J&J Medical Connect
RYBREVANT®

(amivantamab-vmjw)

+ Save link
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® (amivantamab-vmjw)

Medical Information

Use of RYBREVANT in Head & Neck Cancer - OrigAMI-4 Study

Last Updated: 10/20/2025

SUMMARY

  • 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).1
  • Amivantamab for subcutaneous (SC) administration is a coformulation of amivantamab with recombinant human hyaluronidase PH20 (rHuPH20).2
  • OrigAMI-4 (NCT06385080) is an ongoing, phase 1b/2, nonrandomized, open-label, multicenter study evaluating the efficacy and safety of amivantamab SC as monotherapy and in combination with pembrolizumab, paclitaxel, or pembrolizumab plus carboplatin in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), who had disease progression on prior checkpoint inhibitor and platinum-based chemotherapy (cohorts 1, 3, and 4) or were treatment-naïve (cohorts 2 and 5). Enrollment is planned for approximately 247 patients.3-5
    • The investigator-assessed objective response rate (ORR) was 45% (95% confidence interval [CI], 29-62), and median progression-free survival (PFS) was 6.8 months (95% CI, 4.2-9) in the amivantamab SC monotherapy cohort 1, as included in Table: Antitumor Activity in the Amivantamab SC Monotherapy Cohort 1.3 The ORR was 64% (95% CI, 31-89), and median PFS was not estimable (NE) in the amivantamab SC plus paclitaxel combination cohort 3a, as included in Table: Antitumor Activity in the Amivantamab SC plus Paclitaxel Combination Cohort 3a.5  
    • The recommended phase 2 combination dose (RP2CD) identified in the amivantamab SC plus paclitaxel combination cohort 3a was the initial dose level (DL0) combination: amivantamab SC 2400 mg (3360 mg if body weight ≥80 kg) weekly on cycle (C)1 day (D)8 and C1D15 (initial C1D1 dose: 1600 mg or 2240 mg if body weight ≥80 kg), and every 3 weeks (Q3W) on C2D1 and thereafter, plus paclitaxel IV 175 mg/m2 Q3W.5
      • Dose-limiting toxicities (DLTs) were reported in 1 of 7 evaluable patients (grade 3 mucositis and fatigue, both resolved).
    • The safety profile in cohort 1 was consistent with previous reports of amivantamab SC monotherapy, as included in Table: Safety Profile for the Amivantamab SC Monotherapy Cohort 1.3
      • The most common treatment-emergent adverse events (TEAEs) were hypoalbuminemia (31%), fatigue (31%), and stomatitis (23%) and were mostly grade 1-2 in severity.
      • The rate of administration-related reactions (ARRs) was 7%.
      • Treatment-related adverse events (TRAEs) leading to discontinuation (paronychia and elevated alkaline phosphatase) were reported in 2% of patients.
    • The safety profile in cohort 3a was consistent with those of amivantamab SC and paclitaxel, as included in Table: Safety Profile for the Amivantamab SC plus Paclitaxel Combination Cohort 3a.5
      • The most common TEAEs were dermatitis acneiform, paronychia, stomatitis, and fatigue (45% each) and were mostly grade 1-2 in severity.
      • No ARRs related to amivantamab SC were reported.
    • Mean predose amivantamab SC serum concentrations observed were consistent between the amivantamab SC plus paclitaxel combination and amivantamab SC monotherapy cohorts.5

ongoing clinical study

OrigAMI-4 Study

Study Design/Methods

  • Ongoing, phase 1b/2, nonrandomized, open-label, multicenter study designed to assess the efficacy and safety of amivantamab SC as monotherapy and in combination with pembrolizumab, paclitaxel, or pembrolizumab plus carboplatin in patients with R/M HNSCC.3-5
  • The study includes cohorts of patients who had disease progression on prior checkpoint inhibitor (programmed cell death protein 1 [PD-1]/programmed cell death-ligand 1 [PD-L1] inhibitor) and platinum-based chemotherapy (cohorts 1, 3, and 4) or were treatment-naïve (cohorts 2 and 5).3,5
  • The study design is shown in Figure: OrigAMI-4 Study Design.

OrigAMI-4 Study Design3-5

OrigAMI-4 (ClinicalTrials.gov Identifier: NCT06385080).
Abbreviations: AUC, area under the concentration-time curve; BW, body weight; C, cycle; CBR, clinical benefit rate; D, day; DL0, initial dose level; DLT, dose-limiting toxicity; DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor; HNSCC, head and neck squamous cell carcinoma; HPV, human papillomavirus; ILD, interstitial lung disease; ISH, in-situ hybridization; IV, intravenous; ORR, objective response rate; OS, overall survival; PD-1, programmed cell death protein 1; PD-L1, programmed cell death-ligand 1; PFS, progression-free survival; PK, pharmacokinetics; QW, weekly; Q3W, every 3 weeks; RECIST, Response Evaluation Criteria in Solid Tumors; R/M, recurrent/metastatic; RP2D, recommended phase 2 dose; SC, subcutaneous; SET, study evaluation team.
aDefined as having ≥1 nontarget lesion per RECIST version 1.1.
bExcept alopecia, postradiation skin changes (any grade), grade ≤2 peripheral neuropathy, and grade ≤2 hypothyroidism stable on replacement therapy.
c1600 mg (2240 mg if BW ≥80 kg) on C1D1, then 2400 mg (3360 mg if BW ≥80 kg) QW on C1D8 and C1D15, and Q3W on C2D1 and thereafter.
dOn D1 of each 21-day cycle.
eThe RP2CD of amivantamab SC will be determined with SET.
fConfirmed by SET in cohort 3A.
gOn D1 of C1-C6.
hThe maximum required washout is 28 days.

Results: Amivantamab SC Monotherapy Cohort (Cohort 1)

  • Results are reported as of the data cutoff date of July 01, 2025.3
Patient Characteristics
  • Cohort 1 included 86 human papillomavirus (HPV)-unrelated patients with R/M HNSCC who had received ≥1 prior line of therapy and were treated with amivantamab SC monotherapy, with a median follow-up of 3.5 months (range, 0-13.4).3
  • At the data cutoff, 53 of 86 (62%) patients remained on amivantamab SC monotherapy.3
  • Patient characteristics are included in Table: Patient Characteristics in the Amivantamab SC Monotherapy Cohort 1.

Patient Characteristics in the Amivantamab SC Monotherapy Cohort 13
Characteristic
Cohort 1 (n=86)a
Median age, years (range)
63.5 (30-81)
Sex, n (%)
   Male
65 (76)
   Female
21 (24)
Race, n (%)
   Asian
39 (45)
   White
37 (43)
   Otherb
10 (12)
ECOG PS, n (%)
   0
28 (33)
   1
58 (67)
Primary tumor location, n (%)
   Oropharynx
10 (12)
   Oral cavity
42 (49)
   Hypopharynx
13 (15)
   Larynx
21 (24)
Site of recurrence/metastasis,c n (%)
   Bone
14 (17)
   Head and neck
51 (62)
   Liver
5 (6)
   Local lymph node
33 (40)
   Distant lymph node
20 (24)
   Lung
45 (55)
   Skin
1 (1)
   Other
17 (21)
Prior lines of therapy, %
  ≥1
100
   2
43
Abbreviations: ECOG PS, Eastern Cooperative Oncology Group performance status; SC, subcutaneous.
aSafety population (n=86) included patients who received ≥1 dose of amivantamab SC monotherapy.
bOther includes Black or African-American (n=1), not reported (n=6), and unknowns (n=3).
cPatients (n=82) can be counted in >1 category.
Efficacy
  • Efficacy outcomes for amivantamab SC monotherapy in cohort 1 are included in Table: Antitumor Activity in the Amivantamab SC Monotherapy Cohort 1.
  • As of the data cutoff, 38 patients had ≥2 disease assessments (or discontinued before for any reason) and were included in the efficacy analysis.3
    • The first disease assessment was conducted 6 weeks after the first dose, then every 6 weeks (±1 week) for the first year and every 9 weeks (±1 week) thereafter.
  • At a median follow-up of 8.3 months, 16 of 38 (42%) patients remained on amivantamab SC monotherapy.3

