Drug Trials Snapshots - LAZCLUZE
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.
Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the LAZCLUZE Prescribing Information for all the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).
Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).
LAZCLUZE (lazertinib)
laz-kluez
Janssen Biotech, Inc.
Original Approval date: August 19, 2024
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
LAZCLUZE is a kinase inhibitor indicated in combination with amivantamab for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test.
How is this drug used?
LAZCLUZE is administered as tablets that are taken by mouth once daily with or without food, given in combination with amivantamab.
Who participated in the clinical trials?
The FDA approved LAZCLUZE in combination with amivantamab based on evidence from one clinical trial (MARIPOSA, NCT04487080) using data from 858 adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations. The trial was conducted at 204 sites in 26 countries including China, South Korea, Brazil, Japan, Malaysia, Spain, Taiwan, Russian Federation, Turkey, Thailand, Mexico, France, Italy, Ukraine, Argentina, Poland, the United States, India, Australia, Portugal, Israel, the United Kingdom, Germany, Belgium, Hungary, and Netherlands. Of the 858 patients, 12 were enrolled at sites in the United States.
Among the 858 patients, all were evaluated for efficacy and 849 were evaluated for safety.
How were the trials designed?
LAZCLUZE in combination with amivantamab was evaluated in one clinical trial using data from 858 patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations.
The MARIPOSA trial is a randomized, active-controlled, multicenter trial. Patients were randomized (2:2:1) to receive LAZCLUZE in combination with amivantamab (N=429), osimertinib (N=429), or LAZCLUZE alone (an unapproved regimen for NSCLC).
LAZCLUZE is administered at 240 mg orally once daily, alone or in combination with amivantamab administered intravenously at 1050 mg (for patients <80 kg) or 1400 mg (for patients ≥80 kg) once weekly for four weeks, then every two weeks thereafter starting at Week 5. Osimertinib is administered at a dose of 80 mg orally once daily.
The evaluation of efficacy for untreated metastatic NSCLC relied upon comparison between LAZCLUZE in combination with amivantamab versus osimertinib. The major efficacy outcome measure was progression-free survival (PFS) as assessed by blinded independent central review (BICR). Additional efficacy outcome measures included overall survival (OS), overall response rate (ORR), and duration of response (DOR).
How were the trials designed?
MARIPOSA is an ongoing, randomized, multicenter trial to compare the efficacy and safety of LAZCLUZE in combination with amivantamab versus osimertinib as first-line treatment in adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations. The contribution of amivantamab to the activity of the combination of LAZCLUZE and amivantamab is also being assessed by comparing the efficacy observed in the LAZCLUZE plus amivantamab arm with that in the LAZCLUZE arm.
Eligible participants were ≥18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place), had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and had histologically or cytologically confirmed, locally advanced or metastatic NSCLC that was treatment-naïve and not amenable to curative therapy including surgical resection or chemoradiation. Other key eligibility criteria included: (1) EGFR exon 19 deletion or exon 21 L858R substitution, as detected by an FDA-approved or other validated test; (2) at least one measurable lesion, according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1; and (3) adequate organ and bone marrow function. Participants who had received any prior systemic treatment at any time for EGFR-mutated NSCLC, had symptomatic brain metastases, or had received any prior treatment with an EGFR tyrosine kinase inhibitor (TKI), were excluded from participation in the study. The protocol did allow for enrollment of patients who received adjuvant or neoadjuvant systemic therapies for EGFR-mutated NSCLC more than 12 months prior to the development of locally advanced or metastatic disease.
Prior EGFR testing in accordance with local standard of care, obtained at or after the diagnosis of locally advanced or metastatic NSCLC and before signing informed consent was used to document EGFR mutation status to minimize delay in treatment initiation. Archival or fresh tissue was submitted for central confirmation of mutation status. If insufficient, a new biopsy was required.
Patients were randomized (2:2:1) to receive LAZCLUZE in combination with amivantamab (N=429), osimertinib (N=429), or LAZCLUZE alone (an unapproved regimen for NSCLC).
