data demonstrated that, in patients with advanced NSCLC harboring the KRAS G12C mutation whose disease had progressed after prior chemotherapy and/or PD-1/PD-L1 immunotherapy, Sotorasib exhibited durable anti-tumor activity and a favorable benefit-risk profile: a confirmed objective response rate (ORR) of 37.1%, a disease control rate (DCR) of 80.6%, a median duration of response (DOR) of 10 months, and a median progression-free survival (PFS) of 6.8 months.

[Storage]

Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).

How to Choose: Sotorasib, Fuzerece Tablets, Gesorece Tablets, or Adagrasib?

Sotorasib, Adagrasib, Fuzerece Tablets, and Gesorece Tablets are all targeted therapies for KRAS G12C mutations, primarily indicated for the treatment of non-small cell lung cancer (NSCLC) harboring the KRAS G12C mutation. However, they differ in various aspects, including whether they are original/innovator drugs or domestically produced generics, their respective development companies, their market approval status, and their clinical data. **Key Differences Among the Three**

**Sotorasib:** Developed by Amgen (USA); the world's first KRAS G12C inhibitor; backed by mature clinical data; carries a high price tag.

**Adagrasib:** Developed by Mirati Therapeutics (USA); often the preferred choice for patients with brain metastases; carries a relatively high price tag.

**Fuzeresib Tablets:** Developed by Innovent Biologics (China); positioned as a domestic alternative; supported by moderately mature clinical data; eligible for medical insurance reimbursement.

**Gesoresib Tablets:** Jointly developed by Chia Tai Tianqing and InventisBio (China); supported by relatively early-stage clinical data.

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

**Priority Choice:** Adagrasib

Currently, many oncologists believe that Adagrasib demonstrates slightly stronger overall activity compared to Sotorasib.

It performs particularly well in cases involving brain metastases, progression-free survival (PFS), and achieving deep clinical responses.

In certain studies, it has demonstrated a higher Objective Response Rate (ORR), longer PFS, and superior control over central nervous system (CNS) metastases.

Consequently—especially for patients with brain metastases—there is a growing trend among clinicians to favor Adagrasib.

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

**Priority Choice:** Sotorasib

This was the world's first targeted therapy specifically designed for KRAS G12C mutations.

**Advantages:** It boasts the most extensive global clinical experience, is the most familiar to physicians, offers a more stable safety profile, 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 first.

**III. If Budget Is Limited**

**Domestic Drugs Offer a Distinct Advantage:** Gesoresib Tablets and Fuzeresib Tablets

**Typically:** These options feature lower costs, offer more convenient access via domestic distribution channels, and are eligible for medical insurance reimbursement—thereby significantly alleviating financial burdens for many patients.

**However, a realistic challenge remains:** Data regarding real-world long-term outcomes, international Phase III trials, and large-scale drug resistance patterns...

...are currently not as mature or extensive as those available for Sotorasib and Adagrasib. IV. Current Real-World Trends in Clinical Practice

The current trends in clinical practice have become increasingly evident:

For standard second-line therapy, Sotorasib is the more common choice.

For patients seeking stronger therapeutic 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: Sotorasib 120mg * 120 Capsules/Box (Sotonor)

Common Name: Sotorasib Capsules

Active Ingredient: Sotorasib

Dosage Form: Capsules

Specification: 120mg * 120 Capsules/Box

Manufacturer: INDAR Pharmaceutical Co., Ltd.

Indications: Used for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring a *KRAS* G12C mutation, who have received at least one prior systemic therapy.

Dosage and Administration: Recommended dosage: 960 mg orally once daily.

Take once daily, at approximately the same time each day.

May be taken with or without food.

Swallow the tablets whole; do not chew, crush, or break the tablets.