LUMAKRAS sotorasib 320 mg Tablet, Coated, 90-count
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Other antineoplastic agents class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Sotorasib is used to treat certain types of lung cancer (non-small cell lung cancer; NSCLC) and cancer of the colon (large intestine) or rectum. Sotorasib is in a class of medications called KRAS inhibitors. It works by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps stop or slow the spread of cancer cells.
Read the full MedlinePlus article ↗- KRAS G12C is a specific genetic mutation found in some cancer cells that causes them to grow uncontrollably. It's like a stuck 'on' switch in the cancer cell. Lumakras was designed...
- What exactly is Lumakras treating — what does the KRAS G12C mutation mean?
- This is a really important one to talk about with your care team. Common heartburn and acid reflux medications — including PPIs like omeprazole or Prilosec, and H2 blockers like fa...
- Can I take my heartburn medication while I'm on Lumakras?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Sotorasib — tap one for details:
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💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII M28OL1HH48
Croscarmellose sodium is a plant-based substance derived from cellulose. It acts as a disintegrant, helping tablets and capsules break down quickly in the digestive system so the medicine can be absorbed.
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UNII EWQ57Q8I5X
Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
4 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $239.89 | $21,589.93 / 90 tablets |
| Medicare drug plans payPart D · Q2 2026 | $243.30 | $21,897.17 / 90 tablets |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Lumakras 320 mgthis 55513-0504-50 | Amgen | 90 tablets | — | — | FDA listed | — |
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⏳ Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 11426404 ↗ | Method of use | U-3306 | Sep 15, 2040 |
| US 11236091 ↗ | Drug substance | U-3306 | May 20, 2040 |
| US 11426404 ↗ | Method of use | U-3306 | Sep 15, 2040 |
| US 12398133 ↗ | Drug substance | U-3306 | May 20, 2040 |
| US 12398133 ↗ | Drug substance | U-4107 | May 20, 2040 |
| US 12398133 ↗ | Drug substance | U-4107 | May 20, 2040 |
| US 12398133 ↗ | Drug substance | U-4107 | May 20, 2040 |
| US 12398133 ↗ | Drug substance | U-3306 | May 20, 2040 |
| US 12398133 ↗ | Drug substance | U-3306 | May 20, 2040 |
| US 12280056 ↗ | Method of use | U-4107 | Nov 18, 2039 |
| US 12280056 ↗ | Method of use | U-4107 | Nov 18, 2039 |
| US 12280056 ↗ | Method of use | U-4107 | Nov 18, 2039 |
| US 11426404 ↗ | Method of use | U-4107 | Sep 15, 2040 |
| US 11426404 ↗ | Method of use | U-4107 | Sep 15, 2040 |
| US 11426404 ↗ | Method of use | U-4107 | Sep 15, 2040 |
| US 11236091 ↗ | Drug substance | U-4107 | May 20, 2040 |
| US 11236091 ↗ | Drug substance | U-4107 | May 20, 2040 |
| US 11236091 ↗ | Drug substance | U-4107 | May 20, 2040 |
| US 11827635 ↗ | Drug substance | U-4107 | May 20, 2040 |
| US 11827635 ↗ | Drug substance | U-4107 | May 20, 2040 |
| US 11827635 ↗ | Drug substance | U-4107 | May 20, 2040 |
| US 11827635 ↗ | Drug substance | U-3306 | May 20, 2040 |
| US 11426404 ↗ | Method of use | U-3306 | Sep 15, 2040 |
| US 11236091 ↗ | Drug substance | U-3306 | May 20, 2040 |
| US 11236091 ↗ | Drug substance | U-3306 | May 20, 2040 |
| US 11827635 ↗ | Drug substance | U-3306 | May 20, 2040 |
| US 11827635 ↗ | Drug substance | U-3306 | May 20, 2040 |
| US 10519146 ↗ | Drug substance | — | May 21, 2038 |
| US 10519146 ↗ | Drug substance | — | May 21, 2038 |
| US 10519146 ↗ | Drug substance | — | May 21, 2038 |
| Code | What it grants | Expires |
|---|---|---|
| I-962 | New indication (3-year) | Jan 16, 2028 |
| NCE | New Chemical Entity (5-year) | May 28, 2026 |
| ODE-352 | Orphan Drug Exclusivity (7-year) | May 28, 2028 |
| ODE-507 | Orphan Drug Exclusivity (7-year) | Jan 16, 2032 |
| I-962 | New indication (3-year) | Jan 16, 2028 |
| NCE | New Chemical Entity (5-year) | May 28, 2026 |
| ODE-352 | Orphan Drug Exclusivity (7-year) | May 28, 2028 |
| ODE-507 | Orphan Drug Exclusivity (7-year) | Jan 16, 2032 |
| I-962 | New indication (3-year) | Jan 16, 2028 |
| NCE | New Chemical Entity (5-year) | May 28, 2026 |
| ODE* | Orphan Drug Exclusivity (7-year) | May 28, 2028 |
| ODE-507 | Orphan Drug Exclusivity (7-year) | Jan 16, 2032 |
Is there a generic version of LUMAKRAS 320 MG TABLET?
