Trial Title:
PD-L1 T-haNK, N-803 IL-15sa and Cetuximab for Recurrent, Metastatic HNSCC
NCT ID:
NCT06239220
Condition:
Head and Neck Cancer
Head and Neck Squamous Cell Carcinoma
Metastatic Head and Neck Cancer
Recurrent Head and Neck Cancer
Metastatic Head-and-neck Squamous-cell Carcinoma
Recurrent Head and Neck Squamous Cell Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Squamous Cell Carcinoma of Head and Neck
Recurrence
Cetuximab
Conditions: Keywords:
Head and Neck Cancer
Head and Neck Squamous Cell Carcinoma
Metastatic Head and Neck Cancer
Recurrent Head and Neck Cancer
Metastatic Head-and-neck Squamous-cell Carcinoma
Recurrent Head and Neck Squamous Cell Carcinoma
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
PD-L1 t-haNK
Description:
Allogeneic, stable, clonal natural killer cell line product, via intravenous infusion
(into the vein) per protocol.
Arm group label:
Dose Level -1: PD-L1 t-haNK + N-803 + Cetuximab
Arm group label:
Dose Level 0: PD-L1 t-haNK + N-803 + Cetuximab
Other name:
NK-92
Intervention type:
Drug
Intervention name:
Cetuximab
Description:
Epidermal growth factor receptor, via intravenous (into the vein) infusion per
institutional standard of care.
Arm group label:
Dose Level -1: PD-L1 t-haNK + N-803 + Cetuximab
Arm group label:
Dose Level 0: PD-L1 t-haNK + N-803 + Cetuximab
Other name:
Erbitux
Intervention type:
Biological
Intervention name:
N-803
Description:
Recombinant human superagonist, via subcutaneous injection (under the skin) per protocol.
Arm group label:
Dose Level -1: PD-L1 t-haNK + N-803 + Cetuximab
Arm group label:
Dose Level 0: PD-L1 t-haNK + N-803 + Cetuximab
Other name:
Interleukin-15
Other name:
IL-15
Other name:
Anktiva
Summary:
The purpose of this research study is to test the safety and efficacy of the combination
of PD-L1 t-haNK (modified immune cells), N-803 (a manufactured protein that stimulates
the immune system), and cetuximab (a targeted antibody) in treating advanced head and
neck cancer.
The names of the therapies involved in this study are:
- PD-L1 t-haNK cell therapy (a NK cell therapy infusion)
- N-803 (a type of recombinant human superagonist)
- Cetuximab (a type of antibody)
Detailed description:
This research study is to test the safety and efficacy of the combination of PD-L1 t-haNK
(modified immune cells), N-803 (a manufactured protein that stimulates the immune
system), and cetuximab (a targeted antibody) in treating advanced head and neck cancer.
PD-L1 t-haNK in combination with the immunotherapies, N-803 and cetuximab, may work
together to increase the activity and durability of the NK cells in fighting cancer
cells.
The U.S. Food and Drug Administration (FDA) has not approved PD-L1 t-haNK cells or N-803
as a treatment for advanced head and neck cancer, but the FDA has approved cetuximab as a
treatment option for advanced head and neck cancer. This trial will test these agents in
combination.
The research study procedures include screening for eligibility, study treatment visits,
Computed Tomography (CT) scans, Magnetic Resonance Imaging (MRI), Positron Emission
Tomography (PET) scans, blood tests, and electrocardiogram (ECGs).
Participants will receive study treatment every 2 weeks for at least 1 year and will be
followed for up to 15 years, as the FDA requires for any participant who has received
genetically modified cells.
It is expected that about 25 people will take part in this research study.
ImmunityBio is supplying PD-L1 t-haNK and N-803 for the study.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Participants must have an existing histologically confirmed diagnosis of head and
neck squamous cell carcinoma (HNSCC) with evidence of recurrent, metastatic (R/M) or
locoregionally advanced, incurable or unresectable disease from any mucosal subsite
including oral cavity, oropharynx, larynx, hypopharynx, nasal cavity, and the
paranasal sinuses.
- Participants must have at least one RECIST v1.1 measurable lesion, as defined as at
least one lesion that can be accurately measured in at least one dimension (longest
diameter to be recorded for non-nodal lesions and short axis for nodal lesions) ≥ 1
cm with CT scans or MR imaging.
- Must have had at least 1, but no more than 2, prior lines of prior systemic therapy
for R/M HNSCC; one of these lines should have included anti-PD-1/L1 therapy.
- a.Platinum-based therapy as part of definitive/adjuvant or curative-intent
treatment can count as 1 prior line of therapy if the subject progressed within
6 months of receiving therapy.
