AMIVANTAMAB for Head and neck squamous cell carcinoma

Inclusion criteria

• {"criterion_text":"- 1. Be ≥18 years of age (or the legal age of majority in the jurisdiction in which the study is taking place, whichever is greater) at the time of informed consent.\n- 9. Have at least 1 of the following: a. Serum creatinine ≤1.5×ULN b. Estimated glomerular filtration rate ≥45 mL/min, based on the MDRD 4-variable formula\n- 10. Participants are eligible 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. d. For Cohort 6 only: albumin ≥3.0 g/dL\n- 11. Participant must have adequate organ and bone marrow function as follows, without history of red blood cell transfusion, platelet transfusion, or use of granulocyte colony-stimulating factor within 7 days prior to the date of the laboratory test. Participants should have: a. Hemoglobin ≥9g/dL. b. Neutrophils ≥1.5 x 103/μL. c. Platelets ≥100 x 103/μL.\n- 12. Participants must meet the following cohort-specific requirements: Cohort 2, Cohort 5, and Cohort 6 (ie, cohorts receiving pembrolizumab): Thyroid function laboratory values within the normal range. Thyroid function laboratory values within the normal range.\n- 2. Cohorts 1 to 5: Have histologically or cytologically confirmed R/M HNSCC that is considered incurable by local therapies or for Cohort 6: have histologically or cytologically confirmed L/A HNSCC that is considered curable by surgery Cohort 1,2,3A, and 3B a. The eligible primary tumor locations are the oropharynx, oral cavity, hypopharynx, or larynx. b. Any known p16 status of tumor must be negative. Note: All participants with an oropharyngeal tumor must have results of p16 status, per local testing. c. Participants must provide local testing results of PD-L1 status, if available. Cohort 4 d. Patients must have primary tumor location in oropharynx. Unknown primary tumors are not included. e. Primary tumor must be HPV-positive, confirmed by positive p16 test or highrisk HPV ISH in tissue (current or archival). f. Participants must provide local testing results of PD-L1 status, if available. Cohort 5: g. The eligible primary tumor location are the oropharynx, oral cavity, hypopharynx, or larynx. h. HPV status must be known (either positive or negative) for patients with primary tumor location in oropharynx with p16 test or high-risk HPV ISH in tissue. i. Participants must provide local testing results of PD-L1 status. Cohort 6: j. The eligible primary tumor locations are the oropharynx, oral cavity, hypopharynx, or larynx. k. Any known p16 status of tumor must be negative. Note: All participants with an oropharyngeal tumor must have results of p16 status, per local testing. Participants must provide local testing results of PD-L1 status. l. Participants must have Stage III or IVa disease (American Joint Committee on Cancer Staging Manual, 8th edition). Participants must have resectable disease.\n- 3. Participants must meet the following cohort-specific requirements: Cohort 3A: Dose Confirmation Cohort a. Have evaluable disease (defined as having at least 1 non-target lesion according to RECIST v1.1). If only 1 evaluable lesion exists, it may be used for the screening biopsy as long as baseline tumor assessment scans are performed ≥7 days after the biopsy. Tumor lesions situated in a previously irradiated area are considered evaluable if progression following radiation has been demonstrated in such lesions. Cohorts 1, 3B and 4: Dose Expansion Cohorts b. Have measurable disease according to RECIST v1.1. If only 1 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. Tumor lesions situated in a previously irradiated area are considered measurable if progression following radiation has been demonstrated in such lesions. A lesion that was biopsied during Screening should only be assessed as a target lesion if a post-biopsy imaging is performed >7 days and confirms that it still meets measurability criteria and is amenable to accurate and reproducible measurement. Cohorts 2 and 5: Dose Expansion Cohorts c. Have measurable disease according to RECIST v1.1. If only 1 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. Tumor lesions situated in a previously irradiated area are considered measurable if progression following radiation has been demonstrated in such lesions. Cohort 6: d. Have evaluable disease (defined as having at least 1 non-target lesion according to RECIST v1.1). If only 1 evaluable lesion exists, it may be used for the screening biopsy as long as baseline tumor assessment scans are performed ≥7 days after the biopsy.