The FDA approved a generic — why can’t I get it at my pharmacy yet?
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🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 55513-0504-50 You're viewing this | 1 BOTTLE, PLASTIC in 1 CARTON (55513-504-50) / 90 TABLET, COATED in 1 BOTTLE, PLASTIC | 2023-02-02 | Active |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | ✓ Available |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE LUMAKRAS is an inhibitor of the RAS GTPase family indicated for: KRAS G12C-mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) As a single agent, for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC, as determined by an FDA-approved test, who have received at least one prior systemic therapy. ( 1.1 ) This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
( 1.1 ) KRAS G12C-mutated Metastatic Colorectal Cancer (mCRC) In combination with panitumumab, for the treatment of adult patients with KRAS G12C-mutated mCRC as determined by an FDA approved-test, who have received prior fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy. ( 1.2 )
1.1KRAS G12C-mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) LUMAKRAS as a single agent is indicated for the treatment of adult patients with KRAS G12C -mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test [see Dosage and Administration (2.1) ] , who have received at least one prior systemic therapy. This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR) [see Clinical Studies (14.1) ] .
Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
1.2KRAS G12C-mutated Metastatic Colorectal Cancer (mCRC) LUMAKRAS, in combination with panitumumab, is indicated for the treatment of adult patients with KRAS G12C -mutated metastatic colorectal cancer (mCRC), as determined by an FDA-approved test, who have received prior fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy [see Dosage and Administration (2.1) and Clinical Studies (14.2) ] .
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Recommended dosage as a single agent for NSCLC and in combination with panitumumab for mCRC: 960 mg orally once daily. ( 2.2 ) Swallow tablets whole with or without food. ( 2.2 )
2.1Patient Selection KRAS G12C-mutated Locally Advanced or Metastatic NSCLC Select patients for treatment of locally advanced or metastatic NSCLC with LUMAKRAS based on the presence of KRAS G12C mutation in tumor or plasma specimens. If no mutation is detected in a plasma specimen, test tumor tissue [see Clinical Studies (14.1) ]. KRAS G12C-mutated mCRC Select patients for treatment of mCRC based on the presence of KRAS G12C mutation in tumor specimens [see Clinical Studies (14.2) ].
Information on FDA-approved tests for the detection of KRAS G12C mutations is available at: http://www.fda.gov/CompanionDiagnostics.
2.2Recommended Dosage and Administration LUMAKRAS as a Single Agent for KRAS G12C-mutated Locally Advanced or Metastatic NSCLC The recommended dosage of LUMAKRAS is 960 mg (three 320 mg tablets or four 240 mg tablets or eight 120 mg tablets) orally once daily until disease progression or unacceptable toxicity. LUMAKRAS in Combination with Panitumumab for KRAS G12C-mutated mCRC The recommended dosage of LUMAKRAS is 960 mg (three 320 mg tablets or four 240 mg tablets or eight 120 mg tablets) orally once daily in combination with panitumumab until disease progression or unacceptable toxicity.
Administer the first dose of LUMAKRAS prior to first panitumumab infusion. Refer to the panitumumab full prescribing information for recommended panitumumab dosage information. Take the daily dose of LUMAKRAS at the same time each day with or without food [see Clinical Pharmacology (12.3) ] .
Swallow tablets whole. Do not chew, crush or split tablets . If a dose of LUMAKRAS is missed by more than 6 hours, take the next dose as prescribed the next day.
Do not take 2 doses at the same time to make up for the missed dose. If vomiting occurs after taking LUMAKRAS, do not take an additional dose. Take the next dose as prescribed the next day.
