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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: 09/22/2026

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 and 4), prior checkpoint inhibitor therapy (cohort 3) or were treatment-naïve (cohorts 2, 5, and 6). Enrollment is planned for approximately 287 patients.2-7
  • Preliminary analysis results were previously reported at a median follow-up of 3.5 months (data cutoff: July 01, 2025).3
  • Cohort 16:
    • The blinded independent central review (BICR)-assessed objective response rate (ORR) was 42% (95% confidence interval [CI], 32-52), and the investigator-assessed ORR was 47% (95% CI, 37-57) in the amivantamab SC monotherapy cohort 1 (n=102), as included in Table: Efficacy Outcomes in the Amivantamab SC Monotherapy Cohort 1.6,8
    • Median progression-free survival (PFS) and overall survival (OS) were 6.8 months (95% CI, 5.2-8.3) and 12.5 months (95% CI, 10.2-16.8), respectively.6 
    • The safety profile in cohort 1 is included in Table: Safety Summary in Cohort 1.8  
      • Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 60% of patients; serious adverse events (AEs) occurred in 39% of patients.6
      • The most common TEAEs were hypoalbuminemia (50%), rash (37%), dermatitis acneiform (34%), and paronychia (34%), and were mostly grade 1-2 in severity.6,8
      • Administration-related reactions (ARRs) occurred in 15% of patients (grade 1, 9%; grade 2, 6%).6
      • Treatment-related adverse events (TRAEs) leading to discontinuation of amivantamab were reported in 8% of patients.6
  • Cohort 27:
    • In the amivantamab SC plus pembrolizumab intravenous (IV) combination cohort 2 (n=39), the investigator-assessed ORR was 59% (95% CI, 42-74), median PFS was 7.7 months (95% CI, 5-not reached [NR]), and median OS was NR
      (95% CI, 13.6-NR), as included in Table: Efficacy Outcomes in the Amivantamab SC plus Pembrolizumab IV Combination Cohort 2.7
    • The safety profiles of amivantamab SC and pembrolizumab IV were consistent with previous reports of the individual agents. All patients experienced ≥1 TEAE, as shown in Table: Safety Summary in Cohort 2.7
      • ARRs occurred in 18% patients, all were grade 1-2.
      • TRAEs leading to discontinuation of all study treatments occurred in 5 (13%) patients and included pneumonitis, hepatitis, immune-mediated cholangitis, rash, and Stevens-Johnson syndrome (n=1 each).
  • Cohort 3a4:
    • 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.4
    • The initial dose level (DL0) combination was identified as the recommended phase 2 combination dose (RP2CD).4
      • 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.4
      • 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.4
  • 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.5

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 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 Design2,4-8

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; CT, computed tomography; 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; MRI, magnetic resonance imaging; 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.

cCohorts 1 and 4 include patients with prior PD‑1/PD‑L1 inhibitor therapy and platinum‑based chemotherapy in combination or as separate lines of therapy for R/M disease. Cohorts 3a and 3b include patients with prior PD‑1/PD‑L1 inhibitor therapy.

dOther 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.
eC1D1: 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.
fOn D1 of each 21-day cycle.
gThe RP2CD of amivantamab SC will be determined with SET.
hConfirmed by SET in cohort 3A.
iOn 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).
kThe maximum required washout is 28 days.
lDefined as the percentage of patients with a confirmed response or durable SD at the second disease assessment.

Note: Disease was assessed at baseline and every 6 weeks (±1 week) for 1 year, then every 9 weeks thereafter using CT or MRI per RECIST v1.1. Brain imaging by MRI (or CT if MRI was contraindicated) at baseline was required for all patients with a history of brain metastasis or suspected brain metastasis, with repeat scans performed every 12 weeks (±1 week).