Antitumor Activity in the Amivantamab SC Monotherapy Cohort 13
Efficacy Outcome
Cohort 1 (n=38)
Median follow-up, months (range)
8.3 (1.1-13.4)
Investigator-assessed response
   ORR, % (95% CI)
45 (29-62)
   Best response, n (%)
      CR
1 (3)
      PR
16 (42)
      SD
17 (45)
      PD
2 (5)
      Not evaluable
2 (5)
   Time to first response,a weeks
6.4
   CBR,b % (95% CI)
76 (60-89)
   Among confirmed responders, n
17
      Median DOR, months (95% CI)
7.2 (5.3-NE)
      Treatment ongoing, n (%)
11 (65)
      Response duration ≥6 months, %
47
Median PFS, months (95% CI)
6.8 (4.2-9)
Median OS, months (95% CI)
NR (7.7-NE)
Abbreviations: CI, confidence interval; CBR, clinical benefit rate; CR, complete response; DOR, duration of response; NE, not estimable; NR, not reached; ORR, objective response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial response; SC, subcutaneous; SD, stable disease.
aAmong all responders.
bCBR was defined as percentage of confirmed responders or durable SD (at the second disease assessment).
  • Tumor shrinkage of target lesions was observed in 82% of patients.3
  • A 48-year-old female patient diagnosed with oral cavity cancer and metastases in the lung, who was previously treated with surgery, cisplatin/radiation, and nivolumab, exhibited a 65% tumor reduction on computed tomography (CT) scan after 6 weeks of amivantamab SC monotherapy.3
Safety
  • The safety profile in cohort 1 was consistent with previous reports of amivantamab SC monotherapy.3
  • The safety population (n=86) included patients who received ≥1 dose of amivantamab SC monotherapy.3
  • Median treatment duration was 2.7 months (range, 0-11.3).3
  • Most TEAEs were grade 1-2 in severity.3
  • The rate of ARRs was 7%, consistent with previous reports of amivantamab SC.3
    • All ARRs were grade 1-2, with no grade ≥3 events.
  • TRAEs leading to discontinuation (paronychia and elevated alkaline phosphatase) were reported in 2% of patients.3
  • Safety data are included in Table: Safety Profile for the Amivantamab SC Monotherapy Cohort 1.

Safety Profile for the Amivantamab SC Monotherapy Cohort 13
TEAEs (≥10%) by Preferred Term, n (%)
Cohort 1 (n=86)
All Grades
Grade ≥3
Associated with EGFR inhibition
   Stomatitis
20 (23)
1 (1)
   Dermatitis acneiforma
17 (20)
6 (7)
   Rasha
16 (19)
2 (2)
   Paronychiaa
15 (17)
1 (1)
   Diarrhea
13 (15)
0
   Pruritusa
11 (13)
2 (2)
Associated with MET inhibition
   Hypoalbuminemia
27 (31)
2 (2)
   Peripheral edema
12 (14)
1 (1)
Other
   Fatigue
27 (31)
4 (5)
   Anemia
15 (17)
5 (6)
   Hypocalcemia
13 (15)
0
   ALT increased
11 (13)
3 (3)
   Nausea
11 (13)
0
   Weight decreased
11 (13)
1 (1)
   Decreased appetite
10 (12)
0
   Dyspnea
10 (12)
2 (2)
   AST increased
9 (10)
2 (2)
   Lymphopenia
9 (10)
4 (5)
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; EGFR, epidermal growth factor receptor; MET, mesenchymal-epithelial transition; SC, subcutaneous; TEAE, treatment-emergent adverse event.
aProphylactic dermatologic management (COCOON protocol) was not mandatory in the OrigAMI-4 study.