Administration to Patients Who Have Difficulty Swallowing Solids Disperse tablets in 120 mL (4 ounces) of non-carbonated, room-temperature water without crushing. No other liquids should be used. Stir or swirl the cup for approximately 3 minutes until tablets are dispersed into small pieces (the tablets will not completely dissolve) and drink immediately or within 2 hours.
The appearance of the mixture may range from pale yellow to bright yellow. Swallow the tablet dispersion. Do not chew pieces of the tablet.
Rinse the container with an additional 120 mL (4 ounces) of water and drink. If the mixture is not consumed immediately, stir the mixture again to ensure that tablets are dispersed.
2.3Dosage Modifications for Adverse Reactions LUMAKRAS dose reduction levels are summarized in Table 1. If adverse reactions occur, a maximum of two dose reductions are permitted. Discontinue LUMAKRAS if patients are unable to tolerate the minimum dose of 240 mg once daily.
When LUMAKRAS is administered in combination with panitumumab, and LUMAKRAS is temporarily withheld or permanently discontinued, temporarily withhold or permanently discontinue panitumumab, respectively [see Clinical Studies (14.2) ] . Refer to the full prescribing information of panitumumab for dose modifications for adverse reactions associated with the use of panitumumab. Treatment with LUMAKRAS as a single agent may be continued if panitumumab is permanently discontinued [see Clinical Pharmacology (12.1) , Clinical Studies (14.2) ].
Refer to Table 2 for dose modification guidelines and management of adverse reactions associated with the use of LUMAKRAS as a single agent or as combination therapy with panitumumab. Table 1. Recommended LUMAKRAS Dose Reduction Levels for Adverse Reactions Dose Reduction Level Dose First dose reduction 480 mg (two 240 mg or four 120 mg tablets) once daily Second dose reduction 240 mg (one 240 mg or two 12…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Tablets: 320 mg, beige, oval-shaped, immediate release, film-coated, debossed with "AMG" on one side and "320" on the opposite side. Tablets: 240 mg, yellow, oval-shaped, immediate release, film-coated, debossed with "AMG" on one side and "240" on the opposite side. Tablets: 120 mg, yellow, oblong-shaped, immediate release, film-coated, debossed with "AMG" on one side and "120" on the opposite side.
Tablets: 320 mg, 240 mg, 120 mg. ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS None. None. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Hepatotoxicity: Monitor liver function tests every 3 weeks for the first 3 months of treatment then once monthly as clinically indicated. Consider administering systemic corticosteroids and withhold, reduce the dose, or permanently discontinue LUMAKRAS based on the severity. ( 2.3 , 5.1 ) Interstitial Lung Disease (ILD)/Pneumonitis: Monitor for new or worsening pulmonary symptoms.
Immediately withhold LUMAKRAS for suspected ILD/pneumonitis and permanently discontinue if no other potential causes of ILD/pneumonitis are identified. ( 2.3 , 5.2 )
5.1Hepatotoxicity LUMAKRAS can cause hepatotoxicity and increased alanine aminotransferase (ALT) or increased aspartate aminotransferase (AST) which may lead to drug-induced liver injury and hepatitis. In the pooled safety population of patients with NSCLC who received single agent LUMAKRAS 960 mg [see Adverse Reactions (6.1) ] , hepatotoxicity occurred in 27% of patients, of which 16% were Grade ≥ 3. Among patients with hepatotoxicity who required dosage modifications, 64% required treatment with corticosteroids.
In this pooled safety population of patients with NSCLC who received single agent LUMAKRAS 960 mg, 17% of patients who received LUMAKRAS had increased ALT/increased AST; of which 9% were Grade ≥ 3. The median time to first onset of increased ALT/AST was 6.3 weeks (range: 0.4 to 42). Increased ALT/AST leading to dose interruption or reduction occurred in 9% of patients treated with LUMAKRAS.
LUMAKRAS was permanently discontinued due to increased ALT/AST in 2.7% of patients. Drug-induced liver injury occurred in 1.6% (all grades) including 1.3% (Grade ≥ 3). In this pooled safety population of patients with NSCLC who received single agent LUMAKRAS 960 mg, a total of 40% patients with recent (≤ 3 months) immunotherapy prior to starting LUMAKRAS had an event of hepatotoxicity.
