amivantamab SC

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 an investigational coformulation with rHuPH20.²
LAZCLUZE (lazertinib) is a third-generation EGFR tyrosine kinase inhibitor.³

PALOMA-3 Study

PALOMA-3 (NCT05388669) is an ongoing, phase 3, open-label, international, randomized study evaluatingthe PK, efficacy, and safety of amivantamab SC plus lazertinib (n=206) vs RYBREVANT IV plus lazertinib (n=212) in patients with EGFR-mutated (Exon19del or Exon 21 L858R) locally advanced or metastatic NSCLC with disease progression on or after osimertinib and platinum-based chemotherapy (N=418). The noninferior coprimary PK endpoints were C_trough and AUC_D1-D15.^2,4 The key secondary endpoints were ORR and PFS. OS was a predefined exploratory endpoint.²
- The GMRs for C_trough at predose (C2D1), C_trough at steady state (C4D1), and C2 AUC_D1-D15 for amivantamab SC and IV administration were 1.15 (90% CI, 1.04-1.26), 1.43 (90% CI, 1.27-1.61), and 1.03 (90% CI,0.98-1.09), respectively.²
- ORR was 30% in the amivantamab SC plus lazertinib group and 33% in the RYBREVANT IV plus lazertinib group, and the median PFS was 6.1 and 4.3 months, respectively. OS was longer in the amivantamab SC plus lazertinib vs RYBREVANT IV plus lazertinib group (HR for death, 0.62; 95% CI, 0.42-0.92; nominal P=0.02).²
- Grade ≥3 AEs were reported in 52% of patients in the amivantamab SC plus lazertinib group and 56% ofpatients in the RYBREVANT IV plus lazertinib group.²
- All-grade IRRs were reported by 13% of patients in the amivantamab SC plus lazertinib group and 66% of patients in the RYBREVANT IV plus lazertinib group. The VTE rate was 9% in the amivantamab SC plus lazertinib group and 14% in the RYBREVANT IV plus lazertinib group.²
- Median administration time was reduced to 4.8 minutes with SC administration from 5 hours (first infusion) with IV administration.²
- Healthcare resource utilization parameters were lower with amivantamab SC vs RYBREVANT IV on C1D1 and C3D1.⁵
  - Patient time in chair was lower with amivantamab SC vs RYBREVANT IV on C1D1 (0.4 vs 6.5 hours) and C3D1 (0.6 vs 3.4 hours).
  - Active healthcare provider time was lower with amivantamab SC vs RYBREVANT IV on C1D1 (5.6 vs 7.6 hours) and C3D1 (2.3 vs 4.4 hours).
  - Patient time in treatment room was lower with amivantamab SC vs RYBREVANT IV on C1D1 (4.7 vs 7.0 hours) and C3D1 (1.5 vs 3.9 hours).
- Patients receiving amivantamab SC reported minimal moderate to very severe injection-site symptoms (pain [C1D1, 14%; C3D1, 16%], swelling [C1D1, 5%; C3D1, 6%], and redness [C1D1, 5%; C3D1, 6%]).⁵
- Patients receiving amivantamab SC were satisfied (C1D1, 86%; C3D1, 90%), were likely to prefer it over IV (C1D1, 77%; C3D1, 81%), and indicated that they would recommend it to other patients (C1D1,78%; C3D1, 81%).⁵

Note: AE, adverse event; AUC_D1-D15, area under the concentration-time curve from D1 to D15; C, cycle; CI, confidence interval; C_trough, trough concentrations; D, day; EGFR, epidermal growth factor receptor; Exon19del, Exon 19 deletion; GMR, geometric mean ratio; HR, hazard ratio; IgG1, immunoglobulin G1; IRR, infusion-related reaction; IV, intravenous; MET, mesenchymal-epithelial transition; NSCLC, non-small cell lung cancer; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PK, pharmacokinetics; SC, subcutaneous; VTE, venous thromboembolism.

Overview^2,4

PALOMA-3 (NCT05388669) is an ongoing phase 3, open-label, international, randomized study designed to assess the PK, efficacy, and safety of amivantamab SC plus lazertinib vs RYBREVANT IV plus lazertinib in patients with EGFR-mutated (Exon19del or Exon 21 L858R) locally advanced or metastatic NSCLC with disease progression on or after osimertinib and platinum-based chemotherapy

Eligibility Criteria^2,4

Inclusion criteria:

Age ≥18 years
Locally advanced or metastatic NSCLC
Disease progression on or after osimertinib and platinum-based chemotherapy (irrespective of order)
EGFR Exon19del or Exon 21 L858R
≥1 measurable lesion per RECIST v1.1
ECOG PS 0-1

Exclusion criteria:

Symptomatic or progressive brain metastasis
Untreated leptomeningeal disease
Uncontrolled pain
Radiation in the past 7 days
History of ILD

Study Design^2,4

PK²

PK Endpoint^a	Amivantamab SC (n=206)	RYBREVANT IV (n=212)	GMR (90% CI)
Mean C_trough, μg/mL (%CV)
C2D1 (predose)	365 (33)	314 (32)	1.15 (1.04-1.26)
C4D1 (steady state)	224 (39)	162 (42)	1.43 (1.27-1.61)
Mean C2 AUC_D1-D15, μg·h/mL (% CV)	142,236 (31)	135,552 (24)	1.03 (0.98-1.09)
^aThe PK population for evaluating the coprimary PK endpoints included all patients who received all doses without dose modifications prior to the respective endpoint and who provided the PK samples necessary to derive each parameter.

Efficacy Results²

Endpoints	Amivantamab SC (n=206)	RYBREVANT IV (n=212)
ORR, % (95% CI)	30 (24-37)	33 (26-39)
Median OS, months (95% CI)	12.9 (12.9-NE)	NE (10.2-NE)
Median PFS, months (95% CI)	6.1 (4.3-8.1)	4.3 (4.1-5.7)

OS was longer in the amivantamab SC plus lazertinib vs RYBREVANT IV plus lazertinib group (HR for death, 0.62; 95% CI, 0.42-0.92; nominal P=0.02).

Safety Results²

Grade ≥3 AEs were reported in 52% of patients in the amivantamab SC plus lazertinib group and 56% of patients in the RYBREVANT IV plus lazertinib group.
All-grade IRRs were reported by 13% of patients in the amivantamab SC plus lazertinib group and 66% of patients in the RYBREVANT IV plus lazertinib group.
The VTE rate was 9% in the amivantamab SC plus lazertinib group and 14% in the RYBREVANT IV plus lazertinib group.

Note: % CV, % coefficient of variation; AE, adverse event; AUC_D1-D15, area under the concentration-time curve from D1 to D15; C, cycle; CI, confidence interval; C_trough, trough concentrations; D, day; ECOG PS, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor; Exon19del, Exon 19 deletion; GMR, geometric mean ratio; HR, hazard ratio; ILD, interstitial lung disease; IRR, infusion-related reaction; IV, intravenous; NE, not estimable; NSCLC, non-small cell lung cancer; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PK, pharmacokinetics; PO, orally; Q2W, every 2 weeks; QD, once daily; QW, once a week; RECIST v1.1, Response Evaluation Criteria in Solid Tumors version 1.1; SC, subcutaneous; VTE, venous thromboembolism.

PALOMA-3 (NCT05388669) is an ongoing phase 3, open-label, international, randomized study designed to assess the PK, efficacy, and safety of amivantamab SC plus lazertinib vs RYBREVANT IV plus lazertinib in patients with EGFR-mutated (Exon19del or Exon 21 L858R) locally advanced or metastatic NSCLC with disease progression on or after osimertinib and platinum-based chemotherapy.^2,4

PALOMA-3 Study Design^2,4

PALOMA-3 (ClinicalTrials.gov Identifier: NCT05388669) enrollment period: August 2022 to October 2023; data cutoff date: January 3, 2024.²
^aAll patients were required to undergo brain imaging at baseline; subsequent imaging was performed Q6W in patients with baseline brain metastases or as clinically indicated.
^bFor calculating the primary and key secondary outcomes, a sample size of 400 patients was estimated to provide >95% power with a 1-sided alpha of 0.05 allocated to each of the coprimary endpoints and 80% power with a 1-sided alpha of 0.025 allocated to ORR. A hierarchical testing approach at a 2-sided alpha of 0.05 was used for the coprimary endpoints (noninferiority), followed by ORR (noninferiority) and PFS (superiority), which used a combined 2-sided alpha of 0.05.
^CTwo definitions of the same endpoint were used per regional health authority guidance.
^dSC amivantamab was co-formulated with rHuPH20 at a concentration of 160 mg/mL.
^eC1 for IV: D1, D2 (D2 applies to IV split dose only [350 mg on D1 and the remainder on D2]), D8, D15, and D22; C1 for SC: D1, D8, D15, and D22; after C1 for all: D1 and D15 (28-day cycles).
^f2240 mg if BW ≥80 kg.
^g1400 mg if BW ≥80 kg.