\n- 4. If available, provide adequate tumor tissue for a baseline sample following the most recent systemic anticancer therapy. The tissue sample should meet the sample requirements as outlined in the lab manual and should be accompanied with pathology report to review tumor specifications. In addition, participants must meet the following cohort-specific requirements: Cohorts 1, 3A, 3B and 4: Dose Confirmation and Expansion Cohorts a. The sponsor reserves the right to allocate the final enrollment slots in Cohorts 1 and 3B to ensure that at least 30 participants in Cohort 1 expansion (including at least 10 participants enrolled before the expansion Cohort 1 via Amendment 2), at least 10 participants in Cohorts 3A and 3B combined, and at least 10 participants in Cohort 4 provide adequate tumor tissue, either based on acceptable archival specimen or a screening biopsy. If a different dose level is used in Cohorts 3A and 3B, tumor tissue samples are required for at least 10 participants in Cohort 3B. Cohorts 2 and 5: Dose Expansion Cohorts b. If no adequate tumor tissue is available for a baseline sample, the participant must consent to a screening biopsy. If no adequate tumor tissue is available and a screening biopsy is not clinically feasible or prohibited per local regulations, the participant is not eligible. Cohort 6: c. If no adequate tumor tissue is available for a baseline sample, the participant must consent to a screening biopsy. If no adequate tumor tissue is available and a screening biopsy is not clinically feasible or prohibited per local regulations, the participant is not eligible.\n- 5. Participant may have a prior or concurrent second malignancy (other than the disease under study) which natural history or treatment is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s). Prior or concurrent second malignancies must be reviewed and agreed to with the medical monitor.\n- 6. Cohorts 1, 2, 3A, 3B, 4, and 5 only: Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less prior to the first dose of study treatment (except for alopecia or post-radiation skin changes [any grade], Grade ≤2 peripheral neuropathy and Grade ≤2 hypothyroidism stable on hormone replacement).\n- 7. Must meet the following cohort-specific requirements: (1/2) Cohort 1 and 4: Amivantamab Monotherapy a. Participant must have progressed on or after treatment for R/M disease with platinum-based chemotherapy and a PD-1/PD-L1 inhibitor (in combination or as separate lines) or have documented intolerance to these treatments. If 1 or both of these treatments were given for locally advanced disease with progression within 6 months, this may count as treatment for R/M disease. b. Participant must have progressed on most recent line for R/M disease. Maximum of 2 prior lines of systemic therapy in the R/M setting. c. Participant must have not previously received anti-EGFR therapy (inclusive of TKIs and antibodies). Cohort 2: Pembrolizumab + Amivantamab and Cohort 5: Pembrolizumab + Amivantamab + Carboplatin d. Participant must be treatment-naïve in the R/M setting. Systemic therapy which was completed more than 6 months prior to first study treatment administration, if given as part of treatment for locally advanced disease with curative intent, is allowed except for anti-EGFR or anti-PD-1/PD-L1 therapy. e. Participant must have not had disease progression within 6 months of completion of curatively intended treatment for locally advanced disease. f. Participants must have documented local testing results demonstrating a PD-L1 CPS ≥1 (using a 22C3 antibody test) within 3 months of the first dose of study treatment for Cohort 2 or within 6 months of the first dose of study treatment for Cochort 5. Local testing must be performed in accordance with local guidelines using an FDA-approved or other validated test in a CAP/CLIA certified laboratory (sites in the United States) or an accredited local laboratory (sites outside of the United States) in accordance with site SoC. In the European Union, the local test must be CE Marked or an in-house test from health institutions in the European Union in accordance with Article 5(5) of the IVDR 2071/746, as amended. Note that a copy of the test report documenting the PD-L1 must be included in the participant records.\n- 7. Must meet the following cohort-specific requirements: (2/2) Cohorts 3A and 3B: Paclitaxel + Amivantamab g. Participant must have progressed on or after treatment for R/M disease with PD-1/PD-L1 based therapy either as a monotherapy or as combination with platinum-based chemotherapy or have documented intolerance to this treatment. If this treatment was given for locally advanced disease with progression within 6 months, this may count as treatment for R/M disease. h. Participant must have progressed on most recent line for R/M disease. Maximum of 2 lines of systemic therapy in the R/M setting. i. Participant must have not previously received anti-EGFR therapy (inclusive of TKIs and antibodies) or taxane. Cohort 6: j. Participants must be treatment naïve. k. Participants must have documented local testing results demonstrating a PD-L1 CPS ≥1 (using a 22C3 antibody test) within 3 months of the first dose of study treatment. Local testing must be performed in accordance with local guidelines using an FDA-approved or other validated test in a CAP/CLIA-certified laboratory (sites in the US) or an accredited local laboratory (sites outside of the US) in accordance with site SoC. In the EU, the local test must be CE-marked or an in-house test from health institutions in the EU in accordance with Article 5(5) of the IVDR 2071/746, as amended. Note that a copy of the test report documenting the PD-L1 must be included in the participant records.\n- 8. Have an ECOG performance status of 0 to 1"}

