LUMAKRAS
Generic: SOTORASIB
Basic Information
Manufacturer
Amgen Inc
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
c80a362c-7ac3-4894-a076-0691e68ef8c1
Indications & 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 ) 1.1 KRAS 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).
1.2 KRAS 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) ] .
( 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 ) 1.1 KRAS 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).
1.2 KRAS 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) ] .
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.
6.1 Clinical 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 pneumonia (2.5%).
Dose reductions of LUMAKRAS due to an adverse reaction occurred in 5% of patients.
Adverse reactions which required dose reductions in ≥ 2% of patients included increased ALT (2.9%) and increased AST (2.5%).
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.
Table 3 summarizes the common adverse reactions observed in CodeBreaK 100.
Table 3.
Adverse Reactions (≥ 10%) of Patients with KRAS G12C-Mutated NSCLC who Received LUMAKRAS in CodeBreaK 100 Grading defined by NCI CTCAE version 5.0.
Adverse Reaction LUMAKRAS N = 204 All Grades (%) Grades 3 to 4 (%) Gastrointestinal disorders Diarrhea 42 5 Nausea 26 1 Vomiting 17 1.5 Constipation 16 0.5 Abdominal pain Abdominal pain includes abdominal pain, abdominal pain upper, and abdominal pain lower.
15 1.0 Hepatobiliary disorders Hepatotoxicity Hepatotoxicity includes alanine aminotransferase increased, aspartate aminotransferase increased, blood bilirubin increased, drug-induced liver injury, hepatitis, hepatotoxicity, liver function test increased, and transaminases increased.
25 12 Respiratory, thoracic, and mediastinal disorders Cough Cough includes cough, productive cough, and upper-airway cough syndrome.
20 1.5 Dyspnea Dyspnea includes dyspnea and dyspnea exertional.
16 2.9 Musculoskeletal and connective tissue disorders Musculoskeletal pain 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.
35 8 Arthralgia 12 1.0 General disorders and administration site conditions Fatigue Fatigue includes fatigue and asthenia.
26 2.0 Edema Edema includes generalized edema, localized edema, edema, edema peripheral, periorbital edema, and testicular edema.
15 0 Metabolism and nutrition disorders Decreased appetite 13 1.0 Infections and infestations Pneumonia Pneumonia includes pneumonia, pneumonia aspiration, pneumonia bacterial, and pneumonia staphylococcal.
12 7 Skin and subcutaneous tissue disorders Rash Rash includes dermatitis, dermatitis acneiform, rash, rash-maculopapular, and rash pustular.
12 0 Table 4 summarizes the selected laboratory adverse reactions observed in CodeBreaK 100.
Table 4.
Select Laboratory Abnormalities (≥ 20%) that Worsened from Baseline in Patients with KRAS G12C-Mutated NSCLC who Received LUMAKRAS in CodeBreaK 100 Laboratory Abnormalities LUMAKRAS N = 204 N = number of patients who had at least one on-study assessment for the parameter of interest.
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 1.0 Decreased albumin 22 0.5 Hematology Decreased lymphocytes 48 2 Decreased hemoglobin 43 0.5 Increased activated partial thromboplastin time 23 1.5 Metastatic Colorectal Cancer The safety of LUMAKRAS in combination with panitumumab was evaluated in the CodeBreaK 300 study [see Clinical Studies (14.2) ] .
Patients with KRAS G12C-mutated mCRC received LUMAKRAS 960 mg orally once daily in combination with panitumumab 6 mg/kg intravenously (IV) once every 2 weeks (N = 47), LUMAKRAS 240 mg orally once daily in combination with panitumumab 6 mg/kg IV once every 2 weeks (N = 50), or the investigator's choice of standard of care (SOC) trifluridine/ tipiracil or regorafenib (N = 50).
Among patients who received LUMAKRAS 960 mg orally once daily in combination with panitumumab, 36% were exposed to LUMAKRAS for greater than 6 months and 6% were exposed for greater than 12 months.
The median age of patients who received LUMAKRAS 960 mg in combination with panitumumab arm was 63 years (range: 37-79 years); 38% were age 65 years or older; 49% were female; 79% were White and 13% were Asian.
Serious adverse reactions occurred in 26% of patients receiving LUMAKRAS 960 mg in combination with panitumumab.
Serious adverse reactions in ≥ 2 patients receiving LUMAKRAS 960 mg in combination with panitumumab were sepsis (6%) and intestinal obstruction (4.3%).
Fatal adverse reactions occurred in 2 patients (4.3%) receiving LUMAKRAS 960 mg in combination with panitumumab, consisting of cardiac arrest and sepsis (1 patient each).