A total of 418 patients were randomized to receive amivantamab SC plus lazertinib (n=206) or RYBREVANT IV plus lazertinib (n=212).²

Patient Disposition²

Disposition, n (%)	Randomized (N=418)
Disposition, n (%)	Amivantamab SC + Lazertinib (n=206)	RYBREVANT IV + Lazertinib (n=212)
Received treatment	206 (100)	210 (99)
Treatment ongoing^a	92 (45)	96 (46)
Discontinued treatment	114 (55)	114 (54)
PD	85 (41)	83 (40)
AE	23 (11)	25 (12)
Withdrawal by patient	4 (2)	5 (2)
Physician decision	2 (1)	1 (0.5)
^aData cutoff date: January 3, 2024.

Demographics and Baseline Disease Characteristics²

Characteristic
Characteristic	Amivantamab SC + Lazertinib (n=206)	RYBREVANT IV + Lazertinib (n=212)
Median age, years (range)	61 (35-82)	62 (29-81)
<65 years, n (%)	133 (65)	120 (57)
≥65 to <75 years, n (%)	55 (27)	70 (33)
≥75 years, n (%)	18 (9)	22 (10)
Male/female, n (%)	68 (33)/138 (67)	71 (33)/141 (67)
Median BW, kg (range)	61.8 (35-130)	60.1 (33-150)
<80 kg/≥80 kg, n (%)	184 (89)/22 (11)	184 (87)/28 (13)
Race, n (%)
Asian	126 (61)	129 (61)
White	78 (38)	77 (36)
Black or African American	1 (0.5)	3 (1)
Multiple	0	1 (0.5)
Not reported	1 (0.5)	2 (0.9)
Region, n (%)^a
North America	19 (9)	30 (14)
South America	11 (5)	17 (8)
Europe	38 (18)	40 (19)
Asia	126 (61)	120 (57)
Oceania	12 (6)	5 (2)
^aRussia was counted as part of Europe; Turkey and Israel were counted as part of Asia.

Coprimary PK Endpoints (Noninferiority)

The GMRs for C_trough and C2 AUC_D1-D15 were estimated for amivantamab SC and IV administration.²

GMRs for SC vs IV Administration²

PK Endpoint^a	Amivantamab SC (n=206)	Amivantamab IV (n=212)	GMR (90% CI)
Mean C_trough, μg/mL (%CV)
C2D1 (predose)	365 (33)	314 (32)	1.15 (1.04-1.26)
C4D1 (steady state)	224 (39)	162 (42)	1.43 (1.27-1.61)
Mean C2 AUC_D1-D15, μg·h/mL (% CV)	142,236 (31)	135,552 (24)	1.03 (0.98-1.09)
^aThe PK population for evaluating the coprimary PK endpoints included all patients who received all doses without dose modifications prior to the respective endpoint and who provided the PK samples necessary to derive each parameter.

Treatment-emergent anti-amivantamab antibodies were reported in 1 (0.6%) patient in the amivantamab SC group and none in the RYBREVANT IV group.²
Treatment-emergent anti-rHuPH20 antibodies were reported in 15 (8%) patients in the amivantamab SC group.²

The ORR, best responses, and DCR were evaluated for the amivantamab SC plus lazertinib and RYBREVANT IV plus lazertinib groups.²

Key Efficacy Endpoints²

Endpoint^a	Amivantamab SC + Lazertinib (n=206)	RYBREVANT IV + Lazertinib (n=212)
Endpoint^a	ORR, % (95% CI)^b
All responders	30 (24-37)	33 (26-39)
RR (95% CI)	0.92 (0.70-1.23)
Confirmed responders	27 (21-33)	27 (21-33)
Best response, n (%)
CR^c	1 (0.5)	1 (0.5)
PR^c	61 (30)	68 (32)
SD	93 (45)	81 (38)
PD	37 (18)	42 (20)
NE	14 (7)	20 (9)
DCR, % (95% CI)^d	75 (69-81)	71 (64-77)
Median TTR, months (range)	1.5 (1.2-6.9)	1.5 (1.2-9.9)
^aThe efficacy population included all the patients who had undergone randomization. ^bThe objective response (CR or PR as best response) was assessed by the investigator using RECIST v1.1 and analyzed using logistic regression. The ORR in the amivantamab SC plus lazertinib group met the noninferiority criterion (lower 95% CI bound equals 70%) by retaining ≥60% of the ORR in the IV group. ^cAmong all responders. ^dNot protocol specified; all responders were included.

Median DOR among confirmed responders was 11.2 months (95% CI, 6.1-NE) in the amivantamab SC plus lazertinib group and 8.3 months (95% CI, 5.4-NE) in the RYBREVANT IV plus lazertinib group.²
- In total, 29% of patients in the amivantamab SC plus lazertinib group and 14% in the RYBREVANT IV plus lazertinib group had a DOR of ≥6 months.
Median PFS was 6.1 months (95% CI, 4.3-8.1) in the amivantamab SC plus lazertinib group and 4.3 months (95% CI, 4.1-5.7) in the RYBREVANT IV plus lazertinib group (HR, 0.84; 95% CI, 0.64-1.10; P=0.20).²
- The PFS rates in the amivantamab SC plus lazertinib and RYBREVANT IV plus lazertinib groups, respectively, were 50% (95% CI, 43-58) and 42% (95% CI, 35-50) at 6 months and 37% (95% CI, 28-46) and 20% (95% CI, 8-35) at 12 months.