Exclusion criteria

• {"criterion_text":"- 1. Uncontrolled illness, including but not limited to (applicable to all participants): 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. d. Impaired oxygenation requiring continuous oxygen supplementation. e. Psychiatric illness/social situation that would limit compliance with study requirements. Cohort2, Cohort 5, and Cohort 6 (ie, cohorts receiving pembrolizumab): f. Autoimmune disease that has required systemic therapy 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 therapy. g. History of Grade 3 or higher immune-related AEs from prior anticancer therapy or a monoclonal antibody, except for endocrinopathies that are stable on replacement therapies. h. Participant had an allogeneic tissue/solid organ transplant.\n- 10. Received radiotherapy for palliative purposes within 7 days of the first administration of study treatment.\n- 11. Requires a prohibited medication that cannot be discontinued, substituted, or temporarily interrupted during the study;\n- 12. Received an investigational treatment (including investigational vaccines, but not including anticancer therapy) or used an invasive investigational medical device within 6 weeks before the planned first dose of study treatment.\n- 13. Cohort 2,Cohort 5, and Cohort 6 (ie, cohorts receiving pembrolizumab): Prohibited immunosuppressive medication use within 7 days prior to the first administration of study treatment.\n- 14.Cohort 2,Cohort 5, and Cohort 6 (ie, cohorts receiving pembrolizumab): Participant has received a live or live attenuated vaccine within 30 days prior to the first dose of study drug. Vaccines approved or authorized for emergency use (eg, COVID-19) and non-live vaccines (eg, influenza) are allowed.\n- 2. Medical history of (non-infectious) ILD/pneumonitis/pulmonary fibrosis, or has current ILD/pneumonitis, or where suspected ILD/pneumonitis/pulmonary fibrosis cannot be ruled out by imaging at screening.\n- 3. Known allergies, hypersensitivity, or intolerance to excipients of amivantamab or rHuPH20 (refer to the IB). Cohort2, Cohort 5, and Cohort 6 (ie, cohorts receiving pembrolizumab):  Known allergies, hypersensitivity, intolerance, or contraindication to excipients of pembrolizumab (refer to the product label). Cohorts 3A and 3B: Paclitaxel + Amivantamab  Known allergies, hypersensitivity, intolerance, or contraindication to excipients of paclitaxel (refer to the product label). Cohort 5: Pembrolizumab + Amivantamab + Carboplatin - known allergies, hypersensitivity, intolerance, or contraindication to excipients of carboplatin (refer to the product label)\n- 4. Participant has a history of clinically significant cardiovascular disease including, but not limited to the following:  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 non-obstructive catheter-associated clots, are not exclusionary.  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).  Uncontrolled (persistent) hypertension: systolic blood pressure >180 mm Hg; diastolic blood pressure >100 mm Hg.  Congestive heart failure defined as NYHA Class III, IV or Hospitalization for congestive heart failure (any NYHA Class) within 6 months of the first dose of study treatment.  Pericarditis/clinically significant pericardial effusion.  Myocarditis.\n- 5. Participant has, or will have, any of the following: a. An invasive operative procedure with entry into a body cavity, within 4 weeks or without complete recovery before the first administration of study treatment. Thoracentesis, if needed, and percutaneous biopsy for baseline tumor tissue sample may be done less than 4 weeks prior to the first administration of study treatment, as long as the participant has adequately recovered from the procedure prior to the first dose of study treatment in the clinical judgement of the investigator. 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 Day 1). c. Expected major surgery while the investigational agent is being administered or within 6 months after the last dose of study treatment.\n- 6. Participant with untreated brain metastases\n- 7. Participant has a medical history or known presence of leptomeningeal disease, or participant has spinal cord compression not definitively treated with surgery or radiation.\n- 8. HIV-positive participants are not eligible if they meet any of the following: a. Detectable viral load (ie, >50 copies/mL) at screening. b. CD4+ count <300 cells/mm3 at screening. c. AIDS-defining opportunistic infection within 6 months of screening. d. Not receiving HAART. Any changes in HAART due to resistance/progression should occur at least 3 months prior to screening. A change in HAART due to toxicity is allowed up to 4 weeks prior to screening.\n- 9. Received prior chemotherapy, targeted cancer therapy, immunotherapy, or treatment with an investigational anticancer agent within 2 weeks or 4 half-lives, whichever is longer, before the first administration of study treatment. The maximum required washout is 28 days."}