An event of hepatotoxicity was observed in 18% of patients who started LUMAKRAS more than 3 months after last dose of immunotherapy and in 17% of those who never received immunotherapy. Regardless of time from prior immunotherapy, 94% of hepatotoxicity events improved or resolved with dosage modification of LUMAKRAS, with or without corticosteroid treatment. In the pooled safety population of patients with CRC who received LUMAKRAS 960 mg in combination with panitumumab [see Adverse Reactions (6.1) ] , hepatotoxicity occurred in 15% of patients, of which 4.8% were Grade 3.
A total of 7% of patients who received LUMAKRAS had increased ALT or increased AST, of which 0.8% were Grade 3. The median time to first onset of increased ALT or increased AST was 10 weeks (range: 2 to 22). Increased ALT or increased AST leading to dose interruption occurred in 2.4% of patients.
A total of 3.2% of patients who received LUMAKRAS had hyperbilirubinemia, of which 2.4% were Grade 3. The median time to first onset of hyperbilirubinemia was 12 weeks (range: 0, 29). Hyperbilirubinemia leading to dose interruption occurred in 1.6% of patients.
Among patients with hepatotoxicity, 21% received corticosteroids. Monitor liver function tests (ALT, AST, alkaline phosphatase and total bilirubin) prior to the start of LUMAKRAS, every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations. Withhold, reduce the dose or permanently discontinue LUMAKRAS based on severity of the adverse reaction [see Dosage and Administration (2.3) and Adverse Reactions (6.1) ].
Consider administering systemic corticosteroids for the management of hepatotoxicity.
5.2Interstitial Lung Disease (ILD)/Pneumonitis LUMAKRAS can cause ILD/pneumonitis that can be fatal. In the pooled safety population of patients with NSCLC who received single agent LUMAKRAS 960 mg [see Adverse Reactions (6.1) ] , ILD/pneumonitis occurred in 2.2% of patients, of which 1.1% were Grade ≥ 3, and 1 case was fatal. The median time to fi…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: Hepatotoxicity [see Warnings and Precautions (5.1) ] Interstitial Lung Disease (ILD)/Pneumonitis [see Warnings and Precautions (5.2) ] Single agent in NSCLC: The most common adverse reactions (≥ 20%) were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough. The most common laboratory abnormalities (≥ 25%) were decreased lymphocytes, decreased hemoglobin, increased aspartate aminotransferase, increased alanine aminotransferase, decreased calcium, increased alkaline phosphatase, increased urine protein, and decreased sodium.
( 6.1 ) In combination with panitumumab in CRC: The most common adverse reactions (≥ 20%) in clinical trials of LUMAKRAS in combination with panitumumab are rash, dry skin, diarrhea, stomatitis, fatigue and musculoskeletal pain. The most common Grade 3 or 4 laboratory abnormalities in ≥ 2 patients (4.3%) were decreased magnesium, decreased potassium, decreased corrected calcium, and increased potassium. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Amgen Inc. at 1-800-77-AMGEN (1-800-772-6436) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The pooled safety population described in the WARNINGS AND PRECAUTIONS reflect exposure to LUMAKRAS as a single agent at 960 mg orally once daily until disease progression or unacceptable toxicity in 549 patients with NSCLC with KRAS G12C mutation in the following trials: CodeBreaK 200 (NCT04303780), CodeBreaK 100 (NCT03600883), CodeBreaK 101 (NCT04185883) and CodeBreaK 105 (NCT04380753).
Among these 549 patients who received LUMAKRAS, 44% were exposed for 6 months or longer and 21% were exposed for greater than one year. The pooled safety population described in WARNINGS AND PRECAUTIONS also reflects exposure to LUMAKRAS 960 mg once daily in combination with panitumumab in 126 patients who received LUMAKRAS in combination with panitumumab for mCRC in CodeBreaK 300 (NCT05198934) and CodeBreaK 101 (NCT04185883). Among the 126 patients who received LUMAKRAS 960 mg in combination with panitumumab, 40% were exposed for 6 months or longer and 10% were exposed for greater than one year.
Metastatic Non-Small Cell Lung Cancer The safety of LUMAKRAS was evaluated in a subset of patients with KRAS G12C -mutated locally advanced or metastatic NSCLC in CodeBreaK 100 [see Clinical Studies (14.1) ] . Patients received LUMAKRAS 960 mg orally once daily until disease progression or unacceptable toxicity (n = 204). Among patients who received LUMAKRAS, 39% were exposed for 6 months or longer and 3% were exposed for greater than one year.
