J&J Medical Connect
RYBREVANT FASPRO™

(amivantamab and hyaluronidase-lpuj)

J&J Medical Connect

Connect with us

Connect with us

This information is intended for US healthcare professionals to access current scientific information about J&J Innovative Medicine products. It is prepared by Medical Information and is not intended for promotional purposes, nor to provide medical advice.

RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj)

Medical Information

Safety Information for RYBREVANT FASPRO - Venous Thromboembolism

Last Updated: 12/17/2025

SUMMARY

  • RYBREVANT FASPRO (amivantamab and hyaluronidase-lpuj) for subcutaneous (SC) administration is a coformulation of amivantamab with recombinant human hyaluronidase PH20 (rHuPH20).1
  • RYBREVANT (amivantamab-vmjw) is a low fucose, fully human, immunoglobulin G1 (IgG1)-based bispecific antibody with immune cell-directing activity that targets epidermal growth factor receptor (EGFR) mutations and mesenchymal-epithelial transition (MET) mutations and amplifications in non-small cell lung cancer (NSCLC).2
  • LAZCLUZE (lazertinib) is a third-generation EGFR tyrosine kinase inhibitor.3
  • PALOMA-3 (NCT05388669) is a phase 3, open-label, international, randomized study evaluating the pharmacokinetics (PK), efficacy, and safety of RYBREVANT FASPRO plus LAZCLUZE (n=206) vs RYBREVANT plus LAZCLUZE (n=212) in patients with EGFR-mutated (Exon 19 deletion [Exon19del] or Exon 21 L858R) locally advanced or metastatic NSCLC who experienced disease progression on or after osimertinib and platinum-based chemotherapy (N=418).1,4
    • The venous thromboembolism (VTE) rate was 9% (19/206) in the RYBREVANT FASPRO plus LAZCLUZE group and 14% (30/210) in the RYBREVANT plus LAZCLUZE group.1
  • PALOMA-2 (NCT05498428) is an ongoing, phase 2, open-label, international, parallel-cohort study evaluating the efficacy and safety of RYBREVANT FASPRO with chemotherapy and/or LAZCLUZE combination therapy in patients with EGFR-mutated advanced NSCLC (N=520).5,6
    • VTE was reported in 13% (16/125) of all patients, with 18% (12/68) in cohort 1 and 7% (4/57) in cohort 6.5
    • VTE was reported in 13% (10/77) of patients in cohort 5.7 
  • Please refer to RYBREVANT FASPRO, RYBREVANT, and LAZCLUZE product labeling for complete safety information, including dose modification guidelines for adverse reactions.
  • Please refer to national oncology supportive care guidelines for additional information.

PRODUCT LABELING

CLINICAL DATA

PALOMA-3 Study

Study Design/Methods

  • Phase 3, randomized, open-label, international study designed to assess the PK, efficacy, and safety of RYBREVANT FASPRO plus LAZCLUZE (n=206) vs RYBREVANT plus LAZCLUZE (n=212) in patients with EGFR-mutated (Exon19del or Exon 21 L858R) locally advanced or metastatic NSCLC who experienced disease progression on or after osimertinib and platinum-based chemotherapy (N=418).1,4
    • RYBREVANT FASPRO 1600 mg SC (2240 mg if body weight [BW] ≥80 kg) was administered once weekly (QW) for the first 4 weeks and then once every 2 weeks (Q2W) thereafter.
    • RYBREVANT 1050 mg intravenous (1400 mg if BW ≥80 kg) was administered QW for the first 4 weeks and Q2W thereafter.
    • LAZCLUZE 240 mg orally (PO) was administered once daily.
    • Prophylactic anticoagulation was recommended for the first 4 months of treatment.

Results

  • At a median follow-up of 7 months (range, 0.1-14.4), the median duration of treatment was 4.7 months (range, 0.1-13.2) for RYBREVANT FASPRO plus LAZCLUZE and 4.1 months (range, 0-13.2) for RYBREVANT plus LAZCLUZE.1
  • The incidence of VTE was 9% in the RYBREVANT FASPRO plus LAZCLUZE group and 14% in the RYBREVANT plus LAZCLUZE group, with pulmonary embolism and deep vein thrombosis being the most common.1 The incidence of VTE is summarized in Table: PALOMA-3: Incidence of VTE.
    • Among all VTE cases, most occurred in the first 4 months (RYBREVANT FASPRO plus LAZCLUZE vs RYBREVANT plus LAZCLUZE, 74% vs 67%).