ORR across predefined subgroups was evaluated for the amivantamab SC plus lazertinib and RYBREVANT IV plus lazertinib groups.²

ORR Across Predefined Subgroups²

Subgroup	RR (95% CI)	No. of Responders/No. of Patients (%)
Subgroup	RR (95% CI)	Amivantamab SC + Lazertinib	RYBREVANT IV + Lazertinib
All randomized patients	0.92 (0.7-1.23)	62/206 (30)	69/212 (33)
Age
<65 years	0.95 (0.63-1.43)	35/133 (26)	38/120 (32)
≥65 years	0.9 (0.56-1.44)	27/73 (37)	31/92 (34)
<75 years	0.93 (0.69-1.26)	57/188 (30)	63/190 (33)
≥75 years	0.86 (0.28-2.61)	5/18 (28)	6/22 (27)
Sex
Female	0.87 (0.61-1.24)	43/138 (31)	51/141 (36)
Male	1.09 (0.59-1.99)	19/68 (28)	18/71 (25)
Race
Asian	0.81 (0.54-1.19)	36/126 (29)	46/129 (36)
Non-Asian	1.16 (0.69-1.96)	26/79 (33)	23/81 (28)
BW
<80 kg	0.89 (0.65-1.22)	53/184 (29)	61/184 (33)
≥80 kg	1.16 (0.47-2.86)	9/22 (41)	8/28 (29)
ECOG PS
0	0.98 (0.54-1.76)	19/58 (33)	20/61 (33)
1	0.9 (0.63-1.29)	43/148 (29)	49/151 (32)
History of smoking
Yes	1.18 (0.68-2.08)	23/65 (35)	20/67 (30)
No	0.82 (0.56-1.19)	39/141 (28)	49/145 (34)
EGFR mutation
Exon19del	0.75 (0.51-1.11)	35/135 (26)	48/138 (35)
Exon 21 L858R	1.32 (0.78-2.25)	27/71 (38)	21/74 (28)
History of brain metastases
Yes	1.07 (0.63-1.83)	24/71 (34)	23/73 (32)
No	0.85 (0.58-1.25)	38/135 (28)	46/139 (33)
Last therapy
Osimertinib	0.81 (0.48-1.36)	22/91 (24)	28/96 (29)
Chemotherapy	1 (0.68-1.45)	40/115 (35)	41/116 (35)

Median OS was 12.9 months (95% CI, 12.9-NE) in the amivantamab SC plus lazertinib group and NE (95% CI, 10.2-NE) in the RYBREVANT IV plus lazertinib group (HR, 0.62; 95% CI, 0.42-0.92; nominal P=0.02; endpoint was exploratory and not part of hierarchical hypothesis testing).²
- The OS rates in the amivantamab SC plus lazertinib and RYBREVANT IV plus lazertinib groups, respectively, were 85% (95% CI, 79-89) and 75% (95% CI, 68-80) at 6 months and 65% (95% CI, 52-74) and 51% (95% CI, 37-64) at 12 months.

At a median follow-up of 7 months (range, 0.1-14.4), the median treatment duration was 4.7 months (range, 0.1-13.2) in the amivantamab SC plus lazertinib group and 4.1 months (range, 0-13.2) in the RYBREVANT IV plus lazertinib group. The incidence of AEs reported across both groups was consistent with previous reports of RYBREVANT IV plus lazertinib.²

Safety Summary²

AE, n (%)	Amivantamab SC + Lazertinib (n=206)	RYBREVANT IV + Lazertinib (n=210)
AE, n (%)	Any AEs	204 (99)	209 (99)
Grade ≥3 AEs	107 (52)	118 (56)
Serious AEs	59 (29)	64 (30)
AEs leading to death	7 (3)	10 (5)
Any AE leading to treatment
Interruptions of any agent^a	127 (62)	127 (60)
Reductions of any agent	63 (31)	52 (25)
Discontinuations of any agent	26 (13)	29 (14)
^aExcluding infusion/administration-related reactions. Note: The safety population included all the patients who had undergone randomization and received ≥1 dose of any trial treatment.

