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RYBREVANT®

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RYBREVANT® (amivantamab-vmjw)

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Amivantamab SC, RYBREVANT, LAZCLUZE - PALOMA-2 study

Last updated: 10/17/2025
  • RYBREVANT (amivantamab-vmjw) is a low fucose, fully human IgG1-based bispecific antibody with immune cell-directing activity that targets EGFR mutations and MET mutations and amplifications in NSCLC.1
  • Amivantamab for SC administration is a coformulation of amivantamab with rHuPH20.2
  • LAZCLUZE (lazertinib) is a third-generation EGFR tyrosine kinase inhibitor.3

PALOMA-2 study

  • PALOMA-2 (NCT05498428) is an ongoing, phase 2, open-label, international, parallel-cohort study evaluating the efficacy and safety of a SC formulation of amivantamab with chemotherapy and/or LAZCLUZE in patients with EGFR-mutated advanced NSCLC (N=520). The primary endpoint is investigator-assessed ORR.4-8

Cohorts 1 and 6

  • Interim efficacy, safety, and PK results were reported for amivantamab SC plus LAZCLUZE with either recommended (cohort 1, n=68) or mandatory (cohort 6, n=58) prophylactic anticoagulation in treatment-naïve patients with EGFR-mutated (Exon19del or Exon 21 L858R) advanced NSCLC.4
    • At a median follow-up of 8.6 months, the investigator-assessed ORR was 75% (95% CI, 63-85) in cohort 1 and 80% (95% CI, 65-90) in cohort 6.
    • The most common TEAEs (≥20%) were associated with EGFR and MET inhibition and were primarily grade 1-2 in severity.
    • The ARR (MedDRA preferred term) rate was 15% in all patients.
    • The VTE rate was 18% in cohort 1 and 7% in cohort 6.
    • TRAEs leading to discontinuation of all agents were reported in 9% of patients.
    • Mean (%CV) amivantamab coformulation Ctrough on C2D1 were 328 (32) µg/mL in cohort 1 and 373 (27) µg/mL in cohort 6.

Cohort 2

  • Efficacy, safety, and PK results were reported for amivantamab SC plus chemotherapy in treatment-naïve patients with EGFR Exon20ins-mutated advanced NSCLC (n=66).6
    • At a median follow-up of 10.4 months, the investigator-assessed ORR was 76% (95% CI, 64-86).
    • The most common TEAEs (≥25%) were associated with EGFR and MET inhibition and were primarily grade 1-2 in severity.
    • The ARR (MedDRA preferred term) rate was 6% in all patients.
    • TRAEs leading to discontinuation of amivantamab SC were reported in 12% of patients.
    • Mean (%CV) amivantamab plasma concentration on C2D1 was 439 (27) µg/mL.

Cohort 3b

  • Efficacy, safety, and PK results were reported for amivantamab SC plus chemotherapy in patients with EGFR-mutated (Exon19del or Exon 21 L858R) advanced NSCLC after disease progression on osimertinib (n=77).8
    • At a median follow-up of 7 months, the investigator-assessed ORR was 47% (95% CI, 35-59).
    • The most common TEAEs (≥20%) were associated with EGFR and MET inhibition and were primarily grade 1-2 in severity.
    • The ARR (MedDRA preferred term) rate was 8% in all patients.
    • TRAEs leading to discontinuation of amivantamab SC were reported in 5% of patients.
    • Mean (%CV) amivantamab plasma concentration on C2D1 was 469 (26) µg/mL.

Note: ARR, administration-related reaction; C, cycle; CI, confidence interval; Ctrough, trough concentration; CV, coefficient of variation; D, day; EGFR, epidermal growth factor receptor; Exon19del, Exon 19 deletion; Exon20ins, Exon 20 insertion; IgG1, immunoglobulin G1; MedDRA, Medical Dictionary for Regulatory Activities; MET, mesenchymal-epithelial transition; NSCLC, non-small cell lung cancer; ORR, objective response rate; PK, pharmacokinetics; rHuPH20, recombinant human hyaluronidase PH20; SC, subcutaneous; TEAE, treatment-emergent adverse event; VTE, venous thromboembolism.

Cohort 4

  • Initial safety and PK results were reported for patients switching from RYBREVANT IV to amivantamab SC. Patients in cohort 4 previously received RYBREVANT IV for ≥8 weeks without dose reduction or evidence of PD, as part of standard of care, an expanded access program, or rollover from a long-term extension study.9
    • At a median follow-up of 9.7 months, the safety profile of amivantamab SC after switching from RYBREVANT IV was consistent with previous reports of amivantamab SC monotherapy, with no new safety signals; no ARRs were reported.
    • The most common AEs associated with EGFR and MET inhibition were paronychia (44%) and hypoalbuminemia (40%), respectively.
    • The simulated PK exposures of amivantamab IV were noninferior to amivantamab SC for the Q2W dose regimen, meeting the predefined noninferiority criteria for efficacy (lower bound of the GMR 90% CI ≥0.8 for Cavg and Ctrough) and safety (upper bound of the GMR 90% CI ≤1.25 for Cmax).
    • Most patients receiving amivantamab SC by C1 were satisfied (79%), found it convenient (83%), and preferred it (63%) over RYBREVANT IV.

Cohort 5

  • Efficacy, safety, and PK results were reported for amivantamab SC plus LAZCLUZE in treatment-naïve patients with EGFR-mutated (Exon19del or Exon 21 L858R) advanced NSCLC (n=77).7
    • At a median follow-up of 6.5 months, the investigator-assessed ORR was 82% (95% CI, 71–90).
    • The most common TEAEs (≥20%) were associated with EGFR and MET inhibition and were primarily grade 1-2 in severity.
    • The ARR (MedDRA preferred term) rate was 12% in all patients.
    • TRAEs leading to discontinuation of all agents were reported in 8% of patients.
    • Mean (%CV) amivantamab plasma concentration on C2D1 was 366 (31) µg/mL.

Cohort 7

  • Cohort 7 is evaluating the efficacy and safety of amivantamab SC plus chemotherapy after first-line RYBREVANT plus LAZCLUZE in patients with EGFR-mutated (Exon19del or Exon 21 L858R) advanced NSCLC.7
  • At a median follow-up of 3.6 months, 10 patients who had disease progression on RYBREVANT plus LAZCLUZE have received amivantamab SC plus chemotherapy.7
    • The ORR was 50% among the 8 response evaluable patients.
    • Early safety profile was consistent with prior report of amivantamab SC plus chemotherapy.

Note: AE, adverse event; ARR, administration-related reaction; C, cycle; Cavg, average concentration; Cmax, maximum concentration; CI, confidence interval; Ctrough, trough concentration; CV, coefficient of variation; D, day; EGFR, epidermal growth factor receptor; Exon19del, Exon 19 deletion; GMR, geometric mean ratio; IV, intravenous; MedDRA, Medical Dictionary for Regulatory Activities; MET, mesenchymal-epithelial transition; NSCLC, non-small cell lung cancer; ORR, objective response rate; PD, progressive disease; PK, pharmacokinetics; Q2W, every 2 weeks; SC, subcutaneous; TEAE, treatment-emergent adverse event; TRAE, treatment-related adverse event.

Overview4-9

PALOMA-2 (NCT05498428) is an ongoing, phase 2, open-label, international, parallel-cohort study designed to assess the efficacy and safety of amivantamab SC with chemotherapy and/or LAZCLUZE in patients with EGFR-mutated advanced NSCLC.

Key inclusion criteria4-9

  • Adults (age ≥18 years) with locally advanced or metastatic NSCLC
  • ≥1 measurable lesion per RECIST v1.1 (all cohorts except cohort 4)
  • ECOG PS 0 or 1
  • Brain metastases if present must be stablea
  • Adequate organ functions

Study design4-9

Efficacy results4,6-8

Cohorts 1 and 64

INV- and ICR-assessed ORR (confirmed and unconfirmed responses)

Endpoint Cohort 1
(n=68) 		Cohort 6
(n=45) 		Overall
(N=113)
INV ICR INV ICR INV ICR
ORR, % (95% CI) 75 (63- 85) 81 (70 -89) 80 (65 -90) 76 (61 -87) 77 (68 -84) 79 (70 -86)

Median follow-up was 10 months for cohort 1, 6.1 months for cohort 6, and 8.6 months overall.

Cohort 2 (n=66)6

  • The INV- and ICR-assessed ORR was 76% (95% CI, 64-86) and 77% (95% CI, 65-87), respectively.

Cohort 3b (n=77)8

  • The INV- and ICR-assessed ORR was 47% (95% CI, 35-59) and 53% (95% CI, 42-65), respectively.

Cohort 5 (n=77)7

  • The INV- and ICR-assessed ORR was 82% (95% CI, 71–90) and 87% (95% CI, 77–94), respectively.

Cohort 7 (n=10)7

  • The ORR was 50% among the 8 response evaluable patients.

Safety results4,6-9

Cohorts 1 (n=68) and 6 (n=57)4

  • The most common TEAEs (≥20%) were associated with EGFR and MET inhibition and were primarily grade 1-2 in severity.
  • ARRs were reported in 15% (19/125) of patients, with 90% reported in C1 (on or after C1D1 but before the next dose).
  • Median time to ARR onset (defined as the start of ARR minus the start of the last injection prior to this event) was 2.3 hours (range, 0.3-7.2).
  • TRAEs leading to the discontinuation of all agents were reported in 9% (11/125) of patients.

Cohort 2 (n=66)6

  • The most common TEAEs (≥25%) were associated with EGFR and MET inhibition and were primarily grade 1-2 in severity.
  • ARRs were reported in 4 (6%) patients in C1 (on or after C1D1 but before the next dose).
  • Median time to ARR onset was 1.6 hours (range, 0.7-2.4).
  • TRAEs leading to the discontinuation of amivantamab SC were reported in 12% of patients.

Cohort 3b (n=77)8

  • The most common TEAEs (≥20%) were associated with EGFR and MET inhibition and were primarily grade 1-2 in severity.
  • ARRs were reported in 6 (8%) patients in C1 (all the ARRs were reported and were resolved in C1D1).
  • Median time to ARR onset was 2.7 hours (range, 1.1-6.3).
  • TRAEs leading to the discontinuation of amivantamab SC were reported in 5% of patients.

Cohort 4 (n=25)9

  • The most common AEs associated with EGFR and MET inhibition were paronychia (44%) and hypoalbuminemia (40%), respectively.
  • TRAE (interstitial lung disease) leading to discontinuation of amivantamab SC was reported in 1 patient.
  • No ARRs were reported.

Cohort 5 (n=77)7

  • The most common TEAEs (≥20%) were associated with EGFR and MET inhibition and were primarily grade 1-2 in severity.
  • ARRs were reported in 9 (12%) patients, with 78% reported in C1 (on or after C1D1 but before the next dose).
  • TRAEs leading to the discontinuation of all agents were reported in 8% of patients.

Cohort 7 (n=10)7

  • Early safety profile was consistent with prior report of amivantamab SC plus chemotherapy.

PK4,6-9

Cohorts 1 (n=50) and 6 (n=42)4

  • Consistent with historic RYBREVANT IV levels, mean (%CV) amivantamab coformulation Ctrough concentrations on C2D1 were as follows:
  • Cohort 1 (n=50): 328 (32) µg/mL
  • Cohort 6 (n=42): 373 (27) µg/mL

Cohort 26

  • Consistent with historic RYBREVANT IV Q3W data, mean (%CV) amivantamab plasma concentration on C2D1 was 439 (27) µg/mL (n=41).

