A Phase 2 study of ALX148 in Combination With Pembrolizumab and Chemotherapy in Patients with Advanced Head and Neck Squamous Cell Carcinoma (ASPEN-04)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Alx Oncology Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

11 Aug 2021 → 15 Apr 2026

Decision date (initial)

2024-05-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

ALX Oncology Inc.

External identifiers

EU CT number

2023-508342-17-00

EudraCT number

2020-004662-19

ClinicalTrials.gov

NCT04675333

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy, Dose response, Therapy, Others, Pharmacodynamic, Pharmacogenomic

To assess the effect of ALX148 + pembrolizumab + 5FU + platinum (carboplatin or cisplatin) on 12-month overall survival (OS) rate and objective response rate (ORR) in patients with metastatic or unresectable, recurrent HNSCC who have not yet been treated for their advanced disease.

Secondary objectives 2

1. To assess secondary measures of efficacy for ALX148 administered in combination with pembrolizumab + 5FU + platinum and for pembrolizumab + 5FU + platinum.
2. To assess the safety and tolerability of ALX148 administered in combination with pembrolizumab + 5FU + platinum and for pembrolizumab + 5FU + platinum (including for patients in the safety lead-in cohort).

Conditions and MedDRA coding

metastatic or unresectable, recurrent HNSCC

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

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. 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 21 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) - criteria 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 21 days of first planned dose), including: a. Estimated creatinine clearance (using Cockroft-Gault equation) ≥ 60 mL/min. b. Adequate renal function to support administration of platinum therapy.
5. Adequate liver function (obtained within 21 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).
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. 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 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.

Exclusion criteria 21

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 (≤2 weeks of radiotherapy) to non-CNS disease.
7. Prior treatment with any anti-CD47 or anti-SIRPα 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 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.
11. 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.
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 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").
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. 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.
16. 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.
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. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
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 (e.g., breast carcinoma in situ, cervical cancer in situ, prostate carcinoma in situ) that have undergone potentially curative therapy.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 endpoints 6

1. Disease control rate (DCR), duration of response (DOR), time to tumor progression (TTP).
2. Progression-free survival (PFS), and overall survival (OS).
3. 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.
4. Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v. 5.0) and timing.
5. Pharmacokinetic parameters of ALX148 such as Cmax, Tmax, AUC, CL, and t1/2 as data permit.
6. Immunogenicity; Human serum ADA (i.e., anti-ALX148 antibody) samples will be analyzed for the presence or absence of anti-ALX148 antibodies.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Alx Oncology Inc.

Sponsor organisation

Alx Oncology Inc.

Address

323 Allerton Avenue

City

South San Francisco

Postcode

94080-4816

Country

United States

Scientific contact point

Organisation

Alx Oncology Inc.

Contact name

Sr. VP of Clinical Development

Public contact point

Organisation

Alx Oncology Inc.

Contact name

Sr. VP of Clinical Development

Third parties 5

Locations

3 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 27 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications