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RYBREVANT FASPRO™

(amivantamab and hyaluronidase-lpuj)

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RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj)

Medical Information

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

Last Updated: 02/23/2026

SUMMARY

  • RYBREVANT FASPRO (amivantamab and hyaluronidase-lpuj) for subcutaneous (SC) administration is a coformulation of amivantamab with recombinant human hyaluronidase PH20 (rHuPH20).1
  • OrigAMI-4 (NCT06385080) is an ongoing, phase 1b/2, nonrandomized, open-label, multiarm, 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) or locally advanced HNSCC, who had disease progression on/after prior checkpoint inhibitor and platinum-based chemotherapy (cohorts 1, 3, and 4) or were treatment-naïve (cohorts 2, 5, and 6). Enrollment is planned for approximately 287 patients.2-6
  • Cohort 13:
    • The investigator-assessed confirmed 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 (n=38), as included in Table: Antitumor Activity in the Amivantamab SC Monotherapy Cohort 1. 
    • The safety profile in cohort 1 (n=86) was consistent with previous reports of amivantamab SC monotherapy, as included in Table: Safety Summary in Cohort 1.
      • Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 47% of patients.
      • The most common 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% (n=6).
      • Treatment-related adverse events (TRAEs) leading to discontinuation of treatment (paronychia [n=1] and elevated alkaline phosphatase [n=1]) were reported in 2% of patients.
  • Cohort 24:
    • The investigator-assessed ORR was 56% (95% CI, 40-72), and median PFS was 7.7 months (95% CI, 5-not estimable [NE]) in the amivantamab SC plus pembrolizumab combination cohort 2 (n=39), as included in Table: Antitumor Activity in the Amivantamab SC plus Pembrolizumab Combination Cohort 2.
    • The safety profile in cohort 2 (n=39) was consistent with those of amivantamab SC and pembrolizumab, with no new safety signals identified, as included in Table: Safety Profile for the Amivantamab SC plus Pembrolizumab Combination Cohort 2.
      • TRAEs leading to discontinuation of treatment pneumonitis [n=2], hepatitis [n=1], and Stevens-Johnson syndrome [n=1]) were reported in 4 (10%) patients.
      • The rate of ARRs was 15% (n=6), all were grade 1-2 in severity.
  • Cohort 3a5:
    • The ORR was 64% (95% CI, 31-89), and median PFS was NE in the amivantamab SC plus paclitaxel combination cohort 3a (n=11), as included in Table: Antitumor Activity in the Amivantamab SC plus Paclitaxel Combination Cohort 3a.
    • The initial dose level (DL0) combination was identified as the recommended phase 2 combination dose (RP2CD).
      • Dose-limiting toxicities (DLTs) were reported in 1 of 7 evaluable patients (grade 3 mucositis and fatigue, both resolved).
    • The safety profile in cohort 3a (n=11) was consistent with those of amivantamab SC and paclitaxel, as included in Table: Safety Profile for the Amivantamab SC plus Paclitaxel Combination Cohort 3a.
      • 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.
  • Cohort 6 (n~40) is evaluating perioperative amivantamab SC plus pembrolizumab in treatment-naïve patients with resectable, locally advanced human papillomavirus (HPV)-unrelated HNSCC. Results are not yet available.6

ongoing clinical study

OrigAMI-4 Study

Study Design/Methods

  • Ongoing, phase 1b/2, nonrandomized, open-label, multiarm, 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 or locally advanced HNSCC.2-6
  • The study includes cohorts of patients who had disease progression on/after 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, 5, and 6).2-6
  • Prophylactic management of dermatologic adverse events (AEs) was optional and left to the discretion of the treating investigator.3 
  • The study design is shown in Figure: OrigAMI-4 Study Design.