Cohort 3b8

  • Consistent with historic RYBREVANT IV Q3W data, mean (%CV) amivantamab plasma concentration on C2D1 was 469 (26) µg/mL (n=42).

Cohort 49

  • The PK exposures of amivantamab IV were noninferior to amivantamab SC for the Q2W dose regimen, meeting the predefine noninferiority criteria for efficacy (lower bound of the GMR 90% CI ≥0.8 for Cavg and Ctrough) and safety (upper bound of the GMR 90% CI ≤1.25 for Cmax).

Cohort 57

  • Consistent with historic RYBREVANT IV and SC Q2W data, mean (%CV) amivantamab plasma concentration on C2D1 was 366 (31) µg/mL (n=56).

Note: AE, adverse event; ARR, administration-related reaction; C, cycle; Cavg, average concentration; Cmax, maximum concentration; CI, confidence interval; Ctrough, trough concentration; CV, coefficient of variation; D, day; ECOG PS, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor; Exon19del, Exon 19 deletion; Exon20ins, Exon 20 insertion; GMR, geometric mean ratio; ICR, independent central review; INV, investigator; IV, intravenous; MET, mesenchymal-epithelial transition; NSCLC, non-small cell lung cancer; ORR, objective response rate; PK, pharmacokinetics; PO, orally; Q2W, every 2 weeks; Q3W, every 3 weeks; Q4W, every 4 weeks; QD, once daily; RECIST v1.1, Response Evaluation Criteria in Solid Tumors version 1.1; SC, subcutaneous; SC-CF, subcutaneous coformulation with recombinant human hyaluronidase PH20; TEAE, treatment-emergent adverse event; TRAE, treatment-related adverse event; US, United States.

  • PALOMA-2 (NCT05498428) is an ongoing, phase 2, open-label, international, parallel-cohort study designed to assess the efficacy and safety of amivantamab SC with chemotherapy and/or LAZCLUZE in patients with EGFR-mutated advanced NSCLC.4,5
  • Amivantamab SC, coformulated with rHuPH20, is administered by manual injection in the abdomen.4-8

PALOMA-2 study design4-9

PALOMA-2 (ClinicalTrials.gov Identifier: NCT05498428); data cutoff date: January 6, 2024.
aIncludes asymptomatic or previously treated patients with stable brain metastases.
bReceived first-line regimen.
c1600 mg (2240 mg if BW ≥80 kg) QW on C1D1, C1D8, C1D15, and C1D22, then Q2W on D1 and D15 of each subsequent 28-day cycle starting with C2.
d1600 mg (2240 mg if BW ≥80 kg) on C1D1, then 2400 mg (3360 mg if BW ≥80 kg) on C1D8 and C1D15 and D1 of each subsequent 21-day cycle starting with C2.
eCarboplatin AUC5 (for a maximum of 4 cycles) and pemetrexed 500 mg/m2 until disease progression on D1 of each cycle.
fExperienced disease progression on or after osimertinib treatment.
gStarting C5D1.
hPatients previously received amivantamab IV 1050 mg (1400 mg if BW ≥80 kg) for ≥8 weeks without dose reduction or evidence of PD, as part of standard of care, an expanded access program, or rollover from a long-term extension study.
iAmivantamab SC-CF induction with 1600 mg (2240 mg if BW ≥80 kg) on C1D1, C1D8, C1D15, and C1D22, then starting with C2D1 of each next 28-day cycle, amivantamab SC-CF (160 mg/mL co-formulated with rHuPH20) by manual injection at 3520 mg (4640 mg if BW ≥80 kg).
jStarting C1D1.
kExperienced disease progression on or after amivantamab plus lazertinib.
lPer RECIST v1.1
mClinical benefit rate was defined as confirmed response or stable disease for ≥11 weeks.
nFor cohort 4, results were based on the resimulation of the PALOMA-3 study using the final population PK model, in which patients received amivantamab IV or SC at DL0, DL(-1), and DL(-2); PK samples were not collected in PALOMA-2 cohort 4.
oTreatment satisfaction was assessed using the mTASQ, a 12-item questionnaire measuring the impact of treatment mode (SC administration) on physical functioning; psychological functioning; and activities of daily living, convenience, and satisfaction. Assessment was performed at screening (before amivantamab IV to SC switch) and after amivantamab SC administration at C1D1, C3D1, and EOT. The modified questionnaire specifies that the injection will take place in the “skin.”

  • Interim efficacy, safety, and PK results were reported for amivantamab SC plus LAZCLUZE with either recommended (cohort 1) or mandatory (cohort 6) prophylactic anticoagulation in treatment-naïve patients with EGFR-mutated (Exon19del or Exon 21 L858R) advanced NSCLC.4

Demographics and baseline disease characteristics4

Characteristic Characteristic Cohort 1
(n=68) 		Cohort 6
(n=58) 		Total
(n=126)
Median age, years (range) 58 (28-85) 62 (34-83) 59 (28-85)
Female, n (%) 42 (62) 34 (59) 76 (60)
Race, n (%)
Asian 45 (66) 40 (69) 85 (67)
White 19 (28) 16 (28) 35 (28)
Othera 4 (6) 2 (3) 6 (5)
ECOG PS 1, n (%) 48 (71) 43 (75) 91 (72)
History of smoking, n (%) 15 (22) 18 (31) 33 (26)
History of brain metastases, n (%) 20 (29) 18 (31) 38 (30)
EGFR mutation,b n (%)
Exon19del 45 (66) 34 (59) 79 (63)
Exon 21 L858R 24 (35) 24 (41) 48 (38)
Adenocarcinoma subtype, n (%) 65 (96) 57 (98) 122 (97)

aIncludes Black or African American and American Indian/Alaska Native.
bPatients could be included in >1 category.