Permanent discontinuation of LUMAKRAS due to an adverse reaction occurred in 1 patient for decreased corrected calcium.
Dosage interruptions of LUMAKRAS due to an adverse reaction occurred in 26% of patients.
Adverse reactions which required dosage interruption in ≥ 2 patients were rash, hepatotoxicity and intestinal obstruction.
A dose reduction of LUMAKRAS due to an adverse reaction occurred in 1 patient for nausea.
The most common adverse reactions (≥ 20%) in patients receiving LUMAKRAS 960 mg in combination with panitumumab were rash, dry skin, diarrhea, stomatitis, fatigue and musculoskeletal pain.
The most common Grade 3-4 laboratory abnormalities in ≥ 2 patients (4.3%) were decreased magnesium, decreased potassium, decreased corrected calcium, and increased potassium.
Table 5 and Table 6 summarize the adverse reactions and laboratory abnormalities, respectively, identified in CodeBreaK 300.
Table 5.
Adverse Reactions (≥ 10%) in Patients with KRAS G12C-Mutated mCRC who Received LUMAKRAS 960 mg in Combination with Panitumumab in CodeBreaK 300 Adverse Reaction LUMAKRAS 960 mg in combination with panitumumab N = 47 Trifluridine/tipiracil or regorafenib N = 50 All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Skin and subcutaneous tissue disorders Rash Rash includes dermatitis acneiform, dermatosis, drug eruption, eczema, erythema, hand dermatitis, rash, rash erythematous, rash maculo-papular, rash papular, rash pruritic, rash pustular, and skin toxicity.
87 26 8 2 Dry skin Dry skin includes dry skin, xerosis, and xeroderma.
28 0 2 0 Pruritis 17 0 4 0 Nail Disorder Nail disorders includes nail avulsion, nail cuticle fissure, nail disorder, nail toxicity, and paronychia.
17 0 0 0 Skin fissure 13 0 0 0 Palmar-plantar erythrodysesthesia syndrome 13 0 10 4 Gastrointestinal disorders Diarrhea Diarrhea includes diarrhea, gastroenteritis, and diarrhea hemorrhagic.
28 6 26 0 Stomatitis Stomatitis includes mucosal inflammation, stomatitis, mouth ulceration, angular cheilitis, and cheilitis.
26 0 14 0 Nausea 17 2.1 36 4 Constipation 15 2.1 10 0 Abdominal pain Abdominal pain includes abdominal pain, abdominal pain upper, abdominal pain lower, abdominal discomfort, and hepatic pain.
15 0 18 2 Vomiting 13 2.1 10 2 General disorders Fatigue Fatigue includes asthenia and fatigue.
21 0 34 2 Musculoskeletal and connective tissue disorders Musculoskeletal pain Musculoskeletal pain includes arthralgia, back pain, myalgia, musculoskeletal chest pain, bone pain, and pain in extremity.
21 2.1 14 2 Hematological disorders Hemorrhage Hemorrhage includes epistaxis, gastrointestinal hemorrhage, vaginal hemorrhage, rectal hemorrhage, hematochezia, hemorrhage, hemorrhage urinary tract, hematospermia, and hematuria.
13 2.1 2 0 Eye disorders Conjunctivitis Conjunctivitis includes conjunctival hyperemia, conjunctivitis, and conjunctivitis allergic.
11 0 2 0 Table 6.
Select Laboratory Abnormalities (≥ 20%) that Worsened from Baseline in Patients with KRAS G12C-Mutated mCRC who Received LUMAKRAS 960 mg in combination with panitumumab in CodeBreaK 300 The denominator used to calculate the rate varied from 44 to 46 in the LUMAKRAS + panitumumab arm and 18 to 50 in the trifluridine/tipiracil or regorafenib arm based on the number of patients with a baseline value and at least one post-treatment value.
Laboratory Abnormalities LUMAKRAS 960 mg in combination with panitumumab Trifluridine/tipiracil or Regorafenib All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Chemistry Magnesium decreased 76 24 8 0 Calcium (corrected) decreased 74 4.3 46 0 Aspartate aminotransferase increased 39 0 22 2 Alkaline Phosphatase increased 33 2.2 33 0 Creatine kinase increased 30 2.3 7 0 Alanine Aminotransferase increased 28 0 16 2 Potassium decreased 26 7 12 0 Albumin decreased 26 2.2 22 0 Urine protein increased 23 0 22 6 Potassium increased 22 4.3 6 0 Glucose decreased 22 0 2 0 Hematology Hemoglobin decreased 30 0 58 6 Lymphocytes decreased 26 2.2 56 8 White blood cells decreased 24 0 48 14
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.