The median age of patients who received LUMAKRAS was 66 years (range: 37 to 86); 55% female; 80% White, 15% Asian, and 3% Black. Serious adverse reactions occurred in 50% of patients treated with LUMAKRAS. Serious adverse reactions in ≥ 2% of patients were pneumonia (8%), hepatotoxicity (3.4%), and diarrhea (2%).
Fatal adverse reactions occurred in 3.4% of patients who received LUMAKRAS due to respiratory failure (0.8%), pneumonitis (0.4%), cardiac arrest (0.4%), cardiac failure (0.4%), gastric ulcer (0.4%), and pneumonia (0.4%). Permanent discontinuation of LUMAKRAS due to an adverse reaction occurred in 9% of patients. Adverse reactions resulting in permanent discontinuation of LUMAKRAS in ≥ 2% of patients included hepatotoxicity (4.9%).
Dosage interruptions of LUMAKRAS due to an adverse reaction occurred in 34% of patients. Adverse reactions which required dosage interruption in ≥ 2% of patients were hepatotoxicity (11%), diarrhea (8%), musculoskeletal pain (3.9%), nausea (2.9%), and pneumo…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Acid-Reducing Agents: Avoid coadministration with proton pump inhibitors (PPIs) and H 2 receptor antagonists. If an acid-reducing agent cannot be avoided, administer LUMAKRAS 4 hours before or 10 hours after a local antacid. ( 2.4 , 7.1 ) Strong CYP3A4 Inducers: Avoid coadministration with strong CYP3A4 inducers.
( 7.1 ) CYP3A4 Substrates: Avoid coadministration with CYP3A4 substrates for which minimal concentration changes may lead to therapeutic failures of the substrate. If coadministration cannot be avoided, adjust the substrate dosage in accordance to its Prescribing Information. ( 7.2 ) P-gp substrates: Avoid coadministration with P-gp substrates for which minimal concentration changes may lead to serious toxicities.
If coadministration cannot be avoided, decrease the substrate dosage in accordance to its Prescribing Information. ( 7.2 )
7.1Effects of Other Drugs on LUMAKRAS Acid-Reducing Agents The solubility of sotorasib is pH-dependent. Coadministration of LUMAKRAS with gastric acid-reducing agents decreased sotorasib concentrations [see Clinical Pharmacology (12.3) ] , which may reduce the efficacy of sotorasib. Avoid coadministration of LUMAKRAS with proton pump inhibitors (PPIs), H 2 receptor antagonists, and locally acting antacids.
If coadministration with an acid-reducing agent cannot be avoided, administer LUMAKRAS 4 hours before or 10 hours after administration of a locally acting antacid [see Dosage and Administration (2.4) ] . Strong CYP3A4 Inducers Sotorasib is a CYP3A4 substrate. Coadministration of LUMAKRAS with a strong CYP3A4 inducer decreased sotorasib concentrations [see Clinical Pharmacology (12.3) ] , which may reduce the efficacy of sotorasib.
Avoid coadministration of LUMAKRAS with strong CYP3A4 inducers .
7.2Effects of LUMAKRAS on Other Drugs CYP3A4 Substrates Sotorasib is a CYP3A4 inducer. Coadministration of LUMAKRAS with a CYP3A4 substrate decreased its plasma concentrations [see Clinical Pharmacology (12.3) ] , which may reduce the efficacy of the substrate. Avoid coadministration of LUMAKRAS with CYP3A4 sensitive substrates, for which minimal concentration changes may lead to therapeutic failures of the substrate.
If coadministration cannot be avoided, increase the sensitive CYP3A4 substrate dosage in accordance with its Prescribing Information . P-glycoprotein (P-gp) Substrates Sotorasib is a P-gp inhibitor. Coadministration of LUMAKRAS with a P-gp substrate increased its plasma concentrations [see Clinical Pharmacology (12.3) ] , which may increase the adverse reactions of the substrate.
Avoid coadministration of LUMAKRAS with P-gp substrates, for which minimal concentration changes may lead to serious toxicities. If coadministration cannot be avoided, decrease the P-gp substrate dosage in accordance with its Prescribing Information . Breast Cancer Resistance Protein (BCRP) Substrates Sotorasib is a BCRP-inhibitor.