Results: Amivantamab SC Monotherapy Cohort (Cohort 1)

  • Results are reported as of the data cutoff date of March 18, 2026.6
Patient Characteristics

Patient Characteristics in the Amivantamab SC Monotherapy Cohort 16 
Characteristic
Cohort 1
(n=102)
Median age, years (range)
63 (30-81)
   <65 years, n (%)
56 (55)
   ≥65 to <75 years, n (%)
35 (34)
   ≥75 years, n (%)
11 (11)
Sex, n (%)
   Male
79 (77)
   Female
23 (23)
Race, n (%)
   Asian
45 (44)
   White
42 (41)
   Black or African American
1 (1)
   Not reported/unknown
14 (14)
Region, n (%)
   Eastern Asia
42 (41)
   North America
29 (28)
   Europe
29 (28)
   Southeastern Asia
2 (2)
Median body weight, kg (range)
61.5 (40-96)
   <80 kg, n (%)
93 (91)
   ≥80 kg, n (%)
9 (9)
ECOG PS score, n (%)
   0
34 (33)
   1
68 (67)
History of smoking, n (%)
   Yes
72 (71)
   No
30 (29)
Median time from initial head and neck diagnosis, months (range)
21.2 (3.2-269.7)
Median time from recurrent/metastatic disease diagnosis, months (range)
8.9 (0.4-43.7)
Primary tumor location, n (%)
   Oral cavity
48 (47)
   Larynx
24 (24)
   Hypopharynx
16 (16)
   Oropharynx
14 (14)
Stage at screening, n (%)
   III
4 (4)
   IVA
22 (22)
   IVB
11 (11)
   IVC
65 (64)
Site of recurrence/metastasisa, n (%)
   Head and neck
66 (65)
   Lung
53 (52)
   Local lymph node
40 (39)
   Distant lymph node
24 (24)
   Bone
12 (12)
   Liver
7 (7)
   Skin
3 (3)
   Other
19 (19)
Patients with ≥1 prior therapy, n (%)
   Prior systemic therapy
102 (100)
      1 prior line of therapy
53 (52)
      2 prior lines of therapy
49 (48)
Abbreviations: ECOG PS, Eastern Cooperative Oncology Group performance status; SC, subcutaneous.aPatients can be counted in >1 category.

Summary of Patient Disposition in the Amivantamab SC Monotherapy Cohort 18
Cohort 1
(n=102)
Received amivantamab SC, n
102
Disposition, n (%)
   Ongoing treatment
32 (31)
   Discontinued treatment
70 (69)
      Disease progression
54 (53)
      Adverse event
15 (15)
         Related adverse event
8 (8)
      Withdrawal by patient
1 (1)
Abbreviations: SC, subcutaneous
Efficacy

Efficacy Outcomes in the Amivantamab SC Monotherapy Cohort 16,8
Cohort 1
(n=102)
BICR-assessed response
Investigator-assessed response
Median follow-up, months (range)
11.8 (1.1-21.9)
Confirmed ORR, % (95% CI)
42 (32-52)
47 (37-57)
Best response, n (%)
   CR
15 (15)
7 (7)
   PR
28 (27)
41 (40)
   SD
36 (35)a
39 (38)
   PD
16 (16)
9 (9)
   NE
7 (7)
6 (6)
CBR, % (95% CI)b
63 (53-72)
74 (64-82)
Median DOR, months (95% CI)
NR (6.9-NR)c
9.5 (6.7-NR)d
   DOR ≥6 months, n (%)
24 (56)
26 (54)
Abbreviations: BICR, blinded independent central review; CI, confidence interval; CBR, clinical benefit rate; CR, complete response; DOR, duration of response; NE, not evaluable; NR, not reached; ORR, objective response rate; PD, progressive disease; PR, partial response; SC, subcutaneous; SD, stable disease.
aIncludes non-CR/non-PD in patients with only non-target lesions at baseline and no evidence of disease in patients with no target or non-target lesions at baseline. bCBR is defined as the percentage of patients achieving a CR or PR, or durable SD (at the second disease assessment).cAmong 43 confirmed responders.dAmong 48 confirmed responders.