OrigAMI-4 Study Design2-6

OrigAMI-4 (ClinicalTrials.gov Identifier: NCT06385080).
Abbreviations: AUC, area under the concentration-time curve; BW, body weight; C, cycle; CBR, clinical benefit rate; CPS, combined positive score; 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; SD, stable disease; 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.
cOther systemic therapies were permitted if they were given as part of treatment for locally advanced disease with curative intent, were completed ≥6 months prior to the first study treatment administration, and did not result in disease progression within 6 months of completion.
dC1D1: 1600 mg (or 2240 mg if BW ≥80 kg); C1D8 and C1D15: 2400 mg (or 3360 mg if BW ≥80 kg); C2D1 (and Q3W thereafter): 2400 mg (or 3360 mg if BW ≥80 kg). Amivantamab SC was manually injected in the abdomen for all cohorts.
eOn D1 of each 21-day cycle.
fThe RP2CD of amivantamab SC will be determined with SET.
gConfirmed by SET in cohort 3A.
hOn D1 of C1-C6.
iNeoadjuvant amivantamab SC plus pembrolizumab will be administered prior to surgery (2 cycles). Following surgery, patients will receive adjuvant radiation (with or without cisplatin) plus pembrolizumab (3 cycles), followed by adjuvant amivantamab SC plus pembrolizumab (12 cycles).
jThe maximum required washout is 28 days.
kDefined as the percentage of patients with a confirmed response or durable SD at the second disease assessment.

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 HPV-unrelated patients with R/M HNSCC in the safety population who had received ≥1 prior line of therapy and were treated with ≥1 dose of amivantamab SC monotherapy, with a median follow-up of 3.5 months (range, 0-13.4).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
Efficacy Population (n=38)a
Safety Population (n=86)
Median age, years (range)
67 (30-79)
63.5 (30-81)
   <65 years, n (%)
16 (42)
46 (53)
   ≥65 to <75 years, n (%)
16 (42)
30 (35)
   ≥75 years, n (%)
6 (16)
10 (12)
Sex, n (%)
   Male
27 (71)
65 (76)
   Female
11 (29)
21 (24)
Race, n (%)
   Asian
17 (45)
39 (45)
   White
19 (50)
37 (43)
   Black or African American
0
1 (1)
   Not reported/unknown
2 (5)
9 (10)
Region, n (%)
   Eastern Asia
15 (39)
36 (42)
   North America
14 (37)
27 (31)
   Europe
7 (18)
21 (24)
   Southeastern Asia
2 (5)
2 (2)
Median body weight, kg (range)
63 (43-96)
61 (40-96)
   <80 kg, n (%)
35 (92)
78 (91)
   ≥80 kg, n (%)
3 (8)
8 (9)
ECOG PS, n (%)
   0
14 (37)
28 (33)
   1
24 (63)
58 (67)
Median time from initial head and neck diagnosis to first dose, months (range)
27 (4-270)
22 (3-270)
Median time from metastatic disease diagnosis to first dose, months (range)
12 (1-42)
10 (0-43)
Primary tumor location, n (%)
   Hypopharynx
4 (11)
13 (15)
   Larynx
10 (26)
21 (24)
   Oropharynxb
4 (11)
10 (12)
   Oral cavity
20 (53)
42 (49)
Stage at screening, n (%)
   III
2 (5)
2 (2)
   IVA
9 (24)
18 (21)
   IVB
4 (11)
12 (14)
   IVC
23 (61)
54 (63)
Site of recurrence/metastasis,c n (%)
   Bone
7 (21)
14 (17)
   Head and neck
16 (47)
51 (62)
   Liver
0
5 (6)
   Local lymph node
11 (32)
33 (40)
   Distant lymph node
9 (26)
20 (24)
   Lung
21 (62)
45 (55)
   Skin
1 (3)
1 (1)
   Other
7 (21)
17 (21)
≥1 prior therapy,c n (%)
   Prior systemic therapyd
38 (100)
86 (100)
   Prior radiotherapy
35 (92)
76 (88)
   Prior related surgery
33 (87)
71 (83)
Abbreviations: ECOG PS, Eastern Cooperative Oncology Group performance status; PD-L1, programmed cell death-ligand 1; R/M, recurrent/metastatic; SC, subcutaneous.
an=34 for time since metastatic disease diagnosis to first dose and site of R/M.
ᵇAll patients with oropharynx cancer (n=10; 100%) had confirmed p16-negative status.
ᶜPatients could be counted in >1 category.
dPrior systemic therapy included anti-PD-L1 checkpoint inhibitor and platinum-based chemotherapy; 39 (45%) patients had received prior taxane-based chemotherapy for R/M disease.
Note: Total may not sum to 100% due to rounding.
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 of 86 enrolled 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.
    • The remaining 48 patients continued to receive treatment, as they had either not had their first disease assessment or had insufficient follow-up to reach their second disease assessment.
    • Treatment was discontinued due to progressive disease (n=23; 27%), AEs (n=9; 10%), and patients refusing further treatment (n=1; 1%).
  • Among the efficacy population3:
    • In the R/M setting, 17 patients received 1 prior line of therapy and 19 received 2 prior lines.
    • Majority of patients (23 of 38; 61%) received prior immunotherapy with platinum-based chemotherapy (18 of 23 also received taxane or fluorouracil); 8 of 38 (21%) patients received prior immunotherapy with nonplatinum-based chemotherapy, and 7 of 38 (18%) patients received immunotherapy as monotherapy either before or after platinum-based chemotherapy.
    • Site of recurrence data were available for 34 patients: locoregional only disease (n=5; 15%), distant only disease (n=10; 29%), and both (n=19; 56%).
  • As of the data cutoff, 16 of 38 (42%) efficacy-evaluable patients and 11 of 17 (65%) confirmed responders remained on amivantamab SC monotherapy.3

Antitumor Activity in the Amivantamab SC Monotherapy Cohort 13
Efficacy Outcome
Cohort 1
Efficacy Population (n=38)
Median follow-up, months (range)
8.3 (1.1a-13.4)
Investigator-assessed response
  Confirmed ORR,b % (95% CI)
45 (29-62)
   Best response, n (%)
      CR
1 (3)
      PR
16 (42)
      SD
17 (45)
      PD
2 (5)
      Not evaluable
2 (5)
   Median time to first response, weeks (range)
6.4 (5.7-18.3)
   Confirmed CBR,c % (95% CI)
76 (60-89)
      Median DOR,d months (95% CI)
7.2 (5.3-NE)
         DOR ≥6 months,d n (%)
8 (47)
Median PFS, months (95% CI)
6.8 (4.2-9)
Median OS, months
NR
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.
aThe lower value in the range was from a censored observation.
bORR was defined as the percentage of patients achieving confirmed CR or PR.
cCBR was defined as the percentage of patients achieving confirmed CR, PR, or durable SD (≥11 weeks) at the second assessment.
dDOR was defined as the time from confirmed CR or PR until the date of progression or death and was measured among the 17 confirmed responders.
  • Tumor shrinkage of target lesions was observed in 31 of 38 (82%) 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.7 
Safety
  • The safety profile in cohort 1 was consistent with previous reports of amivantamab SC monotherapy (Table: Safety Summary in Cohort 1).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

Safety Summary in Cohort 13
TEAE, n (%)
Cohort 1
Safety Population (n=86)
Any TEAE (≥1 event)
79 (92)
   Grade 1-2 TEAE
39 (45)
   Grade ≥3 TEAE
40 (47)
   Serious TEAE
29 (34)
Any TEAE leading to:
   Dose interruption
37 (43)
   Dose reduction
15 (17)
   Treatment discontinuation
6 (7)
Abbreviation: TEAE, treatment-emergent adverse event.