- b. At least 2 weeks must have elapsed since the end of prior chemotherapy,
biological agents (2 weeks for anti-cancer monoclonal antibody containing
regimens) or any investigational drug product, with adequate recovery of
treatment-related toxicity to NCI CTCAE v5 grade ≤1 (or tolerable grade 2) or
back to baseline (except for alopecia or peripheral neuropathy).
- Be ≥18 years of age on the day of signing informed consent.
- Must provide prior documentation on tumor PD-L1 expression status and HPV status
(for oropharyngeal cancer cases), if available from the medical record.
- Have a performance status of 0 or 1 on the ECOG Performance Scale (see Appendix A).
- Participants must have adequate organ and marrow function as defined below (within
14 days prior to study registration):
- a. ANC ≥1,000/mcL
- b. Hemoglobin ≥9 g/dL
- c. Platelets ≥100,000/mcL
- d. Total bilirubin ≤ upper limit of normal (ULN)
- e. AST(SGOT)/ALT(SGPT) ≤2.5x institutional ULN (or ≤1.5x institutional ULN if
concomitant with alkaline phosphatase >2.5x institutional ULN) or ≤5x ULN for
those with liver metastases
- f. Serum creatinine ≤1.5x ULN or creatinine clearance ≥60 mL/min/1.73 m2 for
participants with creatinine levels above 1.5x ULN
- Baseline tumor measurements must be documented from imaging within 28 days prior to
study registration.
- Female subjects of childbearing potential should have a negative urine or serum
pregnancy test within 7 days of study registration. Male subjects should use a
condom as a contraceptive during the study and through 6 months after the last dose
of study drugs.
Sperm donation is discouraged for up to 6 months after the last dose of study drug.
-Be willing and able to provide written informed consent for the trial.
Exclusion Criteria
- Have been previously treated with 3 or more lines of systemic therapy for R/M HNSCC.
- Have received radiation therapy (RT) within 10 days of starting protocol therapy.
- Solid organ transplant (allograft) recipients.
- Participant has known active central nervous system (CNS) metastases and/or
carcinomatous meningitis. Subjects with previously treated brain metastases may
participate provided they are stable (without evidence of progression by imaging and
off systemic steroids for at least 3 weeks prior to study registration) and have no
evidence of new or enlarging brain metastases.
- A history of significant autoimmune disease as judged by the treating investigator
and on active therapy including prednisone ≥10 mg daily dose equivalent of
corticosteroids.
- Uncontrolled intercurrent illness including but not limited to ongoing or active
infection; evidence of symptomatic congestive heart failure, unstable angina
pectoris, stroke, or ventricular arrhythmia within 6 months of enrollment.
- Has a known additional malignancy that is progressing or requires active treatment.
Exceptions might include basal cell carcinoma of the skin or squamous cell carcinoma
of the skin that has undergone potentially curative therapy or in situ cervical
cancer.
- Any known positive test result for hepatitis B virus or hepatitis C virus indicating
presence of virus, e.g., hepatitis B surface antigen (HBsAg, Australia antigen)
positive, or hepatitis C antibody (anti-HCV) positive (except if HCV-RNA negative).
Patients with HIV are eligible if their plasma HIV viral load is undetectable at
baseline on antiretroviral therapy.
- Subjects who are pregnant, or breastfeeding, or expecting to conceive or father
children within the projected duration of the trial, starting with the pre-screening
or screening visit through 120 days after the last dose of trial treatment.
Breastfeeding should be discontinued if the mother is treated on this protocol.
Women who could potentially become pregnant while undergoing treatment on this
protocol must be willing to use 2 methods of contraception.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Brigham and Women's Hospital
Address:
City:
Boston
Zip:
02115
Country:
United States
Status:
Recruiting
Contact:
Last name:
Glenn J Hanna, MD
Phone:
617-632-3779
Email:
glenn_hanna@dfci.harvard.edu
Contact backup:
Last name:
Glenn J Hanna, MD
Facility:
Name:
Dana Farber Cancer Institute
Address:
City:
Boston
Zip:
02115
Country:
United States
Status:
Recruiting
Contact:
Last name:
Glenn J Hanna, MD
Phone:
617-632-3779
Email:
glenn_hanna@dfci.harvard.edu
Contact backup:
Last name:
Glenn J Hanna, MD
Start date:
February 16, 2024
Completion date:
January 31, 2027
Lead sponsor:
Agency:
Glenn J. Hanna
Agency class:
Other
Collaborator:
Agency:
ImmunityBio, Inc.
Agency class:
Industry
Source:
Dana-Farber Cancer Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06239220
