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

Phase 2

• Conditions: Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma; Cancer

• Registration Number: ISRCTN98745687
• Lead Sponsor: Janssen-Cilag International NV

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-03-12
• Last Update Posted: 27 May 2024
• Study Completion: 2026-07-17

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 117

Inclusion Criteria

1. Be at least 18 years of age at the time of informed consent.
2. Have histologically or cytologically confirmed recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) that is considered incurable by local therapies.
3. Participants must meet the following cohort-specific requirements:
Cohort 3A: Dose Confirmation Cohort: 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 tumour assessment scans are performed 7 or more days after the biopsy. Tumour lesions situated in a previously irradiated area are considered evaluable if progression following radiation has been demonstrated in such lesions.
Cohorts 1, 2, and 3B: Dose Expansion Cohorts: 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 tumour assessment scans are performed 7 or more days after the biopsy. Tumour lesions situated in a previously irradiated area are considered measurable if progression following radiation has been demonstrated in such lesions.
4. If available, provide adequate tumour tissue for a baseline sample following the most recent systemic anticancer therapy.
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.
6. 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 lower than or equal to 2 peripheral neuropathy and Grade lower than or equal to 2 hypothyroidism stable on hormone replacement).
7. Must meet the protocol defined cohort-specific requirements (See protocol for full details).
8. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
9. Have at least 1 of the following:
a. Serum creatinine lower than or equal to 1.5 x upper limit of normal (ULN).
b. Estimated glomerular filtration rate greater than or equal to 45 millilitre per minute, based on the Modified Diet in Renal Disease (MDRD) 4-variable formula.
10. Participants are eligible if they have the following lab values:
a. Aspartate aminotransferase (AST) lower than or equal to 3 x ULN (lower than or equal to 5 x ULN if liver metastases are present)
b. ALT lower than or equal to 3 x ULN (lower than or equal to 5 x ULN if liver metastases are present)
c. Total bilirubin lower than or equal to 1.5 x ULN; participants with congenital nonhemolytic hyperbilirubinemia such as Gilbert’s syndrome can enroll if conjugated bilirubin is within normal limits.
11. Participant must have adequate organ and bone marrow function as per protocol criteria, 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.
12. Cohort 2: Thyroid function laboratory values within the normal range.
13. While on study treatment and for 10 months after the last dose of study treatment, a
participant must:
- Not breastfeed or be pregnant.
- Not donate gametes (i.e., eggs or sperm) or freeze for f

Exclusion Criteria

1. Uncontrolled illness, including but not limited to all conditions specified in the protocol.
2. Medical history of (non-infectious) interstitial lung disease (ILD)/pneumonitis/pulmonary fibrosis, or has current ILD/pneumonitis, or suspected ILD/pneumonitis/pulmonary fibrosis cannot be ruled out by imaging at screening.
3. Known allergies, hypersensitivity, or intolerance to excipients of amivantamab, recombinant human hyaluronidase (rHuPH20), or other study treatment.
4. Participant has a history of clinically significant cardiovascular disease, as specified in the study protocol.
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.
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.
6. Participant with untreated brain metastases
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.
8. HIV-positive participants are not eligible if they meet any of protocol specified criteria.
9. Active hepatitis of infectious origin.
10. 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.
11. Received radiotherapy for palliative purposes within 7 days of the first administration of study treatment.
12. Requires a prohibited medication that cannot be discontinued, substituted, or temporarily interrupted during the study.
13. 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.
14. Cohort 2: Prohibited immunosuppressive medication use within 7 days prior to the first administration of study treatment.
15. Cohort 2: Participant has received a live or live attenuated vaccine within 30 days prior to the first dose of study drug. Vaccines approved or authorised for emergency use and non-live vaccines are allowed.
16. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.

Study & Design

• Study Type: Interventional
• Study Design: Not specified