Primary endpoint

  • At a median follow-up of 8.6 months, the investigator-assessed ORR with amivantamab SC plus LAZCLUZE was 77% (95% CI, 68-84) for both cohorts 1 and 6.4
    • In cohort 1 (median follow-up, 10 months; n=68) and cohort 6 (median follow-up, 6.1 months; n=45), the investigator-assessed ORR was 75% (95% CI, 63-85) and 80% (95% CI, 65-90), respectively.

Secondary endpoints

  • The ICR-assessed ORR reported with amivantamab SC plus LAZCLUZE was comparable with previous reports of RYBREVANT IV plus LAZCLUZE.4
    • The overall ICR-assessed ORR was 79% (95% CI, 70-86; cohort 1, 81% [95% CI, 70-89]; cohort 6, 76% [95% CI, 61-87]).
  • The investigator-assessed best response, TTR, and DOR in confirmed responders were evaluated across cohorts 1 and 6.4

Investigator-assessed best response, TTR, and DOR4

Parameters Cohorts 1 and 6
(n=111)
Best response,a n
CR 0
PR 75
SD 33
PD 2
Median TTR,b months (range) 1.9 (1.4-5.3)
Median DOR,a,b months NE

aPatients without postbaseline tumor assessment were excluded.
bAmong confirmed responders (n=75).

  • AEs reported with amivantamab SC plus LAZCLUZE were consistent with previous reports of RYBREVANT IV plus LAZCLUZE. The most common TEAEs (≥20%) were associated with EGFR and MET inhibition and were primarily grade 1-2 in severity.4
  • ARRs were reported in 15% (19/125) of patients.4
    • ARRs (90%; 18/20) were mostly reported in C1 (on or after C1D1 but before the next dose).
    • One patient reported 2 ARRs (1 on C1D1 and 1 on C1D9).
    • Median time to ARR onset (defined as the start of ARR minus the start of the last injection prior to this event) was 2.3 hours (range, 0.3-7.2).
  • TRAEs leading to the discontinuation of all agents were reported in 9% (11/125) of patients.4
  • In the safety-evaluable set, 48 (71%) patients in cohort 1 and 57 (100%) patients in cohort 6 received prophylactic anticoagulation (apixaban, rivaroxaban, dalteparin, or enoxaparin as included in the national treatment guidelines; please refer to individual product labels for complete Prescribing Information).4
  • VTE was reported in 13% (16/125) of all patients, with 18% (12/68) in cohort 1 and 7% (4/57) in cohort 6.4
    • Most VTEs were grade 1-2 in severity; no grade 5 events were reported.
    • No VTEs led to dose reductions.
  • Of the 12 patients in the prophylactic anticoagulation group who reported VTE, 11 (92%) reported VTE after receiving prophylactic anticoagulation.4
    • Median onset time of VTE after discontinuing prophylactic anticoagulation was 70 days (range, 2-185).

VTE and bleeding events based on prophylactic anticoagulation use4

n (%) Any prophylactic
anticoagulation
(n=105) 		No prophylactic
anticoagulation
(n=20) 		Total
(n=125)
Any VTEa 12 (11) 4 (20) 16 (13)
Grade ≥3 0 1 (5) 1 (1)
Grade 5 0 0 0
Any VTE leading to death 0 0 0
Any VTE leading to any discontinuation 0 0 0
Grade ≥3 bleedingb 2 (2)c 0 2 (2)

aVTE AEs were identified using the SMQ for “Embolic and Thrombotic events, Venous (SMQ),” and the preferred term was “Thrombosis” or “Embolism.”
bBleeding AE terms were identified using the SMQ for “Hemorrhage Terms (Excl Laboratory Terms)” (narrow scope).
cOne patient had been on rivaroxaban 10 mg PO daily since D1 and developed chronic pigmented purpura on D67, which resolved on D79; another patient had been on rivaroxaban 10 mg PO daily since D1 and developed grade 3 subarachnoid hemorrhage on D76, which remained unresolved.

  • Consistent with historic RYBREVANT IV levels, mean (% CV) amivantamab coformulation Ctrough on C2D1 were as follows4:
    • Cohort 1 (n=50): 328 (32) µg/mL
    • Cohort 6 (n=42): 373 (27) µg/mL
  • Efficacy, safety, and PK results were reported for amivantamab SC plus chemotherapy in treatment-naïve patients with EGFR Exon20ins-mutated advanced NSCLC (cohort 2).6
  • At the data cutoff of October 24, 20246:
    • Median follow-up was 10.4 months.
    • Median treatment duration was 9.3 months.
    • In total, 37 (56%) patients remained on treatment.

Demographics and baseline disease characteristics6

Characteristic Cohort 2
(n=66)
Median age, years (range) 63 (31-80)
Male, n (%) 34 (52)
Race, n (%)
Asian 37 (56)
White 27 (41)
Othera 2 (3)
ECOG PS 1, n (%) 42 (64)
History of smoking, n (%) 24 (36)
History of brain metastases, n (%) 24 (36)
EGFR mutation,b n (%)
Exon20ins 66 (100)
Exon19del 1 (2)
Exon 21 L858R 1 (2)
Adenocarcinoma histology, n (%) 64 (97)

aIncludes Black or African American and Native Hawaiian/Other Pacific Islander.
bPatients could be included in >1 category.

Primary endpoint

  • The investigator-assessed ORR and the confirmed investigator-assessed ORR with amivantamab SC plus chemotherapy was 76% (95% CI, 64-86) and 71% (95% CI, 59-82), respectively.6

Secondary endpoints

  • The ICR-assessed ORR reported with amivantamab SC plus chemotherapy was comparable with previous reports of RYBREVANT IV Q3W plus chemotherapy.6
    • The ICR-assessed ORR and the confirmed ICR-assessed ORR was 77% (95% CI, 65-87) and 67% (95% CI, 54-78), respectively.
  • The confirmed investigator-assessed and ICR-assessed CBR was 94% (95% CI, 85-98) and 89% (95% CI, 79-96), respectively.6
  • Among confirmed responders, majority of responses were ongoing (66% [31/47]), and 62% (29/47) of patients had a response duration of ≥6 months.6

Investigator-assessed best response, TTR, and DOR6

Parameters Cohort 2
(n=63)
Best response,a n
PR 47
SD 15
PD 1
Median TTR,b months (range) 6.4 (3.5-21.7)
Median DOR,b months (95% CI) 10.6 (8.3-NE)

aAmong patients with measurable disease at baseline.
bAmong confirmed responders (n=47).

  • Median PFS and OS was 12.2 months (95% CI, 8.4-NE) and NE (95% CI, 11.4-NE), respectively, consistent with previous reports of RYBREVANT IV Q3W plus chemotherapy.6
  • The most common TEAEs were EGFR/MET-related and hematologic. No new safety signals were identified.6
  • ARRs (defined per the MedDRA preferred term and referred to as infusion-related reactions in prior IV studies) were reported in 4 (6%) patients.6
    • All the ARRs were reported in C1 (on or after C1D1 but before the next dose)
    • No grade ≥3 ARRs were reported.
    • Median time to ARR onset was 1.6 hours (range, 0.7-2.4), and median duration of ARR was 7.2 hours (range, 0.3-14).
    • Rate of ARRs was 7-fold lower compared with previous reports of RYBREVANT IV Q3W plus chemotherapy.
  • TRAEs leading to discontinuation of amivantamab SC were reported in 12% of patients.6

Summary of AEs6

Most common TEAEs (≥25%), n (%) Cohort 2
(n=66)
All grades Grade ≥3
Associated with EGFR inhibition
Paronychia 45 (68) 3 (5)
Rash 30 (45) 6 (9)
Dermatitis acneiform 26 (39) 3 (5)
Stomatitis 24 (36) 4 (6)
Associated with MET inhibition
Hypoalbuminemia 36 (55) 7 (11)
Peripheral edema 27 (41) 1 (2)
Other
Neutropeniaa 33 (50) 19 (29)
Nausea 31 (47) 1 (2)
Anemia 30 (45) 10 (15)
Thrombocytopeniaa 27 (41) 9 (14)
Constipation 23 (35) 0
Increased ALT 21 (32) 1 (2)
Increased AST 19 (29) 1 (2)
Leukopenia 18 (27) 4 (6)
aDecreases in neutrophil and platelet counts were transient during C1, followed by recovery by C2D1 and stabilization thereafter.
  • Consistent with historic RYBREVANT IV Q3W data, mean (%CV) amivantamab plasma concentration on C2D1 was 439 (27) µg/mL (n=41).6
  • Efficacy, safety, and PK results were reported for amivantamab SC plus chemotherapy in patients with EGFR-mutated (Exon19del or Exon 21 L858R) advanced NSCLC after disease progression on osimertinib (cohort 3b).8
  • At the data cutoff of October 24, 20248:
    • Median follow-up was 7 months.
    • Median treatment duration was 6.2 months.
    • In total, 48 (62%) patients remained on treatment.

Demographics and baseline disease characteristics8

Characteristic Cohort 3b
(n=77)
Median age, years (range) 63 (41-77)
Female, n (%) 44 (57)
Race, n (%)
Asian 38 (49)
White 37 (48)
Black or African American 2 (3)
ECOG PS 1, n (%) 45 (58)
History of smoking, n (%) 27 (35)
History of brain metastases, n (%) 27 (35)
EGFR mutation,a n (%)
Exon19del 44 (57)
Exon 21 L858R 33 (43)

aPatients could be included in ≥1 category.

Primary endpoint

  • The investigator-assessed ORR and the confirmed investigator-assessed ORR with amivantamab SC plus chemotherapy was 47% (95% CI, 35-59) and 40% (95% CI, 29-52), respectively.8

Secondary endpoints

  • The investigator-assessed and ICR-assessed ORR reported with amivantamab SC plus chemotherapy was comparable with previous reports of RYBREVANT IV Q3W plus chemotherapy.8
    • The ICR-assessed ORR and the confirmed ICR-assessed ORR was 53% (95% CI, 42-65) and 52% (95% CI, 40-64), respectively
  • The confirmed investigator-assessed and ICR-assessed CBR was 84% (95% CI, 74-92) and 83% (95% CI, 73-91), respectively.8
  • Among confirmed responders, majority of responses were ongoing (71% [22/31]).8

Investigator-assessed best response, TTR, and DOR8

Parameters Cohort 3b
(n=75)
Best response,a n
PR 31
SD 38
PD 3
Median TTR,b weeks (range) 6.6 (5.2-17.8)
Median DOR,b months (95% CI) 6.3 (5.5-NE)

aPatients without a post-baseline tumor assessment were not included.
bAmong confirmed responders (n=31).