Summary of TEAEs in Cohort 13
TEAEs (≥10%) by Preferred Term, n (%)
Cohort 1
Safety Population (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)
   Paronychia
15 (17)
1 (1)
   Diarrhea
13 (15)
0
   Pruritus
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.
aDermatitis acneiform and rash are subcategories of the grouped rash term, which occurred in 41 (48%) patients. The subcategories of dermatitis acneiform and rash are not mutually exclusive, and patients could have >1 type of rash.
  • ARRs occurred in 6 (7%) patients, all were grade 1-2 (grade 1, n=4; 5%; grade 2, n=2; 2%); no grade ≥3 events were reported.3
  • TRAEs leading to discontinuation of treatment (paronychia [n=1] and elevated alkaline phosphatase [n=1]) were reported in 2% of patients.3
  • TEAEs leading to amivantamab SC discontinuation unrelated to study treatment included pneumonia aspiration and myocardial ischemia (n=1), pneumonia aspiration (n=1), cerebrovascular accident (n=1), sudden death (n=1), and cardiac arrest and postprocedural hemorrhage (n=1).3

Results: Amivantamab SC plus Pembrolizumab Combination Cohort (Cohort 2)

  • Results are reported as of the data cutoff date of December 16, 2025.4
Patient Characteristics
  • Cohort 2 included 39 HPV-unrelated patients with R/M HNSCC who were treatment-naïve and were treated with amivantamab SC plus pembrolizumab as first-line therapy, with a median follow-up of 10.4 months (range, 1.6-12.5).4
    • Nineteen patients had received prior platinum-based systemic therapy for locally advanced disease. Platinum-refractory disease progression in ≤6 months was an exclusion criterion.
  • As of the data cutoff date, 18 (46%) patients remained on first-line treatment.4
  • Patient characteristics are included in Table: Patient Characteristics in the Amivantamab SC plus Pembrolizumab Combination Cohort 2.

Patient Characteristics in the Amivantamab SC plus Pembrolizumab Combination Cohort 24
Characteristic
Cohort 2 (n=39)
Median age, years (range)
63 (39-77)
Sex, n (%)
   Male
33 (85)
   Female
6 (15)
Race, n (%)
   Asian
18 (46)
   White
20 (51)
   Not reported
1 (3)
ECOG PS, n (%)
   0
17 (44)
   1
22 (56)
Primary tumor location, n (%)
   Hypopharynx
8 (21)
   Larynx
7 (18)
   Oropharynxa
6 (15)
   Oral cavity
18 (46)
PD-L1 CPSb
   1-19
19 (49)
   ≥20
20 (51)
Abbreviations: ECOG PS, Eastern Cooperative Oncology Group performance status; CPS, combined positive score; HPV, human papillomavirus; PD-L1, programmed cell death-ligand 1. aPatients with HPV-positive oropharyngeal cancer were excluded; all 6 patients with oropharynx as primary tumor location were HPV-negative.bPD-L1 CPS was documented by local testing using a 22C3 antibody test.
Efficacy
  • The first disease assessment was at week 9, with subsequent assessments conducted every 6 weeks.
  • The investigator-assessed confirmed ORR was 56% (95% CI, 40-72), with an ORR of 47% (95% CI, 24-71) in the combined positive score (CPS) 1-19 group and 65% (95% CI, 41-85) in the CPS ≥20 group.4
  • Tumor shrinkage of target lesions was reported in 82% of patients.4
  • Efficacy outcomes for amivantamab SC plus pembrolizumab in cohort 2 are included in Table: Antitumor Activity in the Amivantamab SC plus Pembrolizumab Combination Cohort 2.

