A PHASE 2 STUDY OF ALX148 IN COMBINATION WITH PEMBROLIZUMAB IN PATIENTS WITH ADVANCED HEAD AND NECK SQUAMOUS CELL CARCINOMA (ASPEN-03)
- Conditions
- Head and Neck squamous cell carcinomaHead and Neck cancer
- Registration Number
- NL-OMON56262
- Lead Sponsor
- ALX Oncology Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 11
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 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, 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. 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 conse
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. 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).
9. 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 IB 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 infect
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 plus pembrolizumab.<br /><br>• Objective response rate of ALX148 plus pembrolizumab (ORR; CR or PR using the<br /><br>Response Evaluation Criteria in Solid Tumors [RECIST]<br /><br>version 1.1).</p><br>
- Secondary Outcome Measures
Name Time Method <p>• 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>