LAZCLUZE is administered at 240 mg orally once daily, alone or in combination with amivantamab administered intravenously at 1050 mg (for patients <80 kg) or 1400 mg (for patients ≥80 kg) once weekly for four weeks, then every two weeks thereafter starting at Week 5. Osimertinib is administered at a dose of 80 mg orally once daily.
Treatment started on Cycle 1 Day 1 and continued as 28-day cycles. Post-randomization disease assessments (computed tomography [CT] or magnetic resonance imaging [MRI] tumor imaging) occurred every 8 weeks (±1 week) for the first 30 months, and then every 12 weeks (±1 week). Participants with a history of brain metastasis at screening underwent postbaseline brain MRI every 8 weeks (±1 week) for the first 30 months and then every 12 weeks (±1 week); participants with no history of brain metastasis at screening underwent postbaseline surveillance brain MRI every 24 weeks (±1 week). Study treatment continued until documented disease progression using RECIST v1.1 confirmed by BICR or until discontinuation of study treatment for another reason. Participants who discontinued study treatment for any reason were to be followed for survival and symptomatic progression in the Follow-up phase. Survival, subsequent anti-cancer treatment, and disease status were assessed at least every 12 weeks (±14 days) after the last dose of study treatment or disease progression (whichever occurred first), until the end of study, death, lost to follow-up, or withdrawal of consent, whichever came first.
The evaluation of efficacy in untreated metastatic NSCLC relied upon comparison between LAZCLUZE in combination with amivantamab versus osimertinib. The major efficacy outcome measure was PFS as assessed by BICR. Additional efficacy outcome measures included OS, ORR, and DOR.
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many male and female patients were enrolled in the clinical trial used to evaluate the efficacy of LAZCLUZE.
Figure 1. Baseline Demographics by Sex, Efficacy Population
Source: Adapted from FDA Review
Figure 2 summarizes how many patients by race were enrolled in the clinical trial used to evaluate the efficacy of LAZCLUZE.
Figure 2. Baseline Demographics by Race, Efficacy Population
Source: Adapted from FDA Review
Figure 3 summarizes how many patients by age were enrolled in the clinical trial used to evaluate the efficacy of LAZCLUZE.
Figure 3. Baseline Demographics by Age, Efficacy Population
Source: Adapted from FDA Review
Figure 4 summarizes how many patients by ethnicity were enrolled in the clinical trial used to evaluate the efficacy of LAZCLUZE.
Figure 4. Baseline Demographics by Ethnicity, Efficacy Population
Source: Adapted from FDA Review
Who participated in the trials?
Table 1. Baseline Demographics, Efficacy Population
| Demographic Subgroup | LAZCLUZE + Amivantamab N=429 | Osimertinib N=429 |
|---|---|---|
| Sex, n (%) | ||
| Female | 275 (64) | 251 (59) |
| Male | 154 (36) | 178 (41) |
| Age, years | ||
| Median (range) | 64.0 (25; 88) | 63.0 (28; 88) |
| Age group, years, n (%) | ||
| 18 to 25 | 1 (0.2) | 0 |
| 26 to 50 | 52 (12) | 71 (17) |
| 51 to 64 | 182 (42) | 166 (39) |
| 65 to 74 | 143 (33) | 139 (32) |
| ≥75 | 51 (12) | 53 (12) |
| Race, n (%) | ||
| American Indian or Alaska Native | 7 (1.6) | 7 (1.6) |
| Asian | 250 (58) | 251 (59) |
| Black or African American | 4 (0.9) | 3 (0.7) |
| Native Hawaiian or other Pacific Islander | 1 (0.2) | 1 (0.2) |
| White | 164 (38) | 165 (38) |
| Multiple | 1 (0.2) | 1 (0.2) |
| Unknown | 2 (0.5) | 1 (0.2) |
| Ethnicity, n (%) | ||
| Hispanic or Latino | 56 (13) | 45 (10) |
| Not Hispanic or Latino | 371 (86) | 382 (89) |
| Unknown | 0 | 1 (0.2) |
| Not reported | 2 (0.5) | 1 (0.2) |
Source: Adapted from FDA Review
What are the benefits of this drug?
In the MARIPOSA trial, the median PFS was 23.7 months for patients treated with LAZCLUZE in combination with amivantamab and 16.6 months for patients treated with osimertinib. Preliminary results also showed no trend for LAZCLUZE in combination with amivantamab to decrease OS compared to osimertinib.
What are the benefits of this drug (results of trials used to assess efficacy)?
Efficacy results from the MARIPOSA trial are summarized in Table 2. The major efficacy outcome was PFS.
Table 2. Efficacy Results by BICR Assessment, Efficacy Population
| Parameter | LAZCLUZE + Amivantamab N=429 | Osimertinib N=429 |
|---|---|---|
| Progression-free survival | ||
| Number of events (%) | 192 (45) | 252 (59) |
| Median, months (95% CI) | 23.7 (19.1, 27.7) | 16.6 (14.8, 18.5) |
| HR1,2 (95% CI); p-value1,3 | 0.70 (0.58, 0.85); p=0.0002 | |
| Overall response rate4 | ||
| ORR, % (95% CI) | 78 (74, 82) | 73 (69, 78) |
| Complete response, % | 5 | 3.5 |
| Partial response, % | 73 | 70 |
| Duration of response5 | ||
| Median (95% CI), months | 25.8 (20.1, NE) | 16.7 (14.8, 18.5) |
| Patients with DOR ≥6 months6, % | 86 | 85 |
| Patients with DOR ≥12 months6, % | 68 | 57 |
Source: LAZCLUZE Prescribing Information
1 Stratified by mutation type (exon 19del or exon 21 L858R), prior brain metastases (yes or no), and Asian race (yes or no).
2 Stratified Cox proportional hazards regression.
3 Stratified log-rank test.
4 Confirmed responses based on the ITT population.
5 In confirmed responders.
6 Based on observed rates.
Abbreviations: BICR, blinded independent central review; CI, confidence interval; DOR, duration of response; HR, hazard ration; ITT, intennt-to-treat; NE, not estimable; ORR, overall response rate
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- Sex: LAZCLUZE in combination with amivantamab worked similarly in males and females.
- Race: LAZCLUZE in combination with amivantamab worked similarly in Asians and White patients. The number of patients of other races were small; therefore, differences in how the drug worked in these races could not be determined.
- Age: No overall differences were observed in how LAZCLUZE in combination with amivantamab worked between patients younger and older than 65 years of age.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 3. Progression-Free Survival by Subgroup, Efficacy Population
| Subgroup | LAZCLUZE + Amivantamab N=429 n/Ns (%) | Osimertinib N=429 n/Ns (%) | Hazard Ratio (95% CI) |
|---|---|---|---|
| Sex | |||
| Female | 112/275 (41) | 140/251 (56) | 0.70 (0.55, 0.90) |
| Male | 80/154 (52) | 112/178 (63) | 0.74 (0.55, 0.98) |
| Age group, years | |||
| <65 | 94/235 (40) | 153/237 (65) | 0.50 (0.39, 0.65) |
| ≥65 | 98/194 (51) | 99/192 (52) | 1.06 (0.80, 1.41) |
| Race | |||
| Asian | 105/250 (42) | 144/251 (57) | 0.67 (0.52, 0.86) |
| White | 79/164 (48) | 102/165 (62) | 0.76 (0.58, 1.01) |
| Ethnicity | |||
| Hispanic or Latino | 30/56 (54) | 26/45 (58) | 0.87 (0.51, 1.47) |
| Not Hispanic or Latino | 162/371 (44) | 225/382 (59) | 0.69 (0.56, 0.84) |
Source: Adapted from FDA Review
Abbreviations: CI, confidence interval; N, number of patients in treatment arm; n, number of patients meeting criteria; Ns, total number of patients for each specific subgroup and were assigned to that specific arm
What are the possible side effects?
LAZCLUZE may cause serious side effects, including: lung problems, skin problems, and eye problems. When taken in combination with amivantamab the serious side effect of blood clots may occur.
