A trial in patients with advanced head and neck cancer looking at combining ALX148 and pembrolizumab

Phase 1

• Conditions: Patients with metastatic or unresectable, recurrent HNSCC who have not yet been treated for their advanced disease; MedDRA version: 20.0Level: LLTClassification code 10007050Term: CancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: PTClassification code 10041823Term: Squamous cell carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10007284Term: CarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: PTClassification code 10060121Term: Squamous cell carcinoma of head and neckSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10067821Term: Head and neck cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 22.0Level: LLTClassification code 10082179Term: Squamous cell carcinoma of head and neck metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-004093-21-BE
• Lead Sponsor: ALX Oncology Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-05-26
• Last Update Posted: 13 May 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 177

Inclusion Criteria

1. 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.
2. 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.
3. 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)
4. Adequate renal function (obtained within 10 days of first planned dose), including:
a. Estimated creatinine clearance (using Cockroft-Gault equation) = 30 mL/min.
5. Adequate liver function (obtained within 10 days of first planned dose), including:
a. Total serum 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
6. Age =18 years, except in regions in which the minimum age for subject participation is >18 years.
7. 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.
8. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) must be 0 or 1.
9. Participants with oropharyngeal carcinoma must have available results from testing of human papillomavirus (HPV) (p16) status.
10. 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.
11. Available core or incisional biopsy sample prior to study entry that has been taken after the most recent therapy for HNSCC taken from either an unresectable recurrent lesion or a metastatic lesion for central confirmation of CPS and evaluation of other biomarkers. Fine needle aspirates are not acceptable.
12. Serum pregnancy test (for females of childbearing potential) negative at screening.
13. 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.
14. 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 stud

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 or leptomeningeal disease requiring steroids. 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 metastases and are clinically stable off anticonvulsants for at least 4 weeks and are neurologically stable before enrollment.
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. Note: Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (defined as =2 weeks of radiotherapy) to non-CNS disease.
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).
09. Has a diagnosis of immunodeficiency (with the exception of hypogammaglobulinemia) or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
10. 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.
11. History of autoimmune hemolytic anemia, autoimmune thrombocytopenia, or hemolytic transfusion reaction.
12. 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 (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”).
13. 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.
14. 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.
15. Has an active infection requiring systemi

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified