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LAZCLUZE® (lazertinib)
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RYBREVANT FASPRO, LAZCLUZE - COPERNICUS Study

Last Updated: 05/31/2026

SUMMARY

  • RYBREVANT FASPRO for subcutaneous (SC) administration is a coformulation of amivantamab with recombinant human hyaluronidase PH20 (rHuPH20).1
  • LAZCLUZE (lazertinib) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI).2
  • COPERNICUS (NCT06667076) is an ongoing, phase 2b, open-label study evaluating the efficacy and safety of RYBREVANT FASPRO in combination with LAZCLUZE as first-line (1L) treatment or in combination with platinum-based chemotherapy as second-line (2L) treatment, along with prophylactic supportive care measures for adverse events (AEs), in patients with common EGFR-mutated (EGFRm; Exon 19 deletion or Exon 21 L858R substitution) locally advanced or metastatic non-small cell lung cancer (NSCLC). The primary endpoint is the investigator-assessed progression free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Enrollment is planned for approximately 480 patients.1,3,4
  • Cohort 15:
  • Cohort 26:
    • Results were reported from a protocol-specified interim analysis of RYBREVANT FASPRO administered every 3 weeks (Q3W) plus chemotherapy as 2L treatment in patients with common EGFRm advanced NSCLC, who experienced disease progression on or after EGFR TKI monotherapy, and also received enhanced dermatologic AE prophylaxis.
      • At the clinical data cutoff date of March 16, 2026, cohort 2 included 29 patients enrolled in the US (see Table: Baseline Demographics and Clinical Characteristics in Cohort 2).
      • The median investigator-assessed PFS was 10.4 months (95% confidence interval [CI], 4.8-not estimable [NE]). Key secondary outcomes are presented in Table: Efficacy Outcomes in Cohort 2.
      • AEs were mostly grade 1-2, with no new safety signals identified (see Table: Summary of TEAEs in Cohort 2).
        • With enhanced dermatologic prophylaxis, rash (preferred term) was reported in 21% of patients, with no grade ≥3 events; in MARIPOSA-2, the incidence was 43% (grade ≥3, 6%).
        • Two patients experienced VTE (grade 2, n=1; grade 3, n=1); in MARIPOSA-2, VTE was reported in 13 patients (grade ≥3, n=3).

PRODUCT LABELING

ONGOING clinical study

COPERNICUS Study

Study Design/Methods

  • Ongoing, phase 2b, open-label study evaluating the efficacy and safety of RYBREVANT FASPRO in combination with LAZCLUZE as 1L treatment (cohort 1), or in combination with platinum-based chemotherapy as 2L treatment (cohort 2), in patients with EGFR-mutated locally advanced or metastatic NSCLC.1,3,4 
  • The study design is shown in Figure: COPERNICUS Study Design.
  • Both cohorts will prophylactically receive enhanced dermatologic AE management, and cohort 1 will receive prophylactic anticoagulation for the first 4 months of treatment.1,4 The AE management strategy is shown in Figure: Prophylaxis for Dermatologic AEs and VTE.
    • Patients also have the option to receive the enhanced infusion-related reaction prophylactic regimen from the SKIPPirr study.1,4,7 
  • The following pragmatic measures are being used to eliminate potential barriers to patient enrollment4:
    • One cycle of chemotherapy is permitted while awaiting biopsy results.
    • Only chest scans are required. Scans of other locations are at the investigator’s discretion.
    • Assessment schedules are based on clinical practice.
    • Liquid biopsies are permitted for diagnosis.
    • Broader limits are permitted for organ function and blood count.

COPERNICUS Study Design1,3-6 

COPERNICUS (ClinicalTrials.gov Identifier: NCT06667076) enrollment period: December 2024 onwards; estimated study completion: May 23, 2029.
Abbreviations: 1L, first-line; 2L, second-line; AE, adverse event; ANC, absolute neutrophil count; AUC, area under the curve; BW; body weight; C, cycle; CBR, clinical benefit rate; CR, complete response; ctDNA, circulating tumor DNA; D, day; DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor; eGFR, estimated glomerular filtration rate; EMEA, Europe, Middle East, and Africa; Exon19del, exon 19 deletion; icORR, intracranial objective response rate; icPFS, intracranial progression-free survival; ILD, interstitial lung disease; IV, intravenous; NSCLC, non-small cell lung cancer; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PO, oral; PRO, patient-reported outcome; PR, partial response; QD, daily; Q3W, every 3 weeks; Q4W, every 4 weeks; RECIST, Response Evaluation Criteria in Solid Tumors; SC, subcutaneous; SD, stable disease; TKI, tyrosine kinase inhibitor; US, United States; VTE, venous thromboembolism.
aPer protocol, while patients with active, untreated brain metastases are excluded, patients with previously treated, stable, or asymptomatic brain metastases are permitted in cohort 1, and patients with any history of brain metastases (no indication for further local therapy) are permitted in cohort 2.
bIncluding but not limited to hypertension, diabetes, infection, impaired oxygenation, cardiovascular disease, etc.
cIn 28-day cycles until disease progression, withdrawal of consent, or the investigator decides to discontinue treatment, whichever comes first. Dosing (28-day cycles): amivantamab SC was administered as an abdominal injection at 1600 mg (2240 mg if BW ≥80 kg) weekly for the first 4 weeks, followed by 3520 mg (4640 mg if BW ≥80 kg) Q4W thereafter.
dIn 21-day cycles until disease progression, withdrawal of consent, or the investigator decides to discontinue treatment, whichever comes first. Dosing (21-day cycles): amivantamab SC was administered as an abdominal injection at 1600 mg (2240 mg if BW ≥80 kg) on C1D1, followed by 2400 mg (3360 mg if BW ≥80 kg) on days 8 and 15 of C1, and Q3W thereafter.
ePercentage of patients who achieved either a CR or PR per RECIST v1.1, as assessed by the investigator.
fPercentage of patients who achieved a CR, PR, or durable SD of ≥11 weeks’ duration per RECIST v1.1, as assessed by the investigator.
gThe real-world comparison will be assessed under a separate protocol.

Prophylaxis for Dermatologic AEs and VTE1,4-11

Abbreviations: AE, adverse event; ARR, administration-related reaction; BID, twice daily; ESMO, European Society for Medical Oncology; NCCN, National Comprehensive Cancer Network; VTE, venous thromboembolism.
aIncludes standard premedication (antihistamines, antipyretics, and glucocorticoids).
bProphylactic antibiotics: oral doxycycline or minocycline 100 mg BID and topical clindamycin lotion 1% on the scalp daily before bedtime. Paronychia prophylaxis: chlorhexidine 4% on the fingernails and toenails daily. Skin moisturization of the body and face at least daily.
cTacrolimus was added as a reactive management recommendation in COPERNICUS based on positive results from the COCOON treatment substudy. In addition, a protocol amendment for COPERNICUS recommended zinc supplementation for patients with established zinc deficinecy who experienced dermatologic AEs.
dLa Roche Posay Lipikar AP+M moisturizer was used in COCOON.

Results: RYBREVANT FASPRO Q4W Plus LAZCLUZE Along With VTE and Dermatologic AE Prophylaxis (Cohort 1)

  • Early results on patient demographics and safety were reported for RYBREVANT FASPRO administered Q4W plus LAZCLUZE as 1L treatment in US patients with common EGFRm advanced NSCLC who also received VTE and dermatologic AE prophylaxis.5
Patient Characteristics

Baseline Demographics and Clinical Characteristics in Cohort 15
Characteristic, n (%)
RYBREVANT FASPRO Q4W + LAZCLUZE
(n=235)
Age, median (range), years
66 (34-90)
   ≥65 years
131 (56)
   ≥75 years
50 (21)
Female
153 (65)
Race
   White
122 (52)
   Asian
62 (26)
   Black or African American
22 (9)
   Othera
29 (12)
Hispanic or Latino
29 (12)
ECOG PS score
   0
109 (46)
   1
126 (54)
History of smoking
74 (31)
Brain metastases at screening
90 (38)
EGFR mutation typeb
   Ex19del
141 (60)
   L858R
94 (40)
Received 1 cycle of chemotherapy prior to study enrollmentc
6 (3)
Abbreviations: ECOG PS, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor; Ex19del, Exon 19 deletion; L858R, Exon 21 L858R substitution; Q4W, every 4 weeks.
aIncludes American Indian or Alaska Native (<1%), Native Hawaiian or other Pacific Islander (<1%), unknown (5%), and not reported (6%).
bPatients may have both Ex19del and L858R.
cIncludes adjuvant (17%), curative/palliative/any other intent (50%), and neoadjuvant (33%).
Safety
  • AEs were mostly grade 1-2, with no new safety signals identified (see Table: Summary of TEAEs in Cohort 1).5
  • Eighteen patients (8%) discontinued RYBREVANT FASPRO due to AEs; of those, 14 patients (6% of the total cohort) discontinued due to treatment-related AEs.5

Summary of TEAEs in Cohort 15
TEAEs (≥20%) by Preferred Term, n (%)
RYBREVANT FASPRO Q4W + LAZCLUZE
(n=235)
All Grades
Grade ≥3
EGFR-related
   Fatigue
98 (42)
9 (4)
   Dermatitis acneiform
82 (35)
9 (4)
   Stomatitis
79 (34)
7 (3)
   Paronychia
77 (33)
6 (3)
   Diarrhea
68 (29)
4 (2)
   Rash
56 (24)
10 (4)
   Pruritus
51 (22)
1 (<1)
MET-related
   Peripheral edema
79 (34)
4 (2)
   Hypoalbuminemia
69 (29)
10 (4)
Other
   Nausea
94 (40)
2 (<1)
   Constipation
60 (26)
0
   Increased ALT
55 (23)
11 (5)
   Decreased appetite
49 (21)
1 (<1)
   Myalgia
48 (20)
0
Abbreviations: ALT, alanine aminotransferase; EGFR, epidermal growth factor receptor; MET, mesenchymal-epithelial transition; Q4W, every 4 weeks; TEAE, treatment-emergent adverse event.

TEAEs of Interest in COPERNICUS Cohort 1 and MARIPOSA (median follow-up, 22 months)5
TEAEs of Interest, %
COPERNICUS Cohort 1
(n=235)
MARIPOSA
(n=421)
Grade 1-2
Grade ≥3
Grade 1-2
Grade ≥3
Paronychiaa
33
3
68
11
Rasha
24
4
62
15
VTEb
9
2
37
11
ARRb,c/IRRa,c
0.9
0
63
6
Note: No formal, head-to-head statistical comparison was performed. Because follow-up in COPERNICUS is limited, these results are presented for contextual reference only and should not be used for direct comparison.Abbreviations: ARR, administration-related reaction; IRR, infusion-related reaction; TEAE, treatment-emergent adverse event; VTE, venous thromboembolism.
aPreferred term.
bGrouped term.
cThe term ARR was used in COPERNICUS, and the term IRR was used in MARIPOSA.

TEAEs of Interest in COPERNICUS Cohort 1 and MARIPOSA (within 4 months of treatment)5
TEAEs of Interest, %
COPERNICUS Cohort 1
(n=159)
MARIPOSA
(n=421)
All Grades
Grade ≥3
All Grades
Grade ≥3
Paronychiaa
37
1
50
4
Rasha
25
3
55
7
VTEb
3
1
23
6
ARRb,c/IRRa,c
1
0
55
5
Note: No formal, head-to-head statistical comparison was performed. These results are presented for contextual reference only and should not be used for direct comparison.Abbreviations: ARR, administration-related reaction; IRR, infusion-related reaction; TEAE, treatment-emergent adverse event; VTE, venous thromboembolism.
aPreferred term.
bGrouped term.
cThe term ARR was used in COPERNICUS, and the term IRR was used in MARIPOSA.

Results: RYBREVANT FASPRO Q3W Plus Chemotherapy Along With Dermatologic AE Prophylaxis (Cohort 2)

Results were reported from a protocol-specified interim analysis of RYBREVANT FASPRO administered Q3W plus chemotherapy as 2L treatment in patients with common EGFRm advanced NSCLC, who experienced disease progression on or after EGFR TKI monotherapy, and also received enhanced dermatologic AE prophylaxis.6