6.1 Clinical 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 pneumonia (2.5%).
Dose reductions of LUMAKRAS due to an adverse reaction occurred in 5% of patients.
Adverse reactions which required dose reductions in ≥ 2% of patients included increased ALT (2.9%) and increased AST (2.5%).
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.
Table 3 summarizes the common adverse reactions observed in CodeBreaK 100.
Table 3.
Adverse Reactions (≥ 10%) of Patients with KRAS G12C-Mutated NSCLC who Received LUMAKRAS in CodeBreaK 100 Grading defined by NCI CTCAE version 5.0.
Adverse Reaction LUMAKRAS N = 204 All Grades (%) Grades 3 to 4 (%) Gastrointestinal disorders Diarrhea 42 5 Nausea 26 1 Vomiting 17 1.5 Constipation 16 0.5 Abdominal pain Abdominal pain includes abdominal pain, abdominal pain upper, and abdominal pain lower.
15 1.0 Hepatobiliary disorders Hepatotoxicity Hepatotoxicity includes alanine aminotransferase increased, aspartate aminotransferase increased, blood bilirubin increased, drug-induced liver injury, hepatitis, hepatotoxicity, liver function test increased, and transaminases increased.
25 12 Respiratory, thoracic, and mediastinal disorders Cough Cough includes cough, productive cough, and upper-airway cough syndrome.
20 1.5 Dyspnea Dyspnea includes dyspnea and dyspnea exertional.
16 2.9 Musculoskeletal and connective tissue disorders Musculoskeletal pain 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.
35 8 Arthralgia 12 1.0 General disorders and administration site conditions Fatigue Fatigue includes fatigue and asthenia.
26 2.0 Edema Edema includes generalized edema, localized edema, edema, edema peripheral, periorbital edema, and testicular edema.
15 0 Metabolism and nutrition disorders Decreased appetite 13 1.0 Infections and infestations Pneumonia Pneumonia includes pneumonia, pneumonia aspiration, pneumonia bacterial, and pneumonia staphylococcal.
12 7 Skin and subcutaneous tissue disorders Rash Rash includes dermatitis, dermatitis acneiform, rash, rash-maculopapular, and rash pustular.
12 0 Table 4 summarizes the selected laboratory adverse reactions observed in CodeBreaK 100.
Table 4.
Select Laboratory Abnormalities (≥ 20%) that Worsened from Baseline in Patients with KRAS G12C-Mutated NSCLC who Received LUMAKRAS in CodeBreaK 100 Laboratory Abnormalities LUMAKRAS N = 204 N = number of patients who had at least one on-study assessment for the parameter of interest.
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 1.0 Decreased albumin 22 0.5 Hematology Decreased lymphocytes 48 2 Decreased hemoglobin 43 0.5 Increased activated partial thromboplastin time 23 1.5 Metastatic Colorectal Cancer The safety of LUMAKRAS in combination with panitumumab was evaluated in the CodeBreaK 300 study [see Clinical Studies (14.2) ] .
Patients with KRAS G12C-mutated mCRC received LUMAKRAS 960 mg orally once daily in combination with panitumumab 6 mg/kg intravenously (IV) once every 2 weeks (N = 47), LUMAKRAS 240 mg orally once daily in combination with panitumumab 6 mg/kg IV once every 2 weeks (N = 50), or the investigator's choice of standard of care (SOC) trifluridine/ tipiracil or regorafenib (N = 50).
Among patients who received LUMAKRAS 960 mg orally once daily in combination with panitumumab, 36% were exposed to LUMAKRAS for greater than 6 months and 6% were exposed for greater than 12 months.
The median age of patients who received LUMAKRAS 960 mg in combination with panitumumab arm was 63 years (range: 37-79 years); 38% were age 65 years or older; 49% were female; 79% were White and 13% were Asian.
Serious adverse reactions occurred in 26% of patients receiving LUMAKRAS 960 mg in combination with panitumumab.
Serious adverse reactions in ≥ 2 patients receiving LUMAKRAS 960 mg in combination with panitumumab were sepsis (6%) and intestinal obstruction (4.3%).
Fatal adverse reactions occurred in 2 patients (4.3%) receiving LUMAKRAS 960 mg in combination with panitumumab, consisting of cardiac arrest and sepsis (1 patient each).
Permanent discontinuation of LUMAKRAS due to an adverse reaction occurred in 1 patient for decreased corrected calcium.