Primary endpoints

• {"endpoint_text":"- Cohorts 1, 2, 3b and 5: ORR, according to RECIST v1.1.\n- Cohort 3A: - Incidence of DLTs - Incidence and severity of TEAEs\n- Cohort 6: - MPR","definition_or_measurement_approach":"ORR: overall response rate measured according to RECIST v1.1. DLTs: incidence of dose-limiting toxicities (as defined in protocol). TEAEs: incidence and severity of treatment-emergent adverse events. MPR: major pathological response."}

Germany

Earliest CTIS Part Ii Submission Date

19-04-2024

Latest Decision Or Authorization Date

15-01-2026

Processing Time Days

636

Number Of Sites

3

Number Of Participants

11

Poland

Earliest CTIS Part Ii Submission Date

30-04-2024

Latest Decision Or Authorization Date

19-01-2026

Processing Time Days

629

Number Of Sites

3

Number Of Participants

10

Spain

Earliest CTIS Part Ii Submission Date

23-04-2024

Latest Decision Or Authorization Date

19-01-2026

Processing Time Days

636

Number Of Sites

4

Number Of Participants

15

France

Earliest CTIS Part Ii Submission Date

27-05-2024

Latest Decision Or Authorization Date

15-01-2026

Processing Time Days

598

Number Of Sites

5

Number Of Participants

19

Primary sponsor

Full Name

Janssen Cilag International

Organisation Type

Pharmaceutical company

Country Of Registered Address

Belgium

Contract research organisations

Name

Bioclinica Inc.

Responsibilities

Medical image collect & hold

Name

Venn Life Sciences Ed B.V.

Responsibilities

PK data analysis as secondary objective in the phase 1b study

Name

Iqvia Rds Inc.

Responsibilities

Data Management PKO

Name

Almac Clinical Technologies LLC

Responsibilities

Drug supply site/closure/inventory management, subject status management, site activation

Name

Smithers PDS LLC

Responsibilities

Serum PK & ADA concentration (amivantamab)

Name

Guardant Health Inc.

Responsibilities

Histopathology- cDNA blood + blood plasma sample testing, laboratory test used at this facility is CEmarked

Name

Labcorp Central Laboratory Services LP

Responsibilities

Supply of materials required for collection and transport of PK and biomarker samples to sites; Immunogenicity (ADA, NAb) Analysis - rHuPH20

Name

Cellcarta Naperville LLC

Third parties

• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Medical image collect & hold","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Netherlands","full_name":"Venn Life Sciences Ed B.V.","duties_or_roles":"PK data analysis as secondary objective in the phase 1b study","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Cellcarta Naperville LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"Drug supply site/closure/inventory management, subject status management, site activation","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Smithers PDS LLC","duties_or_roles":"Serum PK & ADA concentration (amivantamab)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Iqvia Rds Inc.","duties_or_roles":"Data Management PKO","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Guardant Health Inc.","duties_or_roles":"Histopathology- cDNA blood + blood plasma sample testing, laboratory test used at this facility is Cemarked","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"Supply of materials required for collection and transport of PK and biomarker samples to sites; Immunogenicity (ADA, NAb) Analysis - rHuPH20","organisation_type":"Pharmaceutical company"}