Patient Characteristics

Baseline Demographics and Clinical Characteristics in Cohort 26
Characteristic, n (%)
RYBREVANT FASPRO Q3W + Chemotherapya
(n=29)
Age, median (range), years
62 (39-92)
   ≥65 years
13 (45)
   ≥75 years
6 (21)
Female
12 (41)
Race
   White
12 (41)
   Asian
11 (38)
   Black or African American
2 (7)
   Otherb
4 (14)
Hispanic or Latino
6 (21)
ECOG PS score
   0
11 (38)
   1
18 (62)
History of smoking
10 (34)
Brain metastases
8 (28)
EGFR mutation typec
   Ex19del
18 (62)
   L858R
11 (38)
Abbreviations: AUC, area under the curve; ECOG PS, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor; Ex19del, Exon 19 deletion; IV, intravenous; L858R, Exon 21 L858R substitution; Q3W, every 3 weeks.
aCarboplatin AUC 5 IV Q3W for upto 4 cycles + pemetrexed 500 mg/m2 IV Q3W.
bOther includes unknown (7%) and not reported (7%).
cPatients may have both Ex19del and L858R.
Efficacy

Efficacy Outcomes in Cohort 26
Outcome, n (%)
RYBREVANT FASPRO Q3W + Chemotherapya
(n=29)
Median investigator-assessed PFS, months (95% CI)
10.4 (4.8-NE)
Median OS, months (95% CI)
NE (11.2-NE)
Investigator-assessed ORR,b % (95% CI)
38 (21-58)
Best response,c n
   PR
11
   SD
13
   PD
2
CBR,d % (95% CI)
69 (49-85)
DCR,e % (95% CI)
83 (64-94)
Median DOR,f months (95% CI)
5.6 (2.8-NE)
   Responses lasting ≥6 months, %
18
Abbreviations: AUC, area under the curve; CBR, clinical benefit rate; CI, confidence interval; CR, complete response; DCR, disease control rate; DOR, duration of response; IV, intravenous; NE, not estimable; ORR, overall response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors; SD, stable disease; Q3W, every 3 weeks.
aCarboplatin AUC 5 IV Q3W for up to 4 cycles + pemetrexed 500 mg/m2 IV Q3W.
bPercentage of patients who achieved either a CR or PR per RECIST v1.1, as assessed by the investigator.
cThree response-evaluable patients with no evaluable target lesion measurements at any postbaseline disease evaluation assessments were not included.
dPercentage of patients who achieved a CR, PR, or durable SD of ≥11 weeks duration per RECIST v1.1, as assessed by the investigator.
ePercentage of patients who achieved a CR, PR, or SD, regardless of durability of stabilization, per RECIST v1.1, as assessed by the investigator.
fAmong responders.
Safety
  • AEs were mostly grade 1-2, with no new safety signals identified (see Table: Summary of TEAEs in Cohort 2).6
  • Overall, 38% of patients interrupted RYBREVANT FASPRO due to AEs; of those, 6 patients (21% of the total cohort) interrupted due to treatment-related AEs.6

Summary of TEAEs in Cohort 26
TEAEs (≥30%) by Preferred Term, n (%)
RYBREVANT FASPRO Q3W + Chemotherapya
(n=29)
All Grades
Grade ≥3
EGFR-related
   Fatigue
22 (76)
1 (3)
   Dermatitis acneiform
11 (38)
2 (7)
   Paronychia
9 (31)
0
MET-related
   Peripheral edema
9 (31)
0
   Hypoalbuminemia
9 (31)
0
Chemotherapy-related
   Neutropenia
12 (41)
5 (17)
   Leukopenia
11 (38)
5 (17)
   Anemia
9 (31)
2 (7)
   Thrombocytopenia
9 (31)
2 (7)
Other
   Nausea
16 (55)
1 (3)
   Constipation
14 (48)
0
   Decreased appetite
11 (38)
0
   Hypokalemia
10 (34)
0
Abbreviations: AUC, area under the curve; EGFR, epidermal growth factor receptor; IV, intravenous; MET, mesenchymal-epithelial transition; Q3W, every 3 weeks; TEAE, treatment-emergent adverse event.
aCarboplatin AUC 5 IV Q3W for upto 4 cycles + pemetrexed 500 mg/m2 IV Q3W.
  • With enhanced dermatologic prophylaxis, rash (preferred term) was reported in 21% of patients, with no grade ≥3 events; in MARIPOSA-2, the incidence was 43% (grade ≥3, 6%).6
  • No patients experienced ARR; in MARIPOSA-2, the incidence of infusion-related reactions (IRRs) was 58% (grade ≥3, 5%).6
  • Two patients experienced VTE (grade 2, n=1; grade 3, n=1); in MARIPOSA-2, VTE was reported in 13 patients (grade ≥3, n=3).6
  • Grade ≥3 neutropenia occurred in 17% of patients, which is consistent with previous observations with carboplatin-pemetrexed use.6
    • Two patients interrupted RYBREVANT FASPRO due to neutropenia.