The median time to treatment discontinuation was 6.7 months (95% CI, 4.9-8.4) in the amivantamab SC plus lazertinib group and 5.6 months (95% CI, 4.2-6.9) in the RYBREVANT IV plus lazertinib group (HR, 0.86; 95% CI, 0.66-1.12).²
Treatment-related AEs leading to discontinuation were reported in 9% of patients in the amivantamab SC plus lazertinib group and 12% in the RYBREVANT IV plus lazertinib group.²
The dose reduction rate was 31% in the amivantamab SC plus lazertinib group and 25% in the RYBREVANT IV plus lazertinib group; the corresponding rates due to grade ≥3 AEs were 3% and 4%, respectively.²
Rash was the leading cause of dose reductions in the amivantamab SC plus lazertinib and RYBREVANT IV plus lazertinib groups (8% vs 4%), with the similar incidence of all-grade rash (46% vs 43%) and grade ≥3 rash (3% vs 4%) in both groups.²
The median duration of rash was 31 days in the amivantamab SC plus lazertinib group and 44 days in the RYBREVANT IV plus lazertinib group.²
The most common grade ≥3 AE was dermatitis acneiform, reported in 9% of patients in the amivantamab SC plus lazertinib group and 6% of patients in the RYBREVANT IV plus lazertinib group.²

AE of Special Interest: IRR-Related Events

All-grade IRRs were reported in 13% of patients in the amivantamab SC plus lazertinib group and 66% of patients in the RYBREVANT IV plus lazertinib group.²
- No grade 4-5 events were reported.
- Most IRRs were reported during C1.

Summary of IRRs²

Parameters	Amivantamab SC + Lazertinib (n=206)	RYBREVANT IV + Lazertinib (n=210)
Parameters	All-grade IRRs, %	13	66
Grade ≥3 IRRs, n (%)	1 (0.5)	8 (4)
IRRs leading to discontinuations, n (%)	0	4 (2)

The incidence rates of infusion-related AEs ranged between 0% and 6% in the amivantamab SC plus lazertinib group and 2% and 20% in the RYBREVANT IV plus lazertinib group.²

AE of Special Interest: VTE²

The incidence of VTE was 9% in the amivantamab SC plus lazertinib group and 14% in the RYBREVANT IV plus lazertinib group, with pulmonary embolism and deep vein thrombosis being the most common.²
- Among all VTE cases, most occurred in the first 4 months (amivantamab SC plus lazertinib vs RYBREVANT IV plus lazertinib, 74% vs 67%).
VTE was reported in 10% (32/335) of patients receiving prophylactic anticoagulation and 21% (17/81) of patients not receiving prophylactic anticoagulation.²

AE of Special Interest: VTE²

n (%)	Amivantamab SC + Lazertinib (n=206)	RYBREVANT IV + Lazertinib (n=210)
n (%)	Any VTE^a	19 (9)	30 (14)
Grade 1	1 (0.5)	7 (3)
Grade 2	16 (8)	16 (8)
Grade 3	2 (1)	6 (3)
Grade 4	0	1 (0.5)
Grade 5	0	0
Any VTE leading to death	0	0
Any VTE leading to discontinuation of any agent	0	2 (1)
^aVTE events include pulmonary embolism, deep vein thrombosis, embolism venous, venous thrombosis limb, embolism, thrombosis, subclavian vein thrombosis, superficial vein thrombosis, pulmonary infarction, and venous thrombosis. Note: The safety population included all the patients who had undergone randomization and received ≥1 dose of any trial treatment.

Overall, 80% and 81% of patients in the amivantamab SC plus lazertinib and RYBREVANT IV plus lazertinib groups, respectively, received prophylactic anticoagulation.²

Concomitant Anticoagulants²

Anticoagulant Use, n (%)	Amivantamab SC + Lazertinib (n=206)	RYBREVANT IV + Lazertinib (n=210)
Anticoagulant Use, n (%)	Patients with ≥1 concomitant anticoagulant	164 (80)	171 (81)
Antithrombotic agents
Direct factor Xa inhibitors	132 (64)	143 (68)
Rivaroxaban	89 (43)	76 (36)
Apixaban	38 (18)	54 (26)
Edoxaban	7 (3)	17 (8)
Heparin group	48 (23)	45 (21)
Enoxaparin	39 (19)	35 (17)
Heparin	4 (2)	2 (1)
Tinzaparin	3 (2)	2 (1)
Low molecular weight heparin	3 (2)	1 (0.5)
Bemiparin	2 (1)	3 (1)
Nadroparin	1 (0.5)	2 (1)
Dalteparin	0	1 (0.5)
Other antithrombotic agents	1 (0.5)	3 (1)
Fondaparinux	1 (0.5)	3 (1)
Direct thrombin inhibitors	0	1 (0.5)
Dabigatran	0	1 (0.5)
Vitamin K antagonists	0	1 (0.5)
Warfarin	0	1 (0.5)