Coadministration of LUMAKRAS with a BCRP substrate increased its plasma concentrations [see Clinical Pharmacology (12.3) ] , which may increase the risk of adverse reactions of the substrate. When coadministered with LUMAKRAS, monitor for adverse reactions of the BCRP substrate and decrease the BCRP substrate dosage in accordance with its Prescribing Information.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 )
8.1Pregnancy Risk Summary There are no available data on LUMAKRAS use in pregnant women. In rat and rabbit embryo-fetal development studies, oral sotorasib did not cause adverse developmental effects or embryo-lethality at exposures up to 4.6 times the human exposure at the 960 mg clinical dose (see Data ) . Refer to the Full Prescribing Information of panitumumab for pregnancy risk information and contraception recommendations when LUMAKRAS is administered in combination with panitumumab.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In a rat embryo-fetal development study, once daily oral administration of sotorasib to pregnant rats during the period of organogenesis resulted in maternal toxicity at the 540 mg/kg dose level (approximately 4.6 times the human exposure based on area under the curve (AUC) at the clinical dose of 960 mg). Sotorasib did not cause adverse developmental effects and did not affect embryo-fetal survival at doses up to 540 mg/kg.
In a rabbit embryo-fetal development study, once daily oral administration of sotorasib during the period of organogenesis resulted in lower fetal body weights and a reduction in the number of ossified metacarpals in fetuses at the 100 mg/kg dose level (approximately 2.6 times the human exposure based on AUC at the clinical dose of 960 mg), which was associated with maternal toxicity including decreased body weight gain and food consumption during the dosing phase. Sotorasib did not cause adverse developmental effects and did not affect embryo-fetal survival at doses up to 100 mg/kg.
8.2Lactation Risk Summary There are no data on the presence of sotorasib or its metabolites in human milk, the effects on the breastfed child, or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with LUMAKRAS and for 1 week after the last dose. Refer to the Full Prescribing Information of panitumumab for lactation recommendations when LUMAKRAS is administered in combination with panitumumab.
8.4Pediatric Use The safety and effectiveness of LUMAKRAS have not been established in pediatric patients.
8.5Geriatric Use Of the 357 patients with any tumor type who received LUMAKRAS 960 mg orally once daily in CodeBreaK 100, 46% were 65 and over, and 10% were 75 and over. No overall differences in safety or effectiveness were observed between older patients and younger patients treated with LUMAKRAS as a single agent. In a pooled analysis of 132 patients who received LUMAKRAS 960 mg in combination with panitumumab for KRAS G12C-mutated mCRC, 30% were 65 and over while 9% were 75 and over.
No overall differences in safety or efficacy were observed between older patients (≥ 65 years of age) compared to younger patients, treated with LUMAKRAS 960 mg in combination with panitumumab.
8.6Hepatic Impairment No dosage modification is recommended in patients with mild to moderate hepatic impairment (Child-Pugh A or B). The effect of severe hepatic impairment (Child-Pugh C) on the safety of LUMAKRAS is unknown . Monitor for sotorasib adverse reactions in patients with hepatic impairment more frequently since these patients may be at increased risk for adverse reactions including hepatotoxicity [see Clinical Pharmacology (12.3) ].
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary There are no available data on LUMAKRAS use in pregnant women. In rat and rabbit embryo-fetal development studies, oral sotorasib did not cause adverse developmental effects or embryo-lethality at exposures up to 4.6 times the human exposure at the 960 mg clinical dose (see Data ) . Refer to the Full Prescribing Information of panitumumab for pregnancy risk information and contraception recommendations when LUMAKRAS is administered in combination with panitumumab.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In a rat embryo-fetal development study, once daily oral administration of sotorasib to pregnant rats during the period of organogenesis resulted in maternal toxicity at the 540 mg/kg dose level (approximately 4.6 times the human exposure based on area under the curve (AUC) at the clinical dose of 960 mg). Sotorasib did not cause adverse developmental effects and did not affect embryo-fetal survival at doses up to 540 mg/kg.
In a rabbit embryo-fetal development study, once daily oral administration of sotorasib during the period of organogenesis resulted in lower fetal body weights and a reduction in the number of ossified metacarpals in fetuses at the 100 mg/kg dose level (approximately 2.6 times the human exposure based on AUC at the clinical dose of 960 mg), which was associated with maternal toxicity including decreased body weight gain and food consumption during the dosing phase. Sotorasib did not cause adverse developmental effects and did not affect embryo-fetal survival at doses up to 100 mg/kg.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of LUMAKRAS have not been established in pediatric patients.