Literature Search

A literature search of MEDLINE®, Embase®, BIOSIS Previews®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 28 May 2026.

 

References

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1 Halmos B, Florez N, Goldberg S, et al. A phase 2b study of subcutaneous amivantamab with lazertinib as first-line treatment, or with chemotherapy as second-line treatment, for EGFR-mutated non-small cell lung cancer (NSCLC): COPERNICUS. Poster presented at: American Association for Cancer Research (AACR) Annual Meeting; April 25-30, 2025; Chicago, IL.  
2 Cho BC, Felip E, Hayashi H, et al. MARIPOSA: phase 3 study of first-line amivantamab + lazertinib versus osimertinib in EGFR-mutant non-small-cell lung cancer. Future Oncol. 2022;18(6):639-647.  
3 Janssen Research & Development, LLC. A phase 2b, open-label, two-cohort study of subcutaneous amivantamab in combination with lazertinib as first-line treatment, or subcutaneous amivantamab in combination with platinum-based chemotherapy as second-line treatment, for common EGFR-mutated locally advanced or metastatic non-small cell lung cancer. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2026 May 28]. Available from: https://clinicaltrials.gov/study/NCT06667076 NLM Identifier: NCT06667076.  
4 Halmos B, Florez N, Goldberg S, et al. COPERNICUS: a multinational pragmatic phase 2 trial of subcutaneous amivantamab in common EGFR-mutated NSCLC. e-Poster available at: European Society for Medical Oncology (ESMO) Congress; October 17-21, 2025; Berlin, Germany.  
5 Goldberg SB, Halmos B, Florez N, et al. COPERNICUS, a pragmatic phase 2b study of first-line subcutaneous amivantamab + lazertinib with supportive care in EGFR-mutated advanced NSCLC: early safety results. Poster presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; May 29-June 2, 2026; Chicago, IL.  
6 Leal T, Halmos B, Florez N, et al. COPERNICUS, a pragmatic phase 2b study of subcutaneous amivantamab plus chemotherapy with enhanced dermatologic adverse event prophylaxis in EFGR-mutated advanced NSCLC: interim results. Poster presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; May 29-June 2, 2026; Chicago, IL.  
7 Spira AI, Paz-Ares L, Han JY, et al. Preventing infusion-related reactions with intravenous amivantamab-results from SKIPPirr, a phase 2 study: a brief report. J Thorac Oncol. 2025;20(6):809-816.  
8 Leighl NB, Akamatsu H, Lim SM, et al. Subcutaneous versus intravenous amivantamab, both in combination with lazertinib, in refractory epidermal growth factor receptor-mutated non-small cell lung cancer: primary results from the phase III PALOMA-3 study. J Clin Oncol. 2024;42(30):3593-3605.  
9 Lim SM, Tan JL, Dias JM, et al. Subcutaneous amivantamab and lazertinib as first-line treatment in patients with mutated advanced non-small cell lung cancer (NSCLC): interim results from the phase 2 PALOMA-2 study. Poster presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; May 31-June 4, 2024; Chicago, IL.  
10 Cho BC, Li W, Spira AI, et al. Enhanced versus standard dermatologic management with amivantamab-lazertinib in EGFR-mutated advanced NSCLC: the COCOON global randomized controlled trial. J Thorac Oncol. 2025;20(10):1517-1530.  
11 Cho BC, Li W, Spira AI, et al. Supplementary appendix for: Enhanced versus standard dermatologic management with amivantamab-lazertinib in EGFR-mutated advanced NSCLC: the COCOON global randomized controlled trial. J Thorac Oncol. 2025;20(10):1517-1530.  

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