OrigAMI-5 - A Phase 3, Randomized, Open-Label, Multicenter Study of Amivantamab in Addition to Carboplatin and Pembrolizumab, Compared to Standard of Care Platinum and Pembrolizumab and 5-FU, in Participants With Treatment-Naïve Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (61186372HNC3001).

Studio Clinico

Patologia: Tumori della testa e del collo

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: Sì

Fase di studio: III

Linee di trattamento: Prima linea

Criteri di inclusione: 

- Be ≥18 years of age (or the legal age of majority in the jurisdiction in which the study is taking place, whichever is greater).
- Have an ECOG performance status of 0 or 1.
Criterion modified per Amendment EEA-1.
3.1 Have histologically or cytologically confirmed R/M HNSCC that is considered incurable by local therapies.
- The eligible primary tumor locations are the oral cavity, oropharynx, hypopharynx, or larynx.
- Must not have a primary tumor site of nasopharynx (any histology) or primary tumor of unknown location.
- Must have documented local testing results per local regulations using a 22C3 antibody assay for PD-L1 status to determine the CPS score within 6 months prior to C1D1; participants must have PD-L1 CPS ≥1 to be considered eligible.
The local test must be performed in accordance with local guidelines using an FDA-approved test or laboratory-developed test that is validated in a CLIAcertified laboratory (sites in the US) or an accredited local laboratory (sites outside of the US). In the EU, the local test must be CE-marked or an in-house laboratory-developed test from health institutions in the EU in accordance with Article 5(5) of the IVDR2071/746, as amended. Tissue used for CPS testing should be obtained at or after diagnosis of R/M disease and prior to any provision of systemic therapy for R/M disease. Report documenting PD-L1 status must be included in participant records and a de-identified copy submitted to sponsor during the screening period.
- HPV status must be known for participants with primary tumor location in oropharynx via p16 test, HPV DNA test, or high-risk HPV ISH. Any known p16, HPV DNA, or high-risk HPV ISH status of tumor must be negative.
Be treatment-naïve for systemic therapy in the R/M setting. Systemic therapy which was completed more than 6 months prior to signing consent, if given as part of treatment for locally advanced disease with curative intent, is allowed. The participant must not have had disease progression within 6 months of completion of curative systemic therapy for locally advanced disease.

- The participant must be treatment-naïve to any prior anti-EGFR therapy and anti- MET therapy in any setting.
- The participant may have received anti-PD-1/PD-L1/PD-L2 agents for locally advanced disease with curative intent if given >12 months prior to enrollment.
Have measurable disease according to RECIST v1.1. If only one measurable lesion exists, it may be used for the screening biopsy as long as baseline tumor assessment scans are performed ≥7 days after the biopsy and if lesion remains acceptable as a target
lesion after that time. Tumor lesions situated in a previously irradiated area are considered measurable if progression following radiation has been demonstrated in such lesions.
Consent to a screening biopsy or provide archival tissue sample per protocol-defined specifications. Participants must have a screening biopsy within 28 days prior to C1D1 or archival tissue that was obtained within 6 months of diagnosis of R/M disease. Tissue must be submitted prior to C1D1.
Criterion modified per Amendment EEA-1.
7.1 While on study treatment and for 10up to 14 months after the last dose of study treatment, a participant must:
   a. Not breastfeed or be pregnant.
   b. Not donate gametes (ie, eggs or sperm) or freeze for future use for the purposes of assisted reproduction.
   c. Wear an external condom.
   d. If of childbearing potential, participant must:
      o have a negative highly sensitive (eg, beta-human chorionic gonadotropin [β- hCG]) serum pregnancy test at screening and within 72 hours of the first dose of study treatment and must agree to further pregnancy tests.
      o practice at least 1 highly effective method of contraception; if oral contraceptives are used, a barrier method of contraception must also be used.
   e. If a participant’s partner is of childbearing potential, the partner must practice a highly effective method of contraception unless the participant is vasectomized.
Participants should consider preservation of gametes prior to study treatment as anticancer treatments may impair fertility.
Must sign an ICF indicating that the participant understands the purpose and procedures required for the study. If the participant is unable to read or write, an impartial witness must be present (which includes reading and explaining all written information) and must date and sign the ICF after oral consent of the participant. Where local regulations require, a separate ICF may be used for the required DNA component of the study.
9. Must be willing and able to adhere to the lifestyle restrictions specified in this protocol.

Criteri di esclusione: 

- Has an uncontrolled illness, including but not limited to the following:
   a. Diabetes.
   b. Ongoing or active infection (includes infection requiring treatment with antimicrobial therapy [participants will be required to complete antibiotics 1 week prior to starting study treatment]) or diagnosed or suspected viral infection.
   c. Active bleeding diathesis (including active bleeding from primary tumor, or recent bleeding within 2 weeks prior to first administration of study treatment requiring medical or surgical intervention).
   d. Impaired oxygenation requiring continuous oxygen supplementation.
   e. Psychiatric illness/social situation that would limit compliance with study requirements.
   f. Active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
   g. Participant has had an allogeneic tissue/solid organ transplant.
Has untreated brain metastases or history of known presence of leptomeningeal disease.
Notes: Participants with definitively, locally treated metastases that are clinically stable and asymptomatic for at least 4 weeks and who are off or receiving low-dose corticosteroid treatment (≤10 mg prednisone or equivalent) for at least 4 weeks prior to
study treatment are eligible, provided they have not used steroids for at least 7 days prior to study treatment.
Has a history of (non-infectious) ILD/pneumonitis/pulmonary fibrosis, has current ILD/pneumonitis, or where suspected ILD/pneumonitis/pulmonary fibrosis cannot be ruled out by imaging at screening.
Has a history of clinically significant cardiovascular disease including, but not limited to:
   a. Diagnosis of deep vein thrombosis or pulmonary embolism within 8 weeks prior to the first dose of study treatment or any of the following within 6 months prior to the first dose of study treatment: myocardial infarction, unstable angina,
stroke, transient ischemic attack, coronary/peripheral artery bypass graft, or any acute coronary syndrome. Clinically non-significant thrombosis, such as nonobstructive catheter-associated clots, are not exclusionary.
   b. Prolonged QTcF interval >480 msec or clinically significant cardiac arrhythmia or electrophysiologic disease (eg, placement of implantable cardioverter defibrillator or atrial fibrillation with uncontrolled rate).
Note: Participants with cardiac pacemakers who are clinically stable are eligible.
   c. Uncontrolled (persistent) hypertension: systolic blood pressure >180 mm Hg; diastolic blood pressure >100 mm Hg.
   d. Congestive heart failure defined as New York Heart Association (NYHA) class III, IV or Hospitalization for congestive heart failure (any NYHA class) within 6 months of study enrollment.
   e. Pericarditis/clinically significant pericardial effusion.
   f. Myocarditis.
Renal function:
   Have an estimated glomerular filtration rate <50 mL/min, based on the MDRD 4-variable formula (Section 10.8) during the screening period and on the day of the start of study treatment.
Hepatic function:
   Participants are excluded if they have the following lab values:
      a. AST ≥3 x ULN (≥5 x ULN if liver metastases are present).
      b. ALT ≥3 x ULN (≥5 x ULN if liver metastases are present).
      c. Total bilirubin ≥1.5x ULN: participants with congenital nonhemolytic hyperbilirubinemia such as Gilbert’s syndrome can enroll if conjugated bilirubin is within normal limits.
For hematological values, must not have:
      a. Hemoglobin <9g/dL
      b. Absolute neutrophil count <1.5x109/L
      c. Platelets <100x109/L
Participant must have adequate organ and bone marrow function as above, without history of red blood cell transfusion, platelet transfusion, use of granulocyte colonystimulating factor (G-CSF) within 7 days prior to the date of the laboratory test.
Thyroid function laboratory values not within the normal range.
Note: If TSH is not within normal limits, the participant may still be eligible if triiodothyronine (either total or free) and free thyroxine are within normal limits. If TSH is above the upper normal limit, a participant may still be eligible if asymptomatic with
no hypothyroidism symptoms or on thyroid supplementation.
Active hepatitis of infectious origin.
      a. Seropositive for hepatitis B: defined by a positive test for hepatitis B surface antigen [HBsAg]. Participants with resolved infection (ie, participants who are HBsAg negative with positive antibodies to total hepatitis B core antigen [HBcAb]) must be screened using RT-PCR measurement of HBV DNA levels. Those who are RT-PCR positive will be excluded. Participants with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a
known history of prior HBV vaccination, do not need to be tested for HBV DNA by RT-PCR.
      b. Known hepatitis C infection or positive serologic testing for hepatitis C virus (anti-HCV) antibody. Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled only if a confirmatory negative hepatitis C RNA  test is obtained at screening or within 3 months prior to first dose of study treatment.
      c. Other clinically active liver disease of infectious origin.
Current or chronic history of non-infectious liver disease. This includes (but is not limited to) drug- or alcohol-related liver disease, metabolic dysfunction-associated steatohepatitis, auto-immune hepatitis, hemochromatosis, Wilson’s disease, alpha-1
antitrypsin deficiency, primary biliary cholangitis, primary sclerosing cholangitis, or any other liver disease considered clinically significant by the investigator.
Have a prior malignancy (other than the disease under study) in which its natural history or treatment is likely to interfere with any study endpoints of safety or the efficacy of the study treatment(s). The occurrence must be reviewed and agreed to with the sponsor’s medical monitor. Refer to Section 10.7 for more details.
Has known allergies, hypersensitivity, contraindications, or intolerance to excipients of:
      a. Amivantamab (refer to the IB, experimental arm)
      b. Pembrolizumab (refer to product label)
      c. Carboplatin (refer to product label)
      d. Cisplatin (refer to product label)
      e. 5-FU (refer to product label, control arm); participants with known complete absence of DPD activity are ineligible. Testing for DPD deficiency must be performed in accordance with local guidelines.
      f. Hyaluronidase as, or will have, any of the following:
        a. An invasive operative procedure with entry into a body cavity, including feeding tube placement and tracheostomy, within 4 weeks or without complete recovery before the first administration of study treatment.
        b. Significant traumatic injury within 3 weeks before the start of the first administration of study treatment (all wounds must be fully healed prior to C1D1).
        c. Expected major surgery while the investigational agent is being administered or
within 6 months after the last dose of study treatment.

