A PHASE 2 STUDY OF ALX148 IN COMBINATION WITH PEMBROLIZUMAB AND CHEMOTHERAPY IN PATIENTS WITH ADVANCED HEAD AND NECK SQUAMOUS CELL CARCINOMA (ASPEN-04)
- Conditions
- Head and neck squamous cell carcinomaHead and Neck cancerHead and Neck squamous cell carcinoma
- Registration Number
- NL-OMON54403
- Lead Sponsor
- ALX Oncology Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 7
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 <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. ECOG performance status
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. Participants
with <=Grade 2 neuropathy may be eligible. 11. Available core or incisional
biopsy sample prior to study entry, preferably taken after the most recent
therapy for HNSCC, for central confirmation of PD-L1 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 and at least 6 months (or longer
if required by local regulation) after the last dose of chemotherapy, whichever
is later. 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 study before any study-specific
activity is performed. 15. Patients who are willing and able to comply with
scheduled visits, treatment plans, laboratory tests, and other procedures.
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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Endpoint<br /><br>• 12-month overall survival (OS) rate of ALX148 + pembrolizumab + 5FU +<br /><br>platinum.<br /><br>• Objective response rate of ALX148 + pembrolizumab + 5FU + platinum (ORR; CR<br /><br>or PR using the Response Evaluation Criteria in Solid Tumors<br /><br>[RECIST] version 1.1).</p><br>
- Secondary Outcome Measures
Name Time Method <p> Secondary Endpoints<br /><br>• Disease control rate (DCR), duration of response (DOR), time to tumor<br /><br>progression (TTP).<br /><br>• Progression-free survival (PFS), and overall survival (OS).<br /><br>• Adverse Events as characterized by type, frequency, severity (as graded by<br /><br>National Cancer Institute Common Terminology Criteria for<br /><br>Adverse Events (NCI CTCAE v. 5.0), timing, seriousness, and relationship to<br /><br>study therapy.<br /><br>• Laboratory abnormalities as characterized by type, frequency, severity (as<br /><br>graded by NCI CTCAE v. 5.0) and timing.<br /><br>• Pharmacokinetic parameters of ALX148 such as Cmax, Tmax, AUC, CL, and t1/2 as<br /><br>data permit.<br /><br>• Immunogenicity; Human serum ADA (i.e., anti-ALX148 antibody) samples will be<br /><br>analyzed for the presence or absence of anti-ALX148<br /><br>antibodies.</p><br>