  • Median PFS was 7.9 months (95% CI, 6.8-NE), consistent with previous reports of RYBREVANT IV Q3W plus chemotherapy.8
  • Median OS was not estimable.8
  • The most common TEAEs were EGFR/MET-related and hematologic. No new safety signals were identified.8
  • ARRs (defined per the MedDRA preferred term and referred to as infusion-related reactions in prior IV studies) were reported in 6 (8%) patients.8
    • All the ARRs were reported and were resolved on C1D1.
    • No grade ≥3 ARRs were reported.
    • Median time to ARR onset was 2.7 hours (range, 1.1-6.3), and median duration of ARR was 2.7 hours (range, 0.1-6.1).
    • Rate of ARRs was ~7-fold lower compared with previous reports of RYBREVANT IV Q3W plus chemotherapy.
  • TRAEs leading to discontinuation of amivantamab SC were reported in 5% of patients.8

Summary of AEs8

TEAEs (≥20%) by preferred term, n (%) Cohort 3b
(n=77)
All grades Grade ≥3
Associated with EGFR inhibition
Paronychia 42 (55) 2 (3)
Rash 39 (51) 3 (4)
Stomatitis 27 (35) 3 (4)
Dermatitis acneiform 16 (21) 2 (3)
Associated with MET inhibition
Hypoalbuminemia 27 (35) 5 (6)
Peripheral edema 19 (25) 0
Other
Neutropeniaa 43 (56) 26 (34)
Nausea 35 (45) 2 (3)
Constipation 32 (42) 0
Thrombocytopeniaa 31 (40) 10 (13)
Anemia 27 (35) 5 (6)
Increased ALT 25 (32) 4 (5)
Decreased appetite 25 (32) 1 (1)
Leukopenia 24 (31) 12 (16)
Fatigue 22 (29) 4 (5)
Vomiting 20 (26) 6 (8)
Increased AST 20 (26) 3 (4)
Asthenia 16 (21) 2 (3)
aDecreases in neutrophil and platelet counts were transient during C1, followed by recovery by C2D1 and stabilization thereafter.
  • Consistent with historic RYBREVANT IV Q3W data, mean (%CV) amivantamab plasma concentration on C2D1 was 469 (26) µg/mL (n=42).8
  • Initial safety and PK results were reported for patients switching from RYBREVANT IV to amivantamab SC (cohort 4).9
  • Of the 26 patients enrolled in cohort 4, 25 were switched from RYBREVANT IV to amivantamab SC.9
  • At the data cutoff date of October 24, 20249:
    • Median follow-up from the first amivantamab SC dose was 9.7 months.
    • Median treatment duration was 3.1 months for prior RYBREVANT IV and 7.4 months for amivantamab SC.
    • In total, 64% of patients continued to receive amivantamab SC.

Demographics and baseline disease characteristics9

Characteristic Cohort 4
(n=26)
Median age, years (range) 66 (41-83)
Female, n (%) 15 (58)
Race, n (%)
Asian 14 (54)
White 10 (38)
Not reporteda 2 (8)
ECOG PS, n (%); n=25
0 9 (36)
1 16 (64)
History of smoking, n (%) 10 (38)
History of brain metastases, n (%) 8 (31)
EGFR mutation,b n (%); n=23
Exon 21 L858R 3 (13)
Exon20ins 21 (91)
Adenocarcinoma histology, n (%) 24 (92)

aPatient either declined to answer the question or was not able to identify a race.
bPatients could be included in ≥1 category.

  • The safety profile of amivantamab SC after switching from RYBREVANT IV was consistent with previous reports of amivantamab SC monotherapy, with no new safety signals reported.9
  • The most common AEs associated with EGFR and MET inhibition were paronychia (44%) and hypoalbuminemia (40%), respectively.9
  • The incidence of rash (grouped term, including rash, rash maculo-papular, acne, dermatitis acneiform, rash pustular, and skin lesions) was 40% (n=10), with grade ≥3 events reported in 12% of patients (n=3).9
  • TRAE (interstitial lung disease) leading to discontinuation of amivantamab SC was reported in 1 patient.9
  • No ARRs (defined per the MedDRA preferred term and referred to as infusion-related reactions in prior IV studies) were reported.9
  • Patient-reported treatment satisfaction was evaluated for RYBREVANT IV at screening vs amivantamab SC at C1.9

Patient-reported treatment satisfaction9

Patient responses to mTASQ, % RYBREVANT IV at screening
(n=25) 		Amivantamab SC at C1D1
(n=24)
Convenience over timea,b
Inconvenient or very inconvenient 24 0
Neither convenient nor inconvenient 32 17
Convenient or very convenient 44 83
Feeling restricted over timea,c
Quite a bit 4 0
A little bit or somewhat 72 46
Not at all 24 54
Bothered by the time it takes for infusion/injectiona,d
Quite bothered 28 0
A little or moderately bothered 60 33
Not at all bothered 12 67

aThe mTASQ for IV injection was completed at screening.
bBased on patient responses to mTASQ item #6, “How convenient is it for you to get your SC injection?”
cBased on patient responses to mTASQ item #5, “When receiving the SC injection, how restricted did you feel?”
dBased on patient responses to mTASQ item #7, “How bothered are you by the amount of time it takes to have the SC injection?”

PROs by C1

  • In total, 96% of patients were compliant with the mTASQ assessments.9
  • Most patients receiving amivantamab SC were satisfied (79%), found it convenient (83%), and preferred it (63%) over RYBREVANT IV.9
  • In total, 54% and 67% of patients receiving amivantamab SC (n=24) vs 24% and 12% receiving RYBREVANT IV (n=25), respectively, reported feeling unrestricted and unbothered by the time required for treatment administration.9
  • Most patients experienced mild or no injection-site symptoms with amivantamab SC9:
    • Mild or no pain: 71%
    • Mild or no swelling: 83%
    • Mild or no redness: 88%
  • Among patients receiving amivantamab SC, severe injection-site pain was reported in 8% at C1, with none reported at C3.9
  • Population PK simulations were conducted for amivantamab IV vs SC exposures for the Q2W dose regimen at DL0, DL(-1), and DL(-2).9
  • The simulated PK exposures of amivantamab IV were noninferior to amivantamab SC for the Q2W dose regimen, meeting the predefined noninferiority criteria for efficacy (lower bound of the GMR 90% CI ≥0.8 for Cavg and Ctrough) and safety (upper bound of the GMR 90% CI ≤1.25 for Cmax).9

PK simulations for the Q2W regimen9,a

PK endpoint Amivantamab IV (GM [CV%]) Amivantamab SC (GM [CV%]) SC/IV GMR (90% CI)
DL0 DL(-1) DL(-2) DL0 DL(-1) DL(-2) DL0 DL(-1) DL(-2)
Cavg,C2 362 (25) 229 (26) 98 (31) 396 (28) 245 (29) 148 (30) 1.09
(1.05-1.14) 		1.07
(1.03-1.12) 		1.52
(1.44-1.59)
Cavg,ss 245 (27) 148 (27) 57 (32) 275 (32) 160 (33) 89 (33) 1.12
(1.07-1.18) 		1.08
(1.03-1.14) 		1.56
(1.48-1.64)
Ctrough,max 305 (27) 191 (27) 80 (33) 367 (28) 227 (28) 138 (29) 1.2
(1.15-1.26) 		1.19
(1.14-1.24) 		1.72
(1.64-1.81)
Ctrough,ss 139 (40) 76 (41) 22 (50) 198 (38) 109 (40) 55 (42) 1.42
(1.34-1.51) 		1.43
(1.34-1.53) 		2.55
(2.38-2.74)
Cmax,max 696 (21) 457 (21) 218 (26) 486 (28) 306 (29) 189 (30) 0.7
(0.67-0.73) 		0.67
(0.64-0.7) 		0.87
(0.83-0.91)
Cmax,ss 534 (20) 344 (21) 160 (25) 343 (31) 205 (32) 118 (32) 0.64
(0.62-0.67) 		0.6
(0.57-0.62) 		0.74
(0.71-0.77)

aIV: DL0, 1050 mg (≥80 kg, 1400 mg); DL(-1), 700 mg (≥80 kg, 1050 mg); DL(-2), 350 mg (≥80 kg, 700 mg);
SC: DL0, 1600 mg (≥80 kg, 2240 mg); DL(-1), 1050 mg (≥80 kg, 1600 mg); DL(-2), 700 mg (≥80 kg, 1050 mg).
Note: PK noninferiority criteria to ensure comparable efficacy (lower bound of the GMR 90% CI ≥0.8 for Cavg and Ctrough) and safety (upper bound of the GMR 90% CI ≤1.25 for Cmax) were met for all DLs.

  • Efficacy, safety, and PK results were reported for amivantamab SC plus LAZCLUZE in treatment-naïve patients with EGFR-mutated (Exon19del or Exon 21 L858R) advanced NSCLC (cohort 5).7
  • At the data cutoff of October 24, 20247:
    • Median follow-up was 6.5 months.
    • In total, 67 (87%) patients remained on treatment.

Demographics and baseline disease characteristics7

Characteristic Cohort 5
(n=77)
Median age, years (range) 63 (31–80)
Female, n (%) 52 (68)
Race, n (%)
Asian 48 (62)
White 27 (35)
Othera 2 (3)
ECOG PS 1, n (%) 52 (68)
History of smoking, n (%) 25 (32)
History of brain metastases, n (%) 33 (43)
EGFR mutation,b n (%)
Exon 19del 46 (60)
Exon 21 L858R 31 (40)
Adenocarcinoma histology, n (%) 77 (100)

aIncludes Black or African American and multiple.
bPatients could be included in >1 category.

Primary endpoint

  • The investigator-assessed ORR and the confirmed investigator-assessed ORR with amivantamab SC plus LAZCLUZE was 82% (95% CI, 71-90) and 79% (95% CI, 69-88), respectively.7

Secondary endpoints

  • The ICR-assessed ORR reported with amivantamab SC plus LAZCLUZE was comparable with previous reports of RYBREVANT IV Q2W plus LAZCLUZE.7
    • The ICR-assessed ORR and the confirmed ICR-assessed ORR was 87% (95% CI, 77-94) and 83% (95% CI, 73-91), respectively.
  • The confirmed investigator-assessed and ICR-assessed CBR was 97% (95% CI, 91-100) and 96% (95% CI, 89-99), respectively.7
  • Among the confirmed responders, majority of responses were ongoing (93% [57/61]).7

Investigator-assessed best response, TTR, and DOR7

Parameters Cohort 5
(n=75)
Best response,a n
PR 61
SD 14
Median TTR,b weeks (range) 8.1 (7-16.5)
Median DOR,b months (95% CI) NR

aAmong patients with measurable disease at baseline.
bAmong confirmed responders (n=61).

  • Median PFS and OS were not reached for estimation.7
  • The most common TEAEs were EGFR/MET-related. No new safety signals were identified.7
    • No prophylactic measures for dermatologic AEs were recommended.
  • ARRs (defined per the MedDRA preferred term and referred to as infusion-related reactions in prior IV studies) were reported in 9 (12%) patients.7
    • ARRs (78%; 7/9) were mostly reported in C1 (on or after C1D1 but before the next dose).
    • One patient (1%) reported grade ≥3 ARR.
    • Rate of ARRs was ~5-fold lower compared with previous reports of RYBREVANT IV Q2W plus LAZCLUZE.
  • TRAEs leading to discontinuation of both amivantamab SC and LAZCLUZE were reported in 8% of patients.7

Summary of AEs7

Most common TEAEs (≥20%), n (%) Cohort 5
(n=77)
All grades Grade ≥3
Associated with EGFR inhibition
Paronychia 56 (73) 4 (5)
Rash 45 (58) 9 (12)
Dermatitis acneiform 31 (40) 6 (8)
Stomatitis 29 (38) 3 (4)
Pruritus 26 (34) 1 (1)
Diarrhea 22 (29) 2 (3)
Associated with MET inhibition
Hypoalbuminemia 49 (64) 4 (5)
Peripheral edema 28 (36) 0
Other
Increased ALT 25 (32) 3 (4)
Increased AST 21 (27) 1 (1)
Dry skin 18 (23) 0
  • Majority of patients (87%; 67/77) received prophylactic anticoagulation.7
  • VTEs were reported in 10 (13%) patients.7
    • No grade ≥3 VTEs were reported.
    • No VTEs led to dose reductions, discontinuations, or deaths.
    • Grade ≥3 bleeding rates were reported in 1% of patients.7