At C1D1, median administration time was reduced to 4.8 minutes (range, 0-18) with SC administration from 5 hours (range, 0.2-9.9) for the first infusion with IV administration.²
The patient-reported treatment satisfaction was evaluated for amivantamab SC vs RYBREVANT IV administration at C1D1, C3D1, and EOT.^2,5

Patient-Reported Treatment Satisfaction^2,5

Response^a	Amivantamab SC^b	RYBREVANT IV^b	Nominal P-Value
C1D1^c	n=193	n=195
Unrestricted^d, %	66	29	<0.001
Unbothered^e, %	69	30
Convenient or very convenient, %	85	52
C3D1	n=146	n=125
Unrestricted^d, %	60	42	0.004
Unbothered^e, %	71	45	<0.001
EOT^f	n=61	n=55
Convenient or very convenient, %	85	35	<0.001
^aResponse categories on the mTASQ convenience question included “very convenient,” “convenient,” “neither convenient nor inconvenient,” “inconvenient,” and “very Inconvenient.” The mTASQ is an 11-item questionnaire measuring the impact of each mode of treatment administration on 5 domains: physical impact, psychological impact, impact on activities of daily living, convenience, and satisfaction. ^bIncludes patients whose answer was “very convenient” or “convenient.” ^cC1D2 for patients who received RYBREVANT IV due to split dosing. ^dQuestion asked in the questionnaire was “When receiving the injection/infusion, do you feel restricted?” ^eQuestion asked in the questionnaire was “How bothered are you by the amount of time it takes to have the infusion/injection?” ^fData could have been collected after the final treatment dose.

Patients receiving amivantamab SC reported minimal moderate to very severe injection-site symptoms (pain [C1D1, 14%; C3D1, 16%], swelling [C1D1, 5%; C3D1, 6%], and redness [C1D1, 5%; C3D1, 6%]).²
Patients receiving amivantamab SC were satisfied (C1D1, 86%; C3D1, 90%), were likely to prefer it over IV (C1D1, 77%; C3D1, 81%) and indicated that they would recommend it to other patients (C1D1, 78%; C3D1, 81%).²

AE	Adverse event	mTASQ	modified Therapy Administration Satisfaction Questionnaire
ALT	Alanine aminotransferase	NE	Not estimable
AST	Aspartate aminotransferase	NSCLC	Non-small cell lung cancer
AUC_D1-D15	Area under the concentration-time curve from C2 D1 to D15	ORR	Objective response rate
BW	Body weight	OS	Overall survival
C	Cycle	PD	Progressive disease
CI	Confidence interval	PFS	Progression-free survival
CR	Complete response	PK	Pharmacokinetics
C_trough	Trough concentrations	PO	Orally
%CV	% Coefficient of variation	PR	Partial response
D	Day	PRO	Patient-reported outcome
DCR	Disease control rate	QD	Once daily
DOR	Duration of response	QW	Once a week
ECOG PS	Eastern Cooperative Oncology Group performance status	Q2W	Every 2 weeks
EGFR	Epidermal growth factor receptor	Q6W	Every 6 weeks
EOT	End of treatment	RECIST v1.1	Response Evaluation Criteria in Solid Tumors version 1.1
Exon19del	Exon 19 deletion	R	Randomization
GMR	Geometric mean ratio	RR	Relative risk
HR	Hazard ratio	rHuPH20	Recombinant human hyaluronidase PH20
IgG1	Immunoglobulin G1	SC	Subcutaneous
ILD	Interstitial lung disease	SD	Stable disease
IRR	Infusion-related reaction	TTR	Time to response
IV	Intravenous	VTE	Venous thromboembolism
MET	Mesenchymal-epithelial transition

A literature search of MEDLINE®, Embase®, BIOSIS Previews®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 03 September 2024.

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.
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.
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.
Janssen Research & Development, LLC. A phase 3, open-label, randomized study of lazertinib with subcutaneous amivantamab compared with intravenous amivantamab in patients with EGFR-mutated advanced or metastatic non-small cell lung cancer after progression on osimertinib and chemotherapy. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2024 September 03]. Available from: https://clinicaltrials.gov/study/NCT05388669 NLM Identifier: NCT05388669
Alexander M, Cheng Y, Lee S-H, et al. Subcutaneous vs intravenous amivantamab: patient satisfaction and resource utilization results from the PALOMA-3 Study. Oral Presentation presented at: International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer (WCLC); September 7-10, 2024; San Diego, CA.