The most common side effects of LAZCLUZE in combination with amivantamab include: rash; feeling very tired; infected skin around the nail; diarrhea; infusion-related reaction (from amivantamab); constipation; muscle and joint pain; COVID-19; sores in the mouth; bleeding; swelling of hands, ankles, feet, face, or all of the body; decreased appetite; itchy skin; unusual feeling in the skin (such as tingling or crawling); nausea; and changes in certain blood tests. LAZCLUZE may cause fertility problems in males and females, which may affect the ability to have children and may cause risk to a fetus.
What are the possible side effects (results of trials used to assess safety)?
Table 4. Adverse Reactions (≥10%) in Patients With NSCLC With Exon 19 Deletion or Exon 21 L858R Substitution Mutations, Safety Population
| Adverse Reaction | LAZCLUZE + Amivantamab, | Osimertinib, | ||
|---|---|---|---|---|
| Skin and subcutaneous tissue disorders | All Grades % | Grade 3 or 4 % | All Grades % | Grade 3 or 4 % |
| Rash | 86 | 26 | 48 | 1.2 |
| Nail toxicity | 71 | 11 | 34 | 0.7 |
| Dry skin | 25 | 1 | 18 | 0.2 |
| Pruritus | 24 | 0.5 | 17 | 0.2 |
| Injury, poisoning and procedural complications | ||||
| Infusion-related reaction | 63 | 6 | 0 | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Musculoskeletal pain | 47 | 2.1 | 39 | 1.9 |
| Gastrointestinal disorders | ||||
| Stomatitis | 43 | 2.4 | 27 | 0.5 |
| Diarrhea | 31 | 2.6 | 45 | 0.9 |
| Constipation | 29 | 0 | 13 | 0 |
| Nausea | 21 | 1.2 | 14 | 0.2 |
| Vomiting | 12 | 0.5 | 5 | 0 |
| Abdominal pain | 11 | 0 | 10 | 0 |
| Hemorrhoids | 10 | 0.2 | 2.1 | 0.2 |
| General disorders and administration site conditions | ||||
| Edema | 43 | 2.6 | 8 | 0 |
| Fatigue | 32 | 3.8 | 20 | 1.9 |
| Pyrexia | 12 | 0 | 9 | 0 |
| Vascular disorders | ||||
| Venous thromboembolism | 36 | 11 | 8 | 2.8 |
| Hemorrhage | 25 | 1 | 13 | 1.2 |
| Nervous system disorders | ||||
| Paresthesia | 35 | 1.7 | 10 | 0.2 |
| Dizziness | 14 | 0 | 10 | 0 |
| Headache | 13 | 0.2 | 13 | 0 |
| Infections and infestations | ||||
| COVID-19 | 26 | 1.7 | 24 | 1.4 |
| Conjunctivitis | 11 | 0.2 | 1.6 | 0 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 24 | 1 | 18 | 1.4 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 19 | 0 | 23 | 0 |
| Dyspnea | 14 | 1.7 | 17 | 3.5 |
| Eye disorders | ||||
| Ocular toxicity | 16 | 0.7 | 7 | 0 |
| Psychiatric disorders | ||||
| Insomnia | 10 | 0 | 11 | 0 |
Source: LAZCLUZE Prescribing Information
a Grouped terms
b Applicable only to amivantamab
Abbreviations: NSCLC, non-small cell lung cancer
Were there any differences in side effects among sex, race, and age?
- Sex: The occurrence of side effects was similar between males and females.
- Race: The occurrence of side effects was similar between Asians and patients of other races.
- Age: No overall differences in safety were observed between patients younger and older than 65 years of age.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Table 5. Side Effects by Subgroup, Safety Population
| Subgroup | All Grades % | Grade ≥3 % |
|---|---|---|
| Age, years | ||
| <65 | 100 | 71 |
| ≥65 | 100 | 81 |
| Sex | ||
| Male | 100 | 74 |
| Female | 100 | 76 |
| Race | ||
| Asian | 100 | 71 |
| Other1 | 100 | 81 |
Source: Adapted from FDA Review
1 Other includes: White, Black or African American, American Indian or Alaska Native, Native Hawaiian or other Pacific Islander, multiple race, and unknown race
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.