VTE and bleeding events based on prophylactic anticoagulation use7

n (%) Any prophylactic
anticoagulation
(n=67) 		No prophylactic
anticoagulation
(n=10) 		Total
(n=77)
Any VTE 7 (10) 3 (30) 10 (13)
Grade ≥3 0 0 0
Grade 5 0 0 0
Any VTE leading to any discontinuation 0 0 0
Grade ≥3 bleeding 1 (1) 0 1 (1)
  • Consistent with historic RYBREVANT IV and SC Q2W data, mean (%CV) amivantamab plasma concentration on C2D1 was 366 (31) µg/mL (n=56).7
  • Cohort 7 is evaluating the efficacy and safety of amivantamab SC plus chemotherapy after first-line RYBREVANT plus LAZCLUZE in patients with EGFR-mutated (Exon19del or Exon 21 L858R) advanced NSCLC.7
  • At a median follow-up of 3.6 months (clinical data cutoff August 6, 2025), 10 patients who had disease progression on RYBREVANT plus LAZCLUZE have received amivantamab SC plus chemotherapy.7

Efficacy

  • The ORR was 50% among the 8 response evaluable patients (patients who had ≥1 disease assessment or discontinued for any reason prior to first disease assessment).7

Best response7

Parameters Cohort 7
(n=8)
Best response,a n
PR 4
SD 2
NE 1

aOne patient discontinued before first disease assessment is not shown.

Safety

  • Early safety profile was consistent with prior report of amivantamab SC plus chemotherapy.7
AE Adverse event GM Geometric mean
ALT Alanine aminotransferase GMR Geometric mean ratio
ARR Administration-related reaction ICR Independent central review
AST Aspartate aminotransferase IgG1 Immunoglobulin G1
AUC Area under the curve INV Investigator
BW Body weight IV Intravenous
C Cycle max Maximum
Cavg Average concentration MedDRA Medical Dictionary for Regulatory Activities
CBR Clinical benefit rate MET Mesenchymal-epithelial transition
CI Confidence interval mTASQ Modified Therapy Administration Satisfaction Questionnaire
Cmax Maximum concentration NE Not estimable
CR Complete response NR Not reached
Ctrough Trough concentration NSCLC Non-small cell lung cancer
CV Coefficient of variation ORR Objective response rate
D Day OS Overall survival
DL Dose level PD Progressive disease
DOR Duration of response PFS Progression-free survival
ECOG PS Eastern Cooperative Oncology Group performance status PK Pharmacokinetics
EGFR Epidermal growth factor receptor PO Orally
EOT End of treatment PR Partial response
Exon19del Exon 19 deletion PRO Patient-reported outcome
Exon20ins Exon 20 insertion Q2W Every 2 weeks
Q3W Every 3 weeks SD Stable disease
Q4W Every 4 weeks SMQ Standardized MedDRA query
QD Once daily ss Steady state
QW Once a week TEAE Treatment-emergent adverse event
RECIST v1.1 Response Evaluation Criteria in Solid
Tumors version 1.1 		TRAE Treatment-related adverse event
rHuPH20 Recombinant human hyaluronidase PH20 TTR Time to response
SC Subcutaneous US United States
SC-CF Subcutaneous coformulation with
recombinant human hyaluronidase PH20 		VTE Venous thromboembolism

A literature search of MEDLINE®, Embase®, BIOSIS Previews®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 17 October 2025.

  1. Moores SL, Chiu ML, Bushey BS, et al. A novel bispecific antibody targeting EGFR and cMet is effective against EGFR inhibitor-resistant lung tumors. Cancer Res. 2016;76(13):3942-3953.
  2. 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.
  3. 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.
  4. Lim SM, Tan JL, Dias JM, et al. Subcutaneous amivantamab and lazertinib as first-line treatment in patients with EGFR-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.
  5. Janssen Research & Development, LLC. A phase 2, open-label, parallel cohort study of subcutaneous amivantamab in multiple regimens in patients with advanced or metastatic solid tumors including EGFR-mutated non-small cell lung cancer. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 October 17]. Available from: https://clinicaltrials.gov/study/NCT05498428 NLM Identifier: NCT05498428.
  6. Lim SM, Tan JL, Wang J, et al. First-line subcutaneous amivantamab plus chemotherapy in EGFR Exon 20 insertion-mutated advanced NSCLC: results from PALOMA-2. Oral Presentation presented at: International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer (WCLC); September 6-9, 2025; Barcelona, Spain.
  7. Scott SC, Dias JM, Liu B, et al. PALOMA-2: subcutaneous amivantamab administered every 4 weeks plus lazertinib in first-line EGFR-mutated advanced NSCLC. Oral Presentation presented at: International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer (WCLC); September 6-9, 2025; Barcelona, Spain.
  8. Nadal E, Neal JW, Signorelli D, et al. Subcutaneous amivantamab plus chemotherapy in EGFR-mutant advanced non-small cell lung cancer after disease progression on osimertinib. Poster presented at: European Society for Medical Oncology (ESMO) Congress; October 17-21, 2025; Berlin, Germany.
  9. Lim SM, Han JY, Zhang J, et al. Subcutaneous after intravenous amivantamab in advanced NSCLC: initial results from PALOMA-2. Poster presented at: European Lung Cancer Congress (ELCC); March 26-29, 2025; Paris, France.
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