LUMAKRAS® (sotorasib)

LUMAKRAS safety and tolerability were evaluated in 204 NSCLC patients¹

US Prescribing Information

The most common adverse reactions ≥ 20% were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough in CodeBreaK 100 (N=204)¹

Adverse reactions (≥ 10%) of patients with KRAS G12C–mutated NSCLC who received LUMAKRAS in CodeBreaK 100 (N=204)^1,*

	All Grades (%)	Grades 3 to 4 (%)
Gastrointestinal disorders
Diarrhea	42	5
Nausea	26	1
Vomiting	17	1.5
Constipation	16	0.5
Abdominal pain^†	15	1
Hepatobiliary disorders
Hepatotoxicity^‡	25	12
Respiratory, thoracic, and mediastinal disorders
Cough^§	20	1.5
Dyspnea**	16	2.9
Musculoskeletal and connective tissue disorders
Musculoskeletal pain^††	35	8
Arthralgia	12	1
General disorders and administration site conditions
Fatigue^‡‡	26	2
Edema^§§	15	0
Metabolism and nutrition disorders
Decreased appetite	13	1
Infections and infestations
Pneumonia***	12	7
Skin and subcutaneous tissue disorders
Rash^†††	12	0

*Grading defined by NCI CTCAE version 5.0.

^†Abdominal pain includes abdominal pain, abdominal pain upper, abdominal pain lower.¹

^‡Hepatotoxicity includes alanine aminotransferase increased, aspartate aminotransferase increased, blood bilirubin increased, drug-induced liver injury, hepatitis, hepatotoxicity, liver function test increased, transaminases increased.¹

^§Cough includes cough, productive cough, and upper-airway cough syndrome.¹

**Dyspnea includes dyspnea and dyspnea exertional.¹

^††Musculoskeletal pain includes back pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort, musculoskeletal pain, myalgia, neck pain, non-cardiac chest pain, and pain in extremity.¹

^‡‡Fatigue includes fatigue and asthenia.¹

^§§Edema includes generalized edema, localized edema, edema, edema peripheral, periorbital edema, and testicular edema.¹

***Pneumonia includes pneumonia, pneumonia aspiration, pneumonia bacterial, and pneumonia staphylococcal.¹

^†††Rash includes dermatitis, dermatitis acneiform, rash, rash-maculopapular, rash pustular.¹

Use of anti-emetic and anti-diarrheal medications in CodeBreaK 100:²

26% of patients received an anti-emetic
32% of patients received an anti-diarrheal

had a grade 5 AR1

Grade 5 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%)

discontinued LUMAKRAS due to adverse reactions1

Adverse reactions resulting in permanent discontinuation of LUMAKRAS in ≥ 2% of patients included hepatotoxicity (4.9%)

had a dose reduction1

5% of patients experienced a dose reduction due to an adverse reaction

had a dosage interruption1

34% of patients experienced a dosage interruption due to an adverse reaction

USPI monitoring and dose modification requirements for warnings and precautions¹

	Warnings and precautions	Monitoring and dose modification	Relevant clinical data
	Hepatotoxicity	Monitor liver function tests (ALT, AST, 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 elevation Withhold, dose reduce or permanently discontinue LUMAKRAS based on severity of adverse reaction. Please reference the Dose Modification section for detailed guidance	Among 357 patients who received LUMAKRAS in CodeBreaK 100, hepatotoxicity occurred in 1.7% (all grades) and 1.4% (Grade 3) of patients A total of 18% of patients who received LUMAKRAS had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); 6% were Grade 3 and 0.6% were Grade 4 The median time to first onset of increased ALT/AST was 9 weeks (range: 0.3–42) Increased ALT/AST leading to dose interruption or reduction occurred in 7% of patients. LUMAKRAS was discontinued due to increased ALT/AST in 2% of patients In addition to dose interruption or reduction, 5% of patients received corticosteroids for the treatment of hepatotoxicity
	Interstitial Lung Disease (ILD)/Pneumonitis	Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, fever) Immediately withhold LUMAKRAS in patients with suspected ILD/pneumonitis and permanently discontinue LUMAKRAS if no other potential causes of ILD/pneumonitis are identified	Among 357 patients who received LUMAKRAS in CodeBreaK 100, ILD/pneumonitis occurred in 0.8% of patients, all cases were Grade 3 or 4 at onset, and 1 case was fatal The median time to first onset for ILD/pneumonitis was 2 weeks (range: 2–18 weeks) LUMAKRAS was discontinued due to ILD/pneumonitis in 0.6% of patients

Other considerations¹

	Category	Considerations
	No QTc prolongation	Per the USPI cardiac electrophysiology section in Pharmacodynamics, at the approved recommended dosage, LUMAKRAS does not cause large mean increases in the QTc interval (> 20 msec) The LUMAKRAS USPI does not contain any requirements to monitor ECGs and electrolytes
	No gastrointestinal warnings and precautions	At the approved recommended dosage, LUMAKRAS USPI does not include a warnings and precautions section on severe gastrointestinal adverse reactions The most common adverse reactions (≥ 20%) were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough

Select laboratory abnormalities (≥ 20%) that worsened from baseline in patients with KRAS G12C–mutated NSCLC who received LUMAKRAS in CodeBreaK 100 (N=204^‡‡‡)¹

	Grades 1 to 4 (%)	Grades 3 to 4 (%)
Chemistry
Increased aspartate aminotransferase	39	9
Increased alanine aminotransferase	38	11
Decreased calcium	35	0
Increased alkaline phosphatase	33	2.5
Increased urine protein	29	3.9
Decreased sodium	28	1
Decreased albumin	22	0.5
Hematology
Decreased lymphocytes	48	2
Decreased hemoglobin	43	0.5
Increased activated partial thromboplastin time	23	1.5

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 sodium¹

^‡‡‡N=number of patients who had at least one on-study assessment for the parameter of interest.¹

Are you looking for information on patient characteristics
from the pivotal CodeBreaK 100 Phase 2 trial?

IMPORTANT SAFETY INFORMATION

Hepatotoxicity

LUMAKRAS can cause hepatotoxicity, which may lead to drug-induced liver injury and hepatitis.
Among 357 patients who received LUMAKRAS in CodeBreaK 100, hepatotoxicity occurred in 1.7% (all grades) and 1.4% (Grade 3). A total of 18% of patients who received LUMAKRAS had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); 6% were Grade 3 and 0.6% were Grade 4. In addition to dose interruption or reduction, 5% of patients received corticosteroids for the treatment of hepatotoxicity.
Monitor liver function tests (ALT, AST, 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, dose reduce or permanently discontinue LUMAKRAS based on severity of adverse reaction.

Interstitial Lung Disease (ILD)/Pneumonitis

LUMAKRAS can cause ILD/pneumonitis that can be fatal. Among 357 patients who received LUMAKRAS in CodeBreaK 100 ILD/pneumonitis occurred in 0.8% of patients, all cases were Grade 3 or 4 at onset, and 1 case was fatal. LUMAKRAS was discontinued due to ILD/pneumonitis in 0.6% of patients.
Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold LUMAKRAS in patients with suspected ILD/pneumonitis and permanently discontinue LUMAKRAS if no other potential causes of ILD/pneumonitis are identified.

Most common adverse reactions

The most common adverse reactions ≥ 20% were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough.

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 H₂ receptor antagonists while taking LUMAKRAS.
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.

INDICATION

LUMAKRAS 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, 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). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Please see full Prescribing Information.

Important Safety Information

Hepatotoxicity

LUMAKRAS can cause hepatotoxicity, which may lead to drug-induced liver injury and hepatitis.
Among 357 patients who received LUMAKRAS in CodeBreaK 100, hepatotoxicity occurred in 1.7% (all grades) and 1.4% (Grade 3). A total of 18% of patients who received LUMAKRAS had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); 6% were Grade 3 and 0.6% were Grade 4. In addition to dose interruption or reduction, 5% of patients received corticosteroids for the treatment of hepatotoxicity.
Monitor liver function tests (ALT, AST, 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, dose reduce or permanently discontinue LUMAKRAS based on severity of adverse reaction.

Adverse reactions

LUMAKRAS safety and tolerability were evaluated in 204 NSCLC patients1

US Prescribing Information

The most common adverse reactions ≥ 20% were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough in CodeBreaK 100 (N=204)1

Adverse reactions (≥ 10%) of patients with KRAS G12C–mutated NSCLC who received LUMAKRAS in CodeBreaK 100 (N=204)1,*

Use of anti-emetic and anti-diarrheal medications in CodeBreaK 100:2

USPI monitoring and dose modification requirements for warnings and precautions1

Other considerations1

Select laboratory abnormalities (≥ 20%) that worsened from baseline in patients with KRAS G12C–mutated NSCLC who received LUMAKRAS in CodeBreaK 100 (N=204‡‡‡)1