Dosage interruptions of LUMAKRAS due to an adverse reaction occurred in 26% of patients.
Adverse reactions which required dosage interruption in ≥ 2 patients were rash, hepatotoxicity and intestinal obstruction.
A dose reduction of LUMAKRAS due to an adverse reaction occurred in 1 patient for nausea.
The most common adverse reactions (≥ 20%) in patients receiving LUMAKRAS 960 mg in combination with panitumumab were rash, dry skin, diarrhea, stomatitis, fatigue and musculoskeletal pain.
The most common Grade 3-4 laboratory abnormalities in ≥ 2 patients (4.3%) were decreased magnesium, decreased potassium, decreased corrected calcium, and increased potassium.
Table 5 and Table 6 summarize the adverse reactions and laboratory abnormalities, respectively, identified in CodeBreaK 300.
Table 5.
Adverse Reactions (≥ 10%) in Patients with KRAS G12C-Mutated mCRC who Received LUMAKRAS 960 mg in Combination with Panitumumab in CodeBreaK 300 Adverse Reaction LUMAKRAS 960 mg in combination with panitumumab N = 47 Trifluridine/tipiracil or regorafenib N = 50 All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Skin and subcutaneous tissue disorders Rash Rash includes dermatitis acneiform, dermatosis, drug eruption, eczema, erythema, hand dermatitis, rash, rash erythematous, rash maculo-papular, rash papular, rash pruritic, rash pustular, and skin toxicity.
87 26 8 2 Dry skin Dry skin includes dry skin, xerosis, and xeroderma.
28 0 2 0 Pruritis 17 0 4 0 Nail Disorder Nail disorders includes nail avulsion, nail cuticle fissure, nail disorder, nail toxicity, and paronychia.
17 0 0 0 Skin fissure 13 0 0 0 Palmar-plantar erythrodysesthesia syndrome 13 0 10 4 Gastrointestinal disorders Diarrhea Diarrhea includes diarrhea, gastroenteritis, and diarrhea hemorrhagic.
28 6 26 0 Stomatitis Stomatitis includes mucosal inflammation, stomatitis, mouth ulceration, angular cheilitis, and cheilitis.
26 0 14 0 Nausea 17 2.1 36 4 Constipation 15 2.1 10 0 Abdominal pain Abdominal pain includes abdominal pain, abdominal pain upper, abdominal pain lower, abdominal discomfort, and hepatic pain.
15 0 18 2 Vomiting 13 2.1 10 2 General disorders Fatigue Fatigue includes asthenia and fatigue.
21 0 34 2 Musculoskeletal and connective tissue disorders Musculoskeletal pain Musculoskeletal pain includes arthralgia, back pain, myalgia, musculoskeletal chest pain, bone pain, and pain in extremity.
21 2.1 14 2 Hematological disorders Hemorrhage Hemorrhage includes epistaxis, gastrointestinal hemorrhage, vaginal hemorrhage, rectal hemorrhage, hematochezia, hemorrhage, hemorrhage urinary tract, hematospermia, and hematuria.
13 2.1 2 0 Eye disorders Conjunctivitis Conjunctivitis includes conjunctival hyperemia, conjunctivitis, and conjunctivitis allergic.
11 0 2 0 Table 6.
Select Laboratory Abnormalities (≥ 20%) that Worsened from Baseline in Patients with KRAS G12C-Mutated mCRC who Received LUMAKRAS 960 mg in combination with panitumumab in CodeBreaK 300 The denominator used to calculate the rate varied from 44 to 46 in the LUMAKRAS + panitumumab arm and 18 to 50 in the trifluridine/tipiracil or regorafenib arm based on the number of patients with a baseline value and at least one post-treatment value.
Laboratory Abnormalities LUMAKRAS 960 mg in combination with panitumumab Trifluridine/tipiracil or Regorafenib All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Chemistry Magnesium decreased 76 24 8 0 Calcium (corrected) decreased 74 4.3 46 0 Aspartate aminotransferase increased 39 0 22 2 Alkaline Phosphatase increased 33 2.2 33 0 Creatine kinase increased 30 2.3 7 0 Alanine Aminotransferase increased 28 0 16 2 Potassium decreased 26 7 12 0 Albumin decreased 26 2.2 22 0 Urine protein increased 23 0 22 6 Potassium increased 22 4.3 6 0 Glucose decreased 22 0 2 0 Hematology Hemoglobin decreased 30 0 58 6 Lymphocytes decreased 26 2.2 56 8 White blood cells decreased 24 0 48 14