Characteristic	Amivantamab SC + Lazertinib (n=206)	RYBREVANT IV + Lazertinib (n=212)
Median prior lines of therapy (range)	2 (1-5)	2 (1-4)
ECOG PS, n (%)
0	58 (28)	61 (29)
1	148 (72)	151 (71)
EGFR mutation, n (%)
Exon19del	135 (66)	138 (65)
Exon 21 L858R	71 (34)	74 (35)
History of brain metastasis, n (%)
Yes	70 (34)	72 (34)
No	136 (66)	140 (66)
History of smoking, n (%)
Yes	65 (32)	67 (32)
No	141 (68)	145 (68)
Median time from initial diagnosis, months (range)	34.5 (2.8-191.3)	33.7 (6.1-156.9)
Median time from metastatic diagnosis, months (range)	32.7 (0.9-169)	29.7 (0.6-142.6)
Last therapy before randomization, n (%)
Osimertinib	91 (44)	96 (45)
Chemotherapy	115 (56)	116 (55)

ECOG PS, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor;Exon19del, Exon 19 deletion; IV, intravenous; SC, subcutaneous.

Healthcare resource utilization parameters (patient time in chair, active healthcare provider time, and patient time in treatment room) were lower with amivantamab SC vs RYBREVANT IV on C1D1 and C3D1.⁵

Parameters	Amivantamab SC	RYBREVANT IV
C1D1
Patient time in chair^b, h	0.4 (24 min) (n=198)	6.5 (n=198)
Active healthcare provider time^c, h	5.6^e (n=202)	7.6 (n=203)
Patient time in treatment room^d, h	4.7^e (n=201)	7.0 (n=201)
C3D1
Patient time in chair^b, h	0.6 (36 min) (n=163)	3.4 (n=147)
Active healthcare provider time^c, h	2.3 (n=163)	4.4 (n=147)
Patient time in treatment room^d, h	1.5 (n=162)	3.9 (n=148)

Data are presented as median time (hours).
C, cycle; D, day; h, hours; min, minutes; IV, intravenous; SC, subcutaneous.
^aAssessed on C1D1 and C3D1. Immediate feedback at C1D1 and experience-based feedback at C3D1 offers a thorough evaluation of administration impact, patient comfort, ease of use, and potential issues.
^bTime between entry and exit from patient chair.
^cTime collected through stopwatch measurement for prespecified tasks related to drug preparation (IV reconstitution or SC syringe filling and dispensing), treatment administration, and post treatment monitoring. HCPs include nurses, pharmacists, pharmacy technicians/assistant staff and physicians.
^dTime between entry in the treatment room for receiving therapy and exit from the treatment room.
^eTrial required mandatory observation period of 4 hours for SC amivantamab on C1D1.

AEs (≥20% in either group), n (%)	Amivantamab SC + Lazertinib (n=206)		RYBREVANT IV + Lazertinib (n=210)
AEs (≥20% in either group), n (%)	All Grades	Grade ≥3	All Grades	Grade ≥3
Paronychia	111 (54)	8 (4)	108 (51)	3 (1)
Hypoalbuminemia	96 (47)	9 (4)	77 (37)	8 (4)
Rash	95 (46)	8 (4)	91 (43)	8 (4)
Dermatitis acneiform	64 (31)	18 (9)	69 (33)	12 (6)
Nausea	60 (29)	1 (0.5)	52 (25)	3 (1)
Stomatitis	57 (28)	1 (0.5)	69 (33)	5 (2)
Peripheral edema	52 (25)	6 (3)	58 (28)	1 (0.5)
Increased ALT	46 (22)	6 (3)	56 (27)	8 (4)
Decreased appetite	45 (22)	1 (0.5)	52 (25)	3 (1)
Fatigue	44 (21)	3 (2)	43 (20)	5 (2)
Vomiting	44 (21)	2 (1)	41 (20)	1 (0.5)
Diarrhea	43 (21)	3 (1)	39 (19)	2 (1)
Constipation	42 (20)	0	42 (20)	1 (0.5)
Headache	42 (20)	1 (0.5)	36 (17)	1 (0.5)
Increased AST	42 (20)	2 (1)	45 (21)	3 (1)
IRR	27 (13)	1 (0.5)	138 (66)	8 (4)

AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; IRR, infusion-related reaction; IV, intravenous; SC, subcutaneous.
Note: The safety population included all the patients who had undergone randomization and received ≥1 dose of any trial treatment.