Schema di trattamento: 

Arm A (experimental arm): pembrolizumab, amivantamab SC (1,600 mg for BW <80 kg; 2,240 mg for BW ≥80), and carboplatin (Q3W starting from Cycle 1 onwards)

Arm B (comparator arm): pembrolizumab, 5-FU, and platinum therapy (carboplatin or cisplatin)
(Q3W starting from Cycle 1 onwards)

Trattamento sperimentale: 

Amivantamab SC + Carboplatino + Pembrolizumab

Trattamento di controllo: 

Pembrolizumab + Platinum + 5-FU

Obiettivi primari dello studio: 

The primary objective of OrigAMI-5 is to compare anti-tumor activity (OS and ORR) of amivantamab SC in addition to pembrolizumab and carboplatin versus pembrolizumab, 5-FU, and platinum (carboplatin or cisplatin) therapy in participants with R/M HNSCC who are treatment-naïve in the R/M setting.

Obiettivi secondari dello studio: 

Secondary objectives will further evaluate safety and other measures of efficacy, as well as PROs and PK.

Centri partecipanti

Nord Italia

Centro Italia

Sud Italia e isole

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2025-521917-24

Data di inserimento: 27.04.2026

Promotore

Janssen Research & Development, LLC

Principal Investigator ITALIA

Riferimento: Dr. - -

Telefono: 00000

Email: na@na.it

Localita: na