Antitumor Activity in the Amivantamab SC plus Pembrolizumab Combination Cohort 24
Investigator-assessed
Cohort 2 (n=39)
Confirmed ORR, % (95% CI)
56 (40-72)
Best confirmed response, n (%)
   CR
4 (10)
   PR
18 (46)
   SD
11 (28)
   PD
5 (13)
   NEa
1 (3)
Time to first response,b weeks
9.7
CBR,c % (95% CI)
74 (58-87)
Median PFS, months (95% CI)
7.7 (5-NEd)
Median OS, months
NEd
Abbreviations: CBR, clinical benefit rate; CR, complete response; NE, not evaluable; PD, progressive disease; PR, partial response; SD, stable disease.aNot evaluable.bAmong all responders. First scan occurred at week 9.cDefined as the percentage of patients with a confirmed CR or PR or durable SD at the second disease assessment.dNot estimable.Note: Treatment beyond disease progression was allowed if the patient continued to derive clinical benefit.
  • Among the 22 confirmed responders, 64% remained on treatment.4
    • Five patients had their first response after 3 months of treatment.
    • Of the remaining 17 patients with sufficient follow-up, the median duration of response was not reached; 59% of patients had a duration of response of ≥6 months.
  • At 6 and 9 months, 63% and 44% of patients remained progression-free, respectively. At 6 and 9 months, 87% and 80% of patients were alive, respectively.4
  • A 46-year-old female patient with squamous cell carcinoma of the oral cavity, previously treated with surgery and adjuvant chemoradiation, presented with a large recurrent tumor in the left parotid area (PD-L1 CPS=40) and had a complete response after 7 cycles of amivantamab SC plus pembrolizumab.4
Safety
  • The safety profile in cohort 2 was consistent with those of amivantamab SC and pembrolizumab, with no new safety signals identified (Table: Safety Profile for the Amivantamab SC plus Pembrolizumab Combination Cohort 2).
  • The median treatment duration was 7.6 months (range, 0.7-12.2).4
  • TRAEs leading to discontinuation of treatment (pneumonitis [n=2]; 1 grade 2 and 1 grade 3, hepatitis [n=1]; grade 3, and Stevens-Johnson syndrome [n=1]; grade 4) were reported in 4 (10%) patients.4
  • ARRs occurred in 6 (15%) patients, all were grade 1-2.4

Safety Profile for the Amivantamab SC plus Pembrolizumab Combination Cohort 24
TEAEs (≥20%) by Preferred Term, n (%)
Cohort 2 (n=39)
All Grades
Grade ≥3
Associated with EGFR inhibition
   Rash
19 (49)
5 (13)
   Paronychia
18 (46)
2 (5)
   Dermatitis acneiform
15 (38)
2 (5)
   Stomatitis
14 (36)
2 (5)
Associated with MET inhibition
   Hypoalbuminemia
16 (41)
2 (5)
   Peripheral edema
8 (21)
0
Other
   AST increased
15 (38)
1 (3)
   ALT increased
14 (36)
2 (5)
   Fatigue
11 (28)
1 (3)
   Hypothyroidism
10 (26)
0
   Constipation
9 (23)
0
   Hypomagnesemia
8 (21)
0
   Pneumoniaa
8 (21)
6 (15)
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; EGFR, epidermal growth factor receptor; MET, mesenchymal-epithelial transition; TEAE, treatment-emergent adverse event.aIn addition, pneumonitis and pneumonia aspiration were each reported in 3 (8%) patients (1 patient, grade ≥3).

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)
   Oropharynx
1 (9)
   Oral cavity
8 (73)
Abbreviation: SC, subcutaneous.
DLTs
  • The 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
  • 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 February 2026.

 

References

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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 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 2026 February 17]. Available from: https://www.clinicaltrials.gov/study/NCT06385080 NLM Identifier: NCT06385080.  
3 Harrington KJ, Rosenberg AJ, Yang M-H, et al. Subcutaneous amivantamab in recurrent/metastatic head and neck squamous cell cancer after disease progression on checkpoint inhibitor and chemotherapy: preliminary results from the phase 1b/2 OrigAMI-4 study. Oral Oncol. 2025;171:107791.  
4 Mehra R, Kao H-F, Wang H-M, et al. Amivantamab plus pembrolizumab in previously untreated recurrent/metastatic head & neck squamous cell cancer: results from the phase 1b/2 OrigAMI-4 study. Oral Presentation presented at: Multidisciplinary Head and Neck Cancers Symposium (MHNCS); February 19-21, 2026; Palm Desert, CA.  
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.  
6 Adkins D, Haddad RI, Swiecicki P, et al. Neoadjuvant and adjuvant amivantamab plus pembrolizumab in resectable, locally advanced HPV-unrelated head & neck squamous cell cancer: cohort 6 of the phase 1b/2 OrigAMI-4 study. Poster presented at: Multidisciplinary Head and Neck Cancers Symposium (MHNCS); February 19-21, 2026; Palm Desert, CA.  
7 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.