Confirmed ORR by BICR Across Prespecified Subgroups in Cohort 18
Subgroup
n/N
ORR (95% CI)
Overall
43/102
42 (32-52)
Age
   <65 years
29/56
52 (38-65)
   ≥65 years
14/46
30 (18-46)
   <75 years
38/91
42 (32-53)
   ≥75 years
5/11
45 (17-77)
Sex
   Male
32/79
41 (30-52)
   Female
11/23
48 (27-69)
Body weight
   <80 kg
42/93
45 (35-56)
   ≥80 kg
1/9
11 (0-48)
Race
   Asian
19/45
42 (28-58)
   Non-Asian
15/43
35 (21-51)
ECOG PS
   0
15/34
44 (27-62)
   1
28/68
41 (29-54)
History of smoking
   Yes
29/72
40 (29-53)
   No
14/30
47 (28-66)
Primary tumor location
   Oral cavity
27/48
56 (41-71)
   Non-oral cavity
16/54
30 (18-44)
Prior lines of therapya
   1
23/53
43 (30-58)
   2
20/49
41 (27-56)
Abbreviations: BICR, blinded independent central review; CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; ORR, objective response rate.aPrior lines of therapy was not a prespecified subgroup.

PFS and OS with Amivantamab SC Monotherapy Cohort 16 
Endpoint
Cohort 1
(n=102)
Median PFSa, months (95% CI)
6.8 (5.2-8.3)
   PFS rate at 6 months, % (95% CI)
53 (43-62)
   PFS rate at 12 months, % (95% CI)
23 (13-35)
Median OS, months (95% CI)
12.5 (10.2-16.8)
   OS rate at 6 months, % (95% CI)
78 (69-85)
   OS rate at 12 months, % (95% CI)
54 (42-64)
Abbreviations: CI, confidence interval; OS, overall survival; PFS, progression-free survival.aAssessed by investigator.
  • Antitumor activity was observed across genetic aberrations. No clear associations were identified, with the analysis being limited by the small sample size.6 
  • 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.9 
Safety

Safety Summary in Cohort 18  
TEAE, n (%)
Cohort 1
(n=102)
Any TEAE
102 (100)
Any grade ≥3 TEAE
61 (60)
   Any grade 5
6 (6)a
Any serious TEAE
40 (39)
Any TEAE leading to:
   Dose interruption
52 (51)
   Dose reduction
23 (23)
   Discontinuation
17 (17)
      Treatment-related discontinuation
8 (8)b
Abbreviations: AE, adverse event; TEAE, treatment-emergent adverse event.aFor grade 5 TEAEs, 1 patient had treatment-related pneumonitis resulting in death. Five additional deaths due to AEs occurred, which were considered unrelated to amivantamab. bEight patients discontinued amivantamab due to treatment-related AEs for the following reasons: rash or pustular rash (n=2), blood alkaline phosphate increased (n=1), folliculitis (n=1), interstitial lung disease (n=1), paronychia (n=1), pneumonitis (n=1), stomatitis (n=1).
  • Most TEAEs were grade 1-2 in severity.6 The incidence of TEAEs (≥10%) by preferred term is included in Table: Summary of TEAEs in Cohort 1.8 
  • ARRs occurred in 15% of patients and were either grade 1 (9%) or grade 2 (6%).6

Summary of TEAEs in Cohort 18 
TEAEs (≥10%) by Preferred Term, n (%)
Cohort 1
(n=102)
All Grades
Grade ≥3
Hypoalbuminemia
51 (50)
5 (5)
Rash
38 (37)
3 (3)
Dermatitis acneiform
35 (34)
6 (6)
Paronychia
35 (34)
2 (2)
Fatigue
29 (28)
4 (4)
Stomatitis
29 (28)
2 (2)
Hypocalcemia
25 (25)
1 (1)
Peripheral edema
24 (24)
1 (1)
Anemia
22 (22)
5 (5)
Weight decreased
18 (18)
1 (1)
Hypomagnesemia
18 (18)
1 (1)
Nausea
17 (17)
0
AST increased
16 (16)
3 (3)
Diarrhea
16 (16)
0
Lymphopenia
15 (15)
9 (9)
ALT increased
15 (15)
4 (4)
Pruritus
15 (15)
2 (2)
Administration-related reaction
15 (15)
0
Decreased appetite
15 (15)
0
Hypokalemia
15 (15)
3 (3)
Dyspnea
13 (13)
3 (3)
Pneumonia
12 (12)
6 (6)
Insomnia
12 (12)
0
Asthenia
11 (11)
0
Dizziness
11 (11)
0
Constipation
10 (10)
0
Pyrexia
10 (10)
1 (1)
Hypotension
10 (10)
0
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; TEAE, treatment-emergent adverse event.
  • The incidence of TRAEs is shown in Table: TRAEs in Cohort 1.8
  • TRAEs leading to discontinuation of amivantamab were reported in 8% of patients.6

TRAEs in Cohort 18 
TRAEs (≥10%), n (%)
Cohort 1
(n=102)
Hypoalbuminemia
41 (40)
Rash
38 (37)
Dermatitis acneiform
34 (33)
Paronychia
34 (33)
Stomatitis
27 (26)
Fatigue
20 (20)
Pruritus
15 (15)
Administration-related reaction
15 (15)
Diarrhea
12 (12)
Hypocalcemia
12 (12)
Peripheral edema
12 (12)
Hypomagnesemia
12 (12)
Hypokalemia
11 (11)
Decreased appetite
10 (10)
Abbreviations: TRAE, treatment-related adverse event.

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

  • Results are reported as of the data cutoff date of March 18, 2026.7
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 IV as first-line therapy.7
  • Patient characteristics are included in Table: Patient Characteristics in the Amivantamab SC plus Pembrolizumab IV Combination Cohort 2.7
    • Nineteen patients had received prior platinum-based systemic therapy for locally advanced disease.
  • As of the data cutoff date7:
    • The median follow-up was 13.6 months (range, 1.6-15.8).
    • Treatment duration was 6.9 months (range, 0.7-15.2) with amivantamab SC and 7.2 months (range, 0.7-15.2) with pembrolizumab IV.
    • Treatment was ongoing in 14 (36%) patients.

Patient Characteristics in the Amivantamab SC plus Pembrolizumab IV Combination Cohort 27
Characteristic
Cohort 2
(n=39)
Median age, years (range)
63 (39-77)
   <65 years, n (%)
22 (56)
   ≥65 to <75 years, n (%)
15 (38)
   ≥75 years, n (%)
2 (5)
Sex, n (%)
   Male
33 (85)
   Female
6 (15)
Race, n (%)
   White
20 (51)
   Asian
18 (46)
   Not reported
1 (3)
Region, n (%)
   Europe
17 (44)
   Eastern Asia
13 (33)
   Southeastern Asia
5 (13)
   North America
4 (10)
Median body weight, kg (range)
63 (38-92)
   <80 kg, n (%)
34 (87)
   ≥80 kg, n (%)
5 (13)
ECOG PS, n (%)
   0
17 (44)
   1
22 (56)
Median time from initial diagnosis to first dose, months (range)
19 (0.7-286.6)
Median time from recurrent/metastatic diagnosis to first dose, monthsa (range)
1.5 (0.5-98.9)
Primary tumor location, n (%)
   Oral cavity
18 (46)
   Hypopharynx
8 (21)
   Larynx
7 (18)
   Oropharynxb
6 (15)
Stage at screening
   I
1 (3)
   II
2 (5)
   IVA
10 (26)
   IVB
5 (13)
   IVC
21 (54)
Site of recurrence/metastasisa,c
   Head and neck
24 (63)
   Distant lymph node
11 (29)
   Lung
11 (29)
   Local lymph node
10 (26)
   Bone
3 (8)
   Liver
2 (5)
   Pelvis
1 (3)
   Other
3 (8)
Location of recurrence/metastasisa
   Locoregional only
18 (47)
   Distant only
10 (26)
   Locoregional and distant
10 (26)
Abbreviations: ECOG PS, Eastern Cooperative Oncology Group performance status; IV, intravenous; SC, subcutaneous. aReported in 38 patients.bAll patients with an oropharyngeal tumor were p16 negative.cPatients could be included in >1 category.
  • Patient disposition is included in the Table: Summary of Patient Disposition in the Amivantamab SC plus Pembrolizumab IV Combination Cohort 2.10

Summary of Patient Disposition in the Amivantamab SC plus Pembrolizumab IV Combination Cohort 210
Cohort 2
(n=39)
Received amivantamab SC plus pembrolizumab IV, n
39
Disposition, n (%)
   Ongoing treatment
 14 (36)
   Discontinued treatment
25 (64)
      Disease progression
15 (38)
      AE
10 (26)
         TRAEa
5 (13)
Abbreviations: AE, adverse event; IV, intravenous; SC, subcutaneous; TRAE, treatment-related adverse event.aTRAEs leading to discontinuation of all study treatments occurred in 5 (13%) patients and included pneumonitis, hepatitis, immune-mediated cholangitis, rash, and Stevens–Johnson syndrome (n=1 each).
Efficacy
  • The first disease assessment was conducted at week 9 (±1 week), with subsequent assessments performed every 6 weeks (±1 week) thereafter. After the first year, disease assessments were conducted every 9 weeks relative to cycle (C) 1 day (D) 1.7
  • Efficacy outcomes for amivantamab SC plus pembrolizumab IV in cohort 2 are included in Table: Efficacy Outcomes in the Amivantamab SC plus Pembrolizumab IV Combination Cohort 2.7

Efficacy Outcomes in the Amivantamab SC plus Pembrolizumab IV Combination Cohort 27
Endpoint
Cohort 2
(n=39)
Median follow-up, monthsa (range)
13.6 (1.6-15.8)
Investigator-assessed confirmed ORR, % (95% CI)b
59 (42-74)
Best response, n (%)
   Confirmed CR
7 (18)
   Confirmed PR
16 (41)
   SD
10 (26)
   PD
5 (13)
   NEc
1 (3)
CBR, % (95% CI)d
74 (58-87)
Median DOR, monthse (95% CI)
NR (4.1-NR)
   DOR ≥6 months, n (%)
14 (61)
Median PFSf, months (95% CI)
7.7 (5-NR)
Median OS, months (95% CI)
NR (13.6-NR)
Abbreviations: CBR, clinical benefit rate; CI, confidence interval; CR, complete response; DOR, duration of response; IV, intravenous; NE, not evaluable; 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 minimum value for the range is reported for a censored observation.bORR was defined as the percentage of patients who achieved a confirmed response.cOne patient did not have a post baseline tumor assessment, but all patients were included in the ORR analysis.dCBR was defined as the percentage of patients who achieved a confirmed response or durable SD (at the second disease assessment).eDOR was defined as the time from a confirmed response until progression or death, whichever came first; among 23 patients.fInvestigator-assessed.
  • Tumor shrinkage of target lesions was observed in 32 (82%) patients.7
  • Among the 23 patients with a confirmed response, the median time to first response was 9.6 weeks (range, 8.7-51.6). Per the protocol, the first disease assessment was conducted at week 9.7
  • At the data cutoff, 13/23 (57%) responders had an ongoing response.7
  • PFS rates were 63% (95% CI, 45-76) and 38% (95% CI, 23-53) at 6 and 12 months, respectively, while OS rates were 87% (95% CI, 72-94) and 73% (95% CI, 55-84) at 6 and 12 months, respectively.7
Safety
  • The safety profiles of amivantamab SC and pembrolizumab IV in cohort 2 were consistent with previous reports of the individual agents.7
  • All patients experienced ≥1 TEAE, as shown in Table: Safety Summary in Cohort 2.7

Safety Summary in Cohort 27
Event, n (%)
Cohort 2
(n=39)
Any TEAE
39 (100)
Grade ≥3 TEAE
28 (72)
Serious TEAE
23 (59)
Any TEAE leading to:
   Dose interruption of any study agent
32 (82)
   Dose reduction of amivantamaba
19 (49)
   Discontinuation of any study agent
11 (28)
Abbreviation: TEAE, treatment-emergent adverse event.aPer protocol, dose reductions of pembrolizumab were not permitted.
  • The incidence of TEAEs (≥15%) by preferred term is included in Table: Summary of TEAEs in Cohort 2.7
  • ARRs occurred in 18% patients, all were grade 1-2.7
  • Pneumonitis was reported in 8% of patients; 3% were grade 3.7

Summary of TEAEs in Cohort 27
TEAEs (≥15%) by Preferred Term, n (%)
All Grades
Grade ≥3
Rash
19 (49)
6 (15)
Paronychia
18 (46)
3 (8)
Hypoalbuminemia
17 (44)
3 (8)
Increased AST
15 (38)
2 (5)
Dermatitis acneiform
15 (38)
2 (5)
Increased ALT
14 (36)
2 (5)
Stomatitis
14 (36)
2 (5)
Fatigue
12 (31)
2 (5)
Hypothyroidism
11 (28)
0
Constipation
9 (23)
0
Pneumonia
9 (23)
7 (18)
Hypomagnesemia
8 (21)
0
Peripheral edema
8 (21)
0
ARR
7 (18)
0
Increased alkaline phosphatase
7 (18)
1 (3)
Diarrhea
7 (18)
1 (3)
Hypokalemia
7 (18)
1 (3)
Hyperamylasemia
6 (15)
1 (3)
Increased lipase
6 (15)
0
Nausea
6 (15)
0
Skin fissures
6 (15)
0
Decreased weight
6 (15)
0
Abbreviations: ALT, alanine aminotransferase; ARR, administration-related reaction; AST, aspartate aminotransferase; TEAE, treatment-emergent adverse event.
  • TRAEs leading to discontinuation of all study treatments occurred in 5 (13%) patients and included pneumonitis, hepatitis, immune-mediated cholangitis, rash, and Stevens-Johnson syndrome (n=1 each).7
Biomarker Analysis
  • Tumor PD-L1 expression was assessed by local testing using the PD-L1 22C3 assay and reported as combined positive score (CPS).7
  • Exploratory biomarker analyses demonstrated clinical activity across PD-L1 CPS subgroups.7
  • By local PD-L1 testing, the investigator-assessed confirmed ORR was 53%
    (95% CI, 29-76) among patients with CPS 1-19 (n=19) and 65% (95% CI, 41-85) among patients with CPS ≥20 (n=20).7
  • Complete responses were achieved in 1/19 (5%) patients with CPS 1-19 and in
    6/20 (30%) patients with CPS ≥20.7
  • Baseline circulating tumor DNA (ctDNA) analysis was performed in 38 patients; 36 had evaluable results. Two samples failed quality control, and 1 patient had no detectable ctDNA alterations.7
  • Among the 36 evaluable samples, TP53 mutations were detected in 28 (78%) patients, EGFR amplification in 5 (14%) patients, and MET amplification in 1 (3%) patient; no EGFR or MET mutations were identified.7
  • No clear association was observed between gene- or pathway-level alterations and clinical response to amivantamab SC plus pembrolizumab IV.7

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

  • Results are reported as of the data cutoff date of August 6, 2025.4
Patient Characteristics

Patient Characteristics in the Amivantamab SC plus Paclitaxel Combination Cohort 3a4
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 C1D8 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.4
  • Of the 7 DLT-evaluable patients, 1 experienced DLTs (grade 3 mucositis and fatigue, both resolved).4
Safety

Safety Profile for the Amivantamab SC plus Paclitaxel Combination Cohort 3a4
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 3a4
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.4
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.4

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 September 2026.

 

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 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 September 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 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.  
5 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.  
6 Burtness B, Rosenberg AJ, Calderon B, et al. Amivantamab in recurrent/metastatic head and neck squamous cell cancer after checkpoint inhibitor and chemotherapy: pivotal results from the phase Ib/II OrigAMI-4 study. J Clin Oncol. 2026;44(24):2271-2277.  
7 Kao H, Harrington K, Bhatia A, et al. Amivantamab plus pembrolizumab in previously untreated recurrent/metastatic head and neck squamous cell cancer: results from the phase 1b/2 OrigAMI-4 study. [Published online ahead of print September 15, 2026]. Clin Cancer Res. doi:10.1158/1078-0432.ccr-26-1372.  
8 Burtness B, Rosenberg AJ, Calderon B, et al. Supplement to: Amivantamab in recurrent/metastatic head and neck squamous cell cancer after checkpoint inhibitor and chemotherapy: pivotal results from the phase Ib/II OrigAMI-4 study. J Clin Oncol. 2026;44(24):2271-2277.  
9 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.  
10 Kao HF, Harrington K, Bhatia A, et al. Supplement to: Amivantamab plus pembrolizumab in previously untreated recurrent/metastatic head and neck squamous cell cancer: results from the phase 1b/2 OrigAMI-4 study. [Published online ahead of print September 15, 2026]. Clin Cancer Res. doi:10.1158/1078-0432.ccr-26-1372.  

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