PALOMA-3: Incidence of VTE1
n (%)
RYBREVANT FASPRO + LAZCLUZE
(n=206)
RYBREVANT + LAZCLUZE
(n=210)
Any VTEa
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)
Abbreviation: VTE, venous thromboembolism.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.

PALOMA-3: VTE and Bleeding Events Based on Prophylactic Anticoagulation Use1
Event, n (%)
RYBREVANT FASPRO + LAZCLUZE
(n=206)
RYBREVANT + LAZCLUZE
(n=210)
Any Prophylactic Anticoagulation (n=164)
No Prophylactic Anticoagulation (n=42)
Any Prophylactic Anticoagulation (n=171)
No Prophylactic Anticoagulation (n=39)
Any VTEa
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 3-4b
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
Abbreviations: C, cycle; D, day; 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.
  • Overall, 80% and 81% of patients in the RYBREVANT FASPRO plus LAZCLUZE and RYBREVANT plus LAZCLUZE groups, respectively, received prophylactic anticoagulation,1 which is summarized in Table: PALOMA-3: Concomitant Anticoagulants.

PALOMA-3: Concomitant Anticoagulants1
Anticoagulant Use, n (%)
RYBREVANT FASPRO + LAZCLUZE
(n=206)
RYBREVANT + LAZCLUZE
(n=210)
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)

PALOMA-2 Study

Study Design/Methods

  • Phase 2, ongoing, parallel-cohort, open-label, international study designed to assess the efficacy and safety of RYBREVANT FASPRO with chemotherapy and/or LAZCLUZE in patients with EGFR-mutated advanced NSCLC.5,6
    • Cohorts 1 and 6: RYBREVANT FASPRO 1600 mg SC (2240 mg if BW ≥80 kg) was administered QW for the first 4 weeks and then Q2W thereafter. LAZCLUZE 240 mg PO was administered once daily.5
      • Prophylactic anticoagulation was recommended in cohort 1 and mandatory in cohort 6 for the first 4 months.
    • Cohort 5: RYBREVANT FASPRO 1600 mg SC (2240 mg if BW ≥80 kg) was administered QW for the first 4 weeks, and then 3520 mg (4640 mg if BW ≥80 kg) Q4W thereafter (28-day cycles). LAZCLUZE 240 mg PO was administered once daily.7
      • Prophylactic anticoagulation was recommended for the first 4 months of treatment.

Results

Cohorts 1 and 6
  • VTE was reported in 13% (16/125) of all patients, with 18% (12/68) in cohort 1 and 7% (4/57) in cohort 6.5
    • Most VTEs were grade 1-2 in severity; no grade 5 events were reported.
    • No VTEs led to dose reduction.
  • Of the 12 patients in the prophylactic anticoagulation group who reported VTE, 11 (92%) developed VTE after discontinuing prophylactic anticoagulation,5 as summarized in Table: PALOMA-2: VTE and Bleeding Events Based on Prophylactic Anticoagulation Use in Cohorts 1 and 6.
    • Median onset time of VTE after discontinuing prophylactic anticoagulation was 70 days (range, 2-185).

PALOMA-2: VTE and Bleeding Events Based on Prophylactic Anticoagulation Use in Cohorts 1 and 65
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)
Abbreviations: AE, adverse event; D, day; PO, orally; SMQ, standardized MedRA Query; VTE, venous thromboembolismaVTE 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.
Cohort 5

PALOMA-2: VTE and Bleeding Events Based on Prophylactic Anticoagulation Use in Cohort 57
n (%)
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)
Abbreviations: VTE, venous thromboembolism

Literature Search

A literature search of MEDLINE®, Embase®, BIOSIS Previews®, and DerwentDrug File (and/or other resources, including internal/external databases) was conducted on 10 December 2025. The information included in this response is limited to relevant data from the PALOMA-3 and PALOMA-2 studies.

 

References

Show
1 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.  
2 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.  
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 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 2025 December 10]. Available from: https://clinicaltrials.gov/study/NCT05388669 NLM Identifier: NCT05388669.  
5 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.  
6 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 December 10]. Available from: https://clinicaltrials.gov/study/NCT05498428 NLM Identifier: NCT05498428.  
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.