🧓 Geriatric Use ▾
8.5Geriatric Use Of the 357 patients with any tumor type who received LUMAKRAS 960 mg orally once daily in CodeBreaK 100, 46% were 65 and over, and 10% were 75 and over. No overall differences in safety or effectiveness were observed between older patients and younger patients treated with LUMAKRAS as a single agent. In a pooled analysis of 132 patients who received LUMAKRAS 960 mg in combination with panitumumab for KRAS G12C-mutated mCRC, 30% were 65 and over while 9% were 75 and over.
No overall differences in safety or efficacy were observed between older patients (≥ 65 years of age) compared to younger patients, treated with LUMAKRAS 960 mg in combination with panitumumab.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Sotorasib is an inhibitor of KRAS G12C, a tumor-restricted, mutant-oncogenic form of the RAS GTPase, KRAS. Sotorasib forms an irreversible, covalent bond with the unique cysteine of KRAS G12C, locking the protein in an inactive state that prevents downstream signaling without affecting wild-type KRAS. Sotorasib blocked KRAS signaling, inhibited cell growth, and promoted apoptosis only in KRAS G12C tumor cell lines.
Sotorasib inhibited KRAS G12C in vitro and in vivo with minimal detectable off-target activity. In mouse tumor xenograft models, sotorasib-treatment led to tumor regressions and prolonged survival, and was associated with anti-tumor immunity in KRAS G12C models. In the setting of KRAS G12C-mutant CRC, epidermal growth factor receptor (EGFR) activation has been identified as a mechanism of resistance to KRAS G12C inhibition.
In a murine patient-derived colorectal tumor xenograft model, the combination of sotorasib and panitumumab, an EGFR antagonist, had increased antitumor activity compared to either sotorasib or panitumumab alone.
12.2Pharmacodynamics Sotorasib exposure-response relationships and the time course of the pharmacodynamic response are unknown. Cardiac Electrophysiology At the approved recommended dosage, LUMAKRAS does not cause large mean increases in the QTc interval (> 20 msec).
12.3Pharmacokinetics The pharmacokinetics of sotorasib have been characterized in healthy subjects and in patients with KRAS G12C -mutated solid tumors, including NSCLC. Sotorasib exhibited non-linear, time-dependent, pharmacokinetics over the dose range of 180 mg to 960 mg (0.19 to 1 time the approved recommended dosage) once daily with similar systemic exposure (i.e., AUC 0-24h and C max ) across doses at steady state. Sotorasib systemic exposure was comparable between film-coated tablets and film-coated tablets predispersed in water administered under fasted conditions.
Sotorasib plasma concentrations reached steady state within 22 days. No accumulation was observed after repeat LUMAKRAS dosages with a mean accumulation ratio of 0.56 (coefficient of variation (CV): 59%). Absorption The median time to sotorasib peak plasma concentration is 1 hour.
Effect of Food When 960 mg LUMAKRAS was administered with a high-fat, high-calorie meal (containing approximately 800 to 1000 calories with 150, 250, and 500 to 600 calories from protein, carbohydrate and fat, respectively) in patients, sotorasib AUC 0-24h increased by 25% compared to administration under fasted conditions. Distribution The sotorasib mean volume of distribution (V d ) at steady state is 211 L (CV: 135%). In vitro , sotorasib plasma protein binding is 89%.
Elimination The sotorasib mean terminal elimination half-life is 5 hours (standard deviation (SD): 2). At 960 mg LUMAKRAS once daily, the sotorasib steady state apparent clearance is
26.2L/hr (CV: 76%). Metabolism The main metabolic pathways of sotorasib are non-enzymatic conjugation and oxidative metabolism with CYP3As. Excretion After a single dose of radiolabeled sotorasib, 74% of the dose was recovered in feces (53% unchanged) and 6% (1% unchanged) in urine.
Specific Populations No clinically meaningful differences in the pharmacokinetics of sotorasib were observed based on age (28 to 86 years), sex, race (White, Black and Asian), body weight (36.8 to 157.9 kg), line of therapy, ECOG PS (0, 1), mild and moderate renal impairment (eGFR: ≥ 30 mL/min/1.73 m 2 ), or mild hepatic impairment (AST or ALT < 2.5 × ULN or total bilirubin < 1.5 × ULN). The effect of severe renal impairment on sotorasib pharmacokinetics has not been studied. Hepatic Impairment The mean AUC of sotorasib decreased by 25% in subjects with moderate hepatic impairment (Child-Pugh B) and increased by 4% in subjects with severe hepatic impairment (Child-Pugh C) compared to subjects with normal hepatic function following a single dose of 960 mg LUMAKRAS.
Clinical Studies Acid-Reducing Agents :…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Sotorasib is an inhibitor of KRAS G12C, a tumor-restricted, mutant-oncogenic form of the RAS GTPase, KRAS. Sotorasib forms an irreversible, covalent bond with the unique cysteine of KRAS G12C, locking the protein in an inactive state that prevents downstream signaling without affecting wild-type KRAS. Sotorasib blocked KRAS signaling, inhibited cell growth, and promoted apoptosis only in KRAS G12C tumor cell lines.
Sotorasib inhibited KRAS G12C in vitro and in vivo with minimal detectable off-target activity. In mouse tumor xenograft models, sotorasib-treatment led to tumor regressions and prolonged survival, and was associated with anti-tumor immunity in KRAS G12C models. In the setting of KRAS G12C-mutant CRC, epidermal growth factor receptor (EGFR) activation has been identified as a mechanism of resistance to KRAS G12C inhibition.
In a murine patient-derived colorectal tumor xenograft model, the combination of sotorasib and panitumumab, an EGFR antagonist, had increased antitumor activity compared to either sotorasib or panitumumab alone.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied LUMAKRAS (sotorasib) 320 mg tablets are beige, oval-shaped, film-coated, debossed with "AMG" on one side and "320" on the opposite side, and are supplied as follows: Carton containing one bottle of 90 tablets with child-resistant closure, NDC 55513-504-50 LUMAKRAS (sotorasib) 240 mg tablets are yellow, oval-shaped, film-coated, debossed with "AMG" on one side and "240" on the opposite side, and are supplied as follows: Carton containing one bottle of 120 tablets with child-resistant closure, NDC 55513-512-60 LUMAKRAS (sotorasib) 120 mg tablets are yellow, oblong-shaped, film-coated, debossed with "AMG" on one side and "120" on the opposite side, and are supplied as follows: Carton containing two bottles of 120 tablets with child-resistant closure, NDC 55513-488-02 Carton containing one bottle of 240 tablets with child-resistant closure, NDC 55513-488-24 Storage and Handling Store at 20°C to 25°C (68°F to 77°F).
Excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature] .
📦 Storage and Handling ▾
Storage and Handling Store at 20°C to 25°C (68°F to 77°F). Excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature] .
📋 Description ▾
11 DESCRIPTION Sotorasib is an inhibitor of the RAS GTPase family. The molecular formula is C 30 H 30 F 2 N 6 O 3 , and the molecular weight is 560.6 g/mol. The chemical name of sotorasib is 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-(1M)-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-4-[(2S)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl]pyrido[2,3-d]pyrimidin-2(1H)-one.
The chemical structure of sotorasib is shown below: Sotorasib has pKa values of 8.06 and 4.56. The solubility of sotorasib in the aqueous media decreases over the range pH 1.2 to 6.8 from 1.3 mg/mL to 0.03 mg/mL. LUMAKRAS is supplied as film-coated tablets for oral use containing 320 mg, 240 mg or 120 mg of sotorasib.
Inactive ingredients in the tablet core are microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, and magnesium stearate. The film coating material consists of polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, iron oxide yellow and iron oxide red (320 mg tablet only). Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Hepatotoxicity Advise patients to immediately contact their healthcare provider for signs and symptoms of liver dysfunction [see Warnings and Precautions (5.1) ] . Interstitial Lung Disease (ILD)/Pneumonitis Advise patients to contact their healthcare provider immediately to report new or worsening respiratory symptoms [see Warnings and Precautions (5.2) ] .
Lactation Advise women not to breastfeed during treatment with LUMAKRAS and for 1 week after the last dose [see Use in Specific Populations (8.2) ] . Refer to the Full Prescribing Information of panitumumab for lactation information, when LUMAKRAS is used in combination with panitumumab. Drug Interactions Advise patients to inform their healthcare provider of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, dietary and herbal products.
Inform patients to avoid proton pump inhibitors, and H 2 receptor antagonists while taking LUMAKRAS [see Drug Interactions (7.1) and (7.2) ] . If coadministration with an acid-reducing agent cannot be avoided, inform patients to take LUMAKRAS 4 hours before or 10 hours after a locally acting antacid [see Dosage and Administration (2.4) ] . Missed Dose If a dose of LUMAKRAS is missed by greater than 6 hours, resume treatment as prescribed the next day [see Dosage and Administration (2.2) ] .