A Phase 2 Study of ALX148 in Combination with Pembrolizumab in Patients with Advanced Head and Neck Squamous Cell Carcinoma (ASPEN-03)
- Conditions
- metastatic or unresectable, recurrent HNSCCMedDRA version: 26.1Level: PTClassification code: 10060121Term: Squamous cell carcinoma of head and neck Class: 100000004864MedDRA version: 21.1Level: PTClassification code: 10067821Term: Head and neck cancer Class: 100000004864MedDRA version: 21.0Level: PTClassification code: 10041823Term: Squamous cell carcinoma Class: 100000004864MedDRA version: 22.0Level: LLTClassification code: 10082179Term: Squamous cell carcinoma of head and neck metastatic Class: 10029104MedDRA version: 20.0Level: LLTClassification code: 10007284Term: Carcinoma Class: 10029104MedDRA version: 20.0Level: LLTClassification code: 10007050Term: Cancer Class: 10029104Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-508340-22-00
- Lead Sponsor
- Alx Oncology Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 177
Patients with metastatic or unresectable, recurrent head and neck squamous cell carcinoma (HNSCC) that is PD-L1 positive (defined as CPS > 1 by an FDA-approved test utilizing the 22C3 antibody and by any required locally approved test) and who have not received prior systemic therapy for their advanced disease. • 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., Participants must have recovered from all AEs due to previous therapies, procedures, and surgeries to baseline or =Grade 1 per NCI CTCAE v. 5.0 except for AEs not constituting a safety risk by Investigator judgment (e.g. alopecia). Participants with =Grade 2 neuropathy may be eligible., Available core or incisional biopsy sample prior to study entry preferably taken after the most recent therapy for HNSCC for central confirmation of CPS and evaluation of other biomarkers. Fine needle aspirates are not acceptable., Serum pregnancy test (for females of childbearing potential) negative at screening., Male and female patients of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 120 days after the last dose of assigned treatment. A patient is of childbearing potential if, in the opinion of the Investigator, he/she is biologically capable of having children and is sexually active., Evidence of a personally signed and dated informed consent document, from a patient with the capacity to consent for themselves or from a legal representative, indicating that the patient or legal representative has been informed of all pertinent aspects of the study before any study-specific activity is performed., Patients who are willing and able to comply with scheduled visits, treatment plans, laboratory tests and other procedures., Patients must have at least one measurable lesion as defined by RECIST version 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions., Adequate bone marrow function (obtained within 10 days of first planned dose), including: a. Absolute Neutrophil Count (ANC) =1,500/mm3 (=1.5 x 109/L); b. Platelets =100,000/mm3 (=100 x 109/L); c. Hemoglobin =9 g/dL (=90 g/L) - must be met without packed red blood cell (pRBC) transfusion within the prior 2 weeks. Participants can be on stable doses of erythropoietin (= approximately 3 months), Adequate renal function (obtained within 10 days of first planned dose), including: a. Estimated creatinine clearance (using Cockroft-Gault equation) = 30 mL/min., Adequate liver function (obtained within 10 days of first planned dose), including: a. Total bilirubin =1.5 x ULN (=3.0 x ULN if the patient has documented Gilbert syndrome); b. Aspartate and Alanine transaminase (AST and ALT) =2.5 x ULN; =5.0 x ULN if there is liver involvement secondary to tumor, Age =18 years, except in regions in which the minimum age for subject participation is >18 years., INR or PT and PTT <1.5X ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants., Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) must be 0 or 1., Participants with oropharyngeal carcinoma must have available results
Patients with disease suitable for local therapy with curative intent, Has an active autoimmune disease that has required systemic treatment in past 2 years (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) is not considered a form of systemic treatment and is allowed., History of autoimmune hemolytic anemia, autoimmune thrombocytopenia, or hemolytic transfusion reaction., 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 drug (including but not limited to excipients, which are listed in the ALX148 Investigator's Brochure in Section 4.4 Formulation of the Dosage Form to be Used)., Any experimental antibodies or live vaccines in the last 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed., Patients with active, uncontrolled, clinically significant bacterial, fungal, or viral infection, including hepatitis B (HBV), hepatitis C (HCV), known infection with SARS-CoV-2, known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)related illness., Has an active infection requiring systemic therapy., Has had an allogeneic tissue/solid organ transplant., 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., 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. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been at least 4 weeks after the last dose of the previous investigational agent, 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 (e.g., breast carcinoma in situ, cervical cancer in situ, prostate carcinoma in situ) that have undergone potentially curative therapy, Patients with progressive disease within 6 months of completion of curatively intended systemic therapy for the treatment of locoregionally advanced HNSCC., Patients with nasopharyngeal carcinoma (NPC)., Patients with known symptomatic CNS metastases requiring steroids or with leptomeningeal disease. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for these met
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the effect of ALX148 plus pembrolizumab on 12-month overall survival (OS) rate and objective response rate (ORR) in patients with metastatic or with unresectable, recurrent HNSCC that is CPS =1 and who have not yet been treated for their advanced disease.;Secondary Objective: To assess secondary measures of efficacy for ALX148 administered in combination with pembrolizumab and for pembrolizumab alone., To assess the safety and tolerability of ALX148 administered in combination with pembrolizumab and for pembrolizumab alone (including for patients in the safety lead-in cohort).;Primary end point(s): 12-month overall survival (OS) rate of ALX148 plus pembrolizumab., Objective response rate of ALX148 plus pembrolizumab (ORR; CR or PR using the Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1).
- Secondary Outcome Measures
Name Time Method Secondary end point(s):Disease control rate (DCR), duration of response (DOR), time to tumor progression (TTP);Secondary end point(s):Progression-free survival (PFS), and overall survival (OS);Secondary end point(s):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;Secondary end point(s):Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v. 5.0) and timing;Secondary end point(s):Pharmacokinetic parameters of ALX148 such as Cmax, Tmax, AUC, CL, and t1/2 as data permit;Secondary end point(s):Immunogenicity; Human serum ADA (i.e., anti-ALX148 antibody) samples will be analyzed for the presence or absence of anti-ALX148 antibodies