FIH study of ALE.C04 anti-CLDN1 mAb monotherapy or in combination with pembrolizumab in patients with R/M HNSCC
- Conditions
- Recurrent or Metastatic (R/M) Head and Neck Squamous Cell CarcinomaMedDRA version: 21.0Level: PTClassification code: 10060121Term: Squamous cell carcinoma of head and neck Class: 100000004864Therapeutic area: Diseases [C] - Neoplasms [C04]MedDRA version: 22.0Level: LLTClassification code: 10082179Term: Squamous cell carcinoma of head and neck metastatic Class: 10029104
- Registration Number
- CTIS2023-505145-93-00
- Lead Sponsor
- Alentis Therapeutics AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 220
Be willing and able to provide written informed consents (Pre-Screening informed consent will be considered in addition to main informed consent) for the clinical study. The patient may also provide consent for Future Biomedical Research. However, the patient may participate in the main clinical study without participating in Future Biomedical Research., Female patients of childbearing potential should not be breastfeeding and should be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity and must agree not to donate eggs (ova, oocytes) for the purpose of reproduction for the course of the study through 90 days or 5 half-lives whichever is longer after the last dose of ALE.C04 study medication or 4 months after the last dose of pembrolizumab when applicable. Patients of childbearing potential are those who have not been surgically sterilized or have not been free from menses for >1 year. Note: Non-child-bearing potential is defined by fulfilling one of the following criteria at screening: i.Post-menopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments (where applicable). The levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) must also be in the post-menopausal range (for the institution). ii. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation., Male patients should agree to use an adequate method of contraception and to abstain from sperm donation starting with the first dose of study therapy through 90 days or 5 half-lives whichever is longer after the last dose of ALE.C04 study medication or 4 month after the last dose of pembrolizumab when applicable. Note: Abstinence is acceptable if this is the usual lifestyle and preferred method of contraception for the patient., Patients should have the ability and willingness to comply with the study and follow-up., Be at least 18 years of age on day of signing informed consent., Have histologically or cytologically confirmed R/M HNSCC that is considered incurable by local therapies. a) Phase I and Phase II monotherapy: patients with documented disease progression to at least one prior line of systemic palliative treatment including a PD-1 monoclonal antibody as a single agent or in combination will be enrolled. i) The eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, larynx, nasopharynx, and HPV-positive cancer of unknown primary site that is localized to the head and neck b) Phase II (randomized): Patients should not have had prior systemic palliative treatment administered in the recurrent or metastatic setting. Systemic therapy which was completed more than 6 months prior to signing consent if given as part of multimodal treatment for locally advanced disease is allowed. i) The eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx., Have provided tissue for CLDN1, PD-L1 and biomarker analysis in a central Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory. The newly obtained tumor tissue is mandatory at baseline (i.e. within 180 days prior to start of study treatment) but an archival sample is acceptable if biopsy procedure is deemed unsafe by PI; a biopsy on treatment is mandatory in dose escalation but optional in RDEs and Phase II. Repeat samples may be
Has progressive disease (PD) within 6 months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC (Phase II randomized only)., Active autoimmune disease including Graves’ disease that has required systemic treatment (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is allowed., Has had an allogeneic tissue/solid organ transplant., Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis., Has an active infection requiring systemic treatment (e.g., intravenous or prolonged oral antibiotic treatment over 7 days)., Dermatological conditions requiring active pharmacological treatment including psoriasis, atopic dermatitis, excessively dry skin or recurrent conjunctivitis, scleroderma, vitiligo, or any other active autoimmune dermatological disorder, Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the clinical study, interfere with the patient’s participation for the full duration of the clinical study, or is not in the best interest of the patient to participate, in the opinion of the treating investigator., Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the clinical study, starting with the screening visit through 90 days or 5 half-lives whichever is longer after the last dose of ALE.C04 study medication or 4 months after the last dose of pembrolizumab when applicable., Has received prior therapy with an anti-PD-1, anti-PD-L1 or anti-PD-L2 (Phase II randomized only)., Untreated chronic hepatitis B or chronic HBV carriers with HBV DNA = 500 IU/ML (or = 2500 copies/mL) at screening. Note: Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B (HBV DBA < 500 IU/mL or < 2500 copies/mL) can be enrolled. Patients with detectable hepatitis B surface antigen (HbsAg) or detectable HFB DNA should be managed per institutional treatment guidelines., Patients with active hepatitis C. Note: Patients with a negative HCV antibody test at screening or positive HCV antibody test followed by a negative HCV RNA test at screening are eligible., Has had radiation therapy (or other non-systemic therapy) within 2 weeks prior to randomization or patient has not fully recovered (i.e., =Grade 1 or at baseline) from adverse events due to a previously administered treatment. Palliative radiotherapy to a limited field is allowed. Note: Patients with =Grade 2 neuropathy, =Grade 2 alopecia, or laboratory values as defined in the Protocol are an exception to this criterion and may qualify for the study. Note: If patients received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy., Untreated HIV infection, if known. Patients with known HIV infection are eligible if the following criteria are met: a) Stable on antiretroviral therapy for = 4 weeks before first dose of study drug b) Patient agrees to adhere to antiretroviral therapy per WHO guidelines c) No documented multidrug resistance that would prevent effective antiretroviral therapy d) Viral load of < 400 copies per mL at screening e) CD4+ T-cell count = 350 cells per µL at screenin
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method