Results: Amivantamab SC plus Paclitaxel Combination Cohort (Cohort 3a)

  • Results are reported as of the data cutoff date of August 6, 2025.5
Patient Characteristics

Patient Characteristics in the Amivantamab SC plus Paclitaxel Combination Cohort 3a5
Characteristic
Cohort 3a (n=11)a
Median age, years (range)
58 (39-69)
Sex, n (%)
   Male
9 (82)
   Female
2 (18)
Race, n (%)
   Asian
7 (64)
   White
3 (27)
   Unknown
1 (9)
Primary tumor location, n (%)
   Hypopharynx
1 (9)
   Larynx
1 (9)
   Oral cavity
8 (73)
   Oropharynx
1 (9)
Abbreviation: SC, subcutaneous.
DLTs
  • DL0 was identified as the RP2CD.5
  • Of the 7 DLT-evaluable patients, 1 experienced DLTs (grade 3 mucositis and fatigue, both resolved).5
Safety

Safety Profile for the Amivantamab SC plus Paclitaxel Combination Cohort 3a5
TEAEs (≥20%) by Preferred Term, n (%)
Cohort 3a (n=11)
All Grades
Grade ≥3
Associated with EGFR inhibition
   Dermatitis acneiform
5 (45)
1 (9)
   Paronychia
5 (45)
0
   Stomatitis
5 (45)
2 (18)
   Rash
4 (36)
0
   Diarrhea
3 (27)
1 (9)
Associated with MET inhibition
   Hypoalbuminemia
3 (27)
0
Other
   Fatigue
5 (45)
1 (9)
   Hypophosphatemia
4 (36)
0
   Neutropenia
3 (27)
 2 (18)
   Pneumonia
3 (27)
2 (18)
   Leukopenia
3 (27)
1 (9)
   Myalgia
3 (27)
1 (9)
   ALT increased
3 (27)
0
   Anemia
3 (27)
0
   Back pain
3 (27)
0
   Constipation
3 (27)
0
   Hypokalemia
3 (27)
0
   Nausea
3 (27)
0
   Pyrexia
3 (27)
0
Abbreviations: ALT, alanine aminotransferase; EGFR, epidermal growth factor receptor; MET, mesenchymal-epithelial transition; SC, subcutaneous; TEAE, treatment-emergent adverse event.
Efficacy

Antitumor Activity in the Amivantamab SC plus Paclitaxel Combination Cohort 3a5
Efficacy Outcome
Cohort 3a (n=11)
ORR, % (95% CI)
64 (31-89)
Best response, n
   CR
1a
   PR
8
   Not evaluable/unknown
2
Median DOR, months
NR
Median time to first response, weeks (range)
6.6 (6.1-14.6)
Tumor shrinkage of target lesions, n
9
Among confirmed responders, n (%)
7 (64)
   Treatment ongoing, n
4
Median PFS, months
NE
Median OS, months
NE
Abbreviations: CI, confidence interval; CR, complete response; DOR, duration of response; NE, not estimable; NR, not reached; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; SC, subcutaneous.
aResponse ongoing.
  • Antitumor activity among responders was observed regardless of baseline biomarker status.5
Pharmacokinetics
  • Mean predose amivantamab SC serum concentrations observed were consistent between the amivantamab SC plus paclitaxel combination (n=11) and amivantamab SC monotherapy (n=71) cohorts, suggesting that amivantamab SC pharmacokinetics exposure was not impacted by paclitaxel.5

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 17 October 2025.

References

Show
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 Harrington KJ, Rosenberg AJ, Yang M-H, et al. Amivantamab in recurrent/metastatic head & neck squamous cell cancer after disease progression on checkpoint inhibition and chemotherapy: results from the phase 1b/2 OrigAMI-4 study. Oral Presentation presented at: European Society for Medical Oncology (ESMO) Congress; October 17-21, 2025; Berlin, Germany.  
4 Janssen Research & Development, LLC. A phase 1b/2, open-label study of amivantamab monotherapy and amivantamab in addition to standard of care therapeutic agents in participants with recurrent/metastatic head and neck squamous cell carcinoma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 October 17]. Available from: https://www.clinicaltrials.gov/study/NCT06385080 NLM Identifier: NCT06385080.  
5 Swiecicki PL, Keam B, Li S-H, et al. Amivantamab plus paclitaxel in recurrent/metastatic head and neck squamous cell cancer after disease progression on checkpoint inhibitor: identification of the recommended combination dose from the phase 1b/2 OrigAMI-4 study. Poster presented at: European Society for Medical Oncology (ESMO) Congress; October 17-21, 2025; Berlin, Germany.