Head and neck squamous cell carcinoma Head and Neck cancer Head and Neck squamous cell carcinoma
Conditions
Interventions
Patients will be administered ALX148 45 mg/kg Q3W in a 21-day cycle with
pembrolizumab dosed at 200 mg IV infusion over 30 minutes every 3 weeks for up
to a maximum of 35 cycles (approximately 24 mo
Sponsors
ALX Oncology Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Patients with metastatic or unresectable, recurrent head and neck squamous cell carcinoma (HNSCC) who have not received prior systemic therapy for their advanced disease. PD-L1 status as defined by combined positive score (CPS) and as assessed by an FDA-approved test using the 22C3 antibody must be available. • Patients cannot have received prior systemic therapy for the treatment of metastatic or recurrent disease. • Patients can have received prior systemic therapy for the treatment of locoregionally advanced disease if it was completed more than 6 months prior to signing informed consent. 2. Patients must have at least one measurable lesion as defined by RECIST version 1.1. 3. Adequate bone marrow function. 4. Adequate renal function (estimated creatinine clearance by Cockroft-Gault equation of >= 60 mL/min.). 5. Adequate liver function. 6. Age >=18 years, except in regions in which the minimum age for subject participation is >18 years. 7. INR or PT and PTT
Exclusion criteria
Exclusion criteria: 1. Patients with disease suitable for local therapy with curative intent. 2. Patients with progressive disease within 6 months of completion of curatively intended systemic therapy for the treatment of locoregionally advanced HNSCC. 3. Patients with nasopharyngeal carcinoma (NPC). 4. Patients with known symptomatic CNS metastases requiring steroids or with leptomeningeal disease. 5. Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease. 6. Prior radiotherapy within 2 weeks of start of study treatment. 7. Prior treatment with any anti-CD47 or anti-SIRPa agent. 8. Prior treatment with a PD-1 or PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T cell receptor (e.g., CTLA-4, OX 40, CD137). 9. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug. 10. Has a diagnosis of complete dihydropyrimidine dehydrogenase (DPD) deficiency. Testing for DPD status is required for sites/regions in which such testing is standard of care (such as in the United Kingdom). 11. Has an active autoimmune disease that has required systemic treatment in past 2 years. 12. History of autoimmune hemolytic anemia, autoimmune thrombocytopenia, or hemolytic transfusion reaction. 13. Patients with intolerance to or who have had a severe allergic or anaphylactic reaction to antibodies or infused therapeutic proteins or patients who have had a severe allergic or anaphylactic reaction to any of the substances included in the study drugs. 14. Patients with significant hearing impairment. 15. Any experimental antibodies or live vaccines in the last 30 days prior to the first dose of study drug. 16. Patients with active, uncontrolled, clinically significant bacterial, fungal, or viral infection. 17. Has an active infection requiring systemic therapy. 18. Has had an allogeneic tissue/solid organ transplant. 19. Any of the following in the previous 6 months: myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, NYHA Class II or greater congestive heart failure, cerebrovascular accident, or transient ischemic attack, deep venous thrombosis, arterial thrombosis, symptomatic pulmonary embolism, or any other significant thromboembolism. Any major surgery within 28 days prior to enrollment. 20. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. 21. Diagnosis of any other malignancy within the last 3 years prior to enrollment except for adequately treated non-melanomatous skin cancer, or carcinoma in situ that have undergone potentially curative therapy. 22. Other severe acute or chronic medical or psychiatric condition. 23. Patients who are pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Endpoint • 12-month overall survival (OS) rate of ALX148 + pembrolizumab + 5FU + platinum. • Objective response rate of ALX148 + pembrolizumab + 5FU + platinum (ORR; CR or PR using the Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoints • Disease control rate (DCR), duration of response (DOR), time to tumor progression (TTP). • Progression-free survival (PFS), and overall survival (OS). • Adverse Events as characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v. 5.0), timing, seriousness, and relationship to study therapy. • Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v. 5.0) and timing. • Pharmacokinetic parameters of ALX148 such as Cmax, Tmax, AUC, CL, and t1/2 as data permit. • Immunogenicity; Human serum ADA (i.e., anti-ALX148 antibody) samples will be analyzed for the presence or absence of anti-ALX148 antibodies. | — |
Countries
Netherlands
Outcome results
None listed