Infusion-Related AE, %	Amivantamab SC + Lazertinib (n=206)	RYBREVANT IV + Lazertinib (n=210)
Infusion-Related AE, %	Chills	6	14
Pyrexia	3	3
Dyspnea	3	20
Nausea	3	20
Vomiting	2	15
Cough	2	8
Hypoxia	2	9
Sinus tachycardia	2	5
Hypotension	1	8
Erythema	1	3
Chest discomfort	0.5	6
Hypertension	0.5	6
Flushing	0	12
Dizziness	0	4
Rash	0	3
Hyperhidrosis	0	2
Increased heart rate	0	2

AE, adverse event; IV, intravenous; SC, subcutaneous.
Note: The safety population included all the patients who had undergone randomization and received ≥1 dose of any trial treatment.

Event, n (%)	Amivantamab SC + Lazertinib (n=206)		RYBREVANT IV + Lazertinib (n=210)
Event, n (%)	Any Prophylactic Anticoagulation (n=164)	No Prophylactic Anticoagulation (n=42)	Any Prophylactic Anticoagulation (n=171)	No Prophylactic Anticoagulation (n=39)
Any VTE^a	12 (7)	7 (17)	20 (12)	10 (26)
Grade 1	0	1 (2)	5 (3)	2 (5)
Grade 2	10 (6)	6 (14)	13 (8)	3 (8)
Grade 3-4	2 (1)	0	2 (1)	5 (13)
Grade 5	0	0	0	0
VTE leading to death	0	0	0	0
VTE leading to discontinuation of any agent	0	0	0	2 (5)
Any bleeding event	44 (27)	5 (12)	48 (28)	5 (13)
Grade 3-4^b	3 (2)	1 (2)	1 (0.6)	0
Grade 5	0	0	0	0
Bleeding event leading to death	0	0	0	0
Bleeding event leading to discontinuation of any agent	1 (0.6)	0	0	0

C, cycle; D, day; IV, intravenous; SC, subcutaneous; VTE, venous thromboembolism.
^aVTE events include pulmonary embolism, deep vein thrombosis, venous embolism, venous thrombosis limb, embolism, thrombosis, subclavian vein thrombosis, superficial vein thrombosis, pulmonary infarction, and venous thrombosis.
^bInclude contusion, gingival bleeding, hemoptysis, hematemesis, and nail bed bleeding.
Note: The safety population included all the patients who had undergone randomization and received ≥1 dose of any trial treatment. The group with any prophylactic anticoagulation included patients who had anticoagulation prior to or at C1D1 plus a 3-day window and continued until disease progression, death, withdrawal from the study, occurrence of VTE, or C5D1.

Medical Information

Amivantamab SC, RYBREVANT, LAZCLUZE - PALOMA-3 Study

PALOMA-3 Study

Overview^2,4

Eligibility Criteria^2,4

Study Design^2,4

PK²

Efficacy Results²

Safety Results²

PALOMA-3 Study Design^2,4

Patient Disposition²

Demographics and Baseline Disease Characteristics²

Coprimary PK Endpoints (Noninferiority)

GMRs for SC vs IV Administration²

Key Efficacy Endpoints²

ORR Across Predefined Subgroups²

Safety Summary²

AE of Special Interest: IRR-Related Events

Summary of IRRs²

AE of Special Interest: VTE²

AE of Special Interest: VTE²

Concomitant Anticoagulants²

Patient-Reported Treatment Satisfaction^2,5

Medical inquiries

amivantamab SC

Medical Information

Amivantamab SC, RYBREVANT, LAZCLUZE - PALOMA-3 Study

PALOMA-3 Study

Overview2,4

Eligibility Criteria2,4

Study Design2,4

PK2

Efficacy Results2

Safety Results2

PALOMA-3 Study Design2,4

Patient Disposition2

Demographics and Baseline Disease Characteristics2

Additional Demographics and Baseline Disease Characteristics

Coprimary PK Endpoints (Noninferiority)

GMRs for SC vs IV Administration2

Key Efficacy Endpoints2

ORR Across Predefined Subgroups2

Safety Summary2

Summary of AEs

AE of Special Interest: IRR-Related Events

Summary of IRRs2

Infusion-Related AE

AE of Special Interest: VTE2

AE of Special Interest: VTE2

VTE and Bleeding Events Based on Prophylactic Anticoagulation Use

Concomitant Anticoagulants2

Patient-Reported Treatment Satisfaction2,5

Healthcare Resource Utilization

Medical inquiries

Overview^2,4

Eligibility Criteria^2,4

Study Design^2,4

PK²

Efficacy Results²

Safety Results²

PALOMA-3 Study Design^2,4

Patient Disposition²

Demographics and Baseline Disease Characteristics²

GMRs for SC vs IV Administration²

Key Efficacy Endpoints²

ORR Across Predefined Subgroups²

Safety Summary²

Summary of IRRs²

AE of Special Interest: VTE²

AE of Special Interest: VTE²

Concomitant Anticoagulants²

Patient-Reported Treatment Satisfaction^2,5