Inclusion Criteria:
- - Have HLA-A*0201 genotype as determined by genomic testing performed locally;
- Have histologically confirmed World Health Organization (WHO) Grade 4 glioblastoma,
other WHO grade 4 malignant glioma or molecular GBM (based on the 2021 WHO
Classification) at first recurrence.
Patients with gliosarcoma are NOT eligible;
- - Be willing and able to provide written informed consent/assent for the trial;
- Be ≥ 18 years of age on day of signing informed consent;
- Have a Karnofsky performance status (KPS) ≥ 70 (Appendix A);
- Participants must be at least 4 weeks from start of last chemotherapy cycle (at
least 6 weeks for nitrosoureas and at least 1 week for metronomic dosing) and at
least 4 weeks or 5 half-lives (whichever is shorter) for any prior investigational
agent.
There is no minimal time from cessation of Optune TTF nor for prior cancer
vaccine therapy.
- - MRI within 14 days prior to registration.
MRIs should include vascular imaging when
possible. Corticosteroid dose must be stable or decreasing for at least 5 days prior
to the scan. If steroids are added or the steroid dose is increased between the date
of the screening MRI scan and the start of treatment, a new baseline MRI or CT is
required;
- - Patients must have fully completed initial radiation therapy with or without daily
temozolomide including 60 Gy in 30 fractions, 59.4 Gy in 1.8 Gy per fraction or
equivalent;
- At least 12 weeks from completion of radiotherapy +/- temozolomide.
Patients < 12
weeks from the completion of radiation therapy may be eligible if they have either
of the following: 1) histopathologic confirmation of recurrent tumor; or 2) new
contrast enhancing disease outside the primary radiation field. Participants who
have received investigational therapies as a component of treatment for newly
diagnosed GBM as long as remaining eligibility criteria are satisfied;
- - Participants must have recovered to grade 0 or 1 or pre-treatment baseline from
clinically significant toxic effects of prior therapy (exceptions include alopecia,
laboratory values listed per inclusion criteria, and lymphopenia, which is common
after therapy with temozolomide);
- Participants must meet the following organ and marrow function as defined below, all
screening labs should be performed within 14 days of registration:
- Absolute neutrophil count (ANC) ≥1,500 /mcL.
- - Platelets ≥100,000 / mcL.
- - Hemoglobin ≥9 g/dL or ≥5.6 mmol/L (Criteria must be met without erythropoietin
dependency and without packed red blood cell (pRBC) transfusion within last 2
weeks)
- Serum creatinine ≤ 1.5 X institutional ULN OR.
- - Measured or calculated creatinine clearance (CrCl) ≥45 mL/min for participant
with creatinine levels > 1.5 X institutional ULN (CrCl should be calculated per
institutional standard, GFR can also be used in place of creatinine or CrCl)
- Serum total bilirubin ≤ 1.5 X institutional ULN OR.
- - Direct bilirubin ≤ institutional ULN for participants with total bilirubin
levels > 1.5 X institutional ULN.
- - AST (SGOT) and ALT (SGPT) ≤ 3.0 X institutional ULN OR ≤ 5 X institutional ULN
for participants with Gilberts syndrome.
- - International Normalized Ratio (INR) OR Prothrombin Time (PT) and Activated
Partial Thromboplastin Time (aPTT) ≤1.5 X institutional ULN unless participant
is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic
range of intended use of anticoagulants.
- - Resting baseline oxygen saturation by pulse oximetry ≥92% at rest.
- - Women of child-bearing potential (WOCBP), defined as all women physiologically
capable of becoming pregnant, must have a negative urine or serum pregnancy within
72 hours prior to enrollment.
If the urine test is positive or cannot be confirmed
as negative, a serum pregnancy test will be required;
--Women in the following categories are not considered WOCBP:
- - Premenopausal female with 1 of the following:
- Documented hysterectomy.
- - Documented bilateral salpingectomy.
- - Documented bilateral oophorectomy.
- - Note: Documentation can come from the site personnel's review of the
participant's medical records, medical examination, or medical history
interview.
- - A postmenopausal state is defined as no menses for 12 months without an
alternative medical cause.
-----A high follicle stimulating hormone (FSH) level in the postmenopausal
range may be used to confirm a postmenopausal state in women not using
hormonal contraception or hormonal replacement therapy (HRT). However, in
the absence of 12 months of amenorrhea, confirmation with two FSH
measurements in the postmenopausal range is required.
- - Females on HRT and whose menopausal status is in doubt will be required to
use one of the non-hormonal highly effective contraception methods if they
wish to continue their HRT during the study.
Otherwise, they must
discontinue HRT to allow confirmation of postmenopausal status before
study enrollment.
- - Women of child-bearing potential (WOCBP; see definition above), must agree to use a
highly effective method of contraception consistently and correctly as described
below during study treatment and for 120 days after study treatment discontinuation
or the initiation of other cancer therapy (whichever is shorter);
- Highly Effective Contraceptive Methods That Are User Dependent a (Failure rate
of < 1% per year when used consistently and correctly.
)
- - Combined (estrogen- and progestogen- containing) hormonal contraception.
Oral.
Intravaginal.
Transdermal.
Injectable.
- - Progestogen-only hormonal contraception.
Oral.
Injectable.
- - Highly Effective Methods That Have Low User Dependency (Failure rate of <1% per
year when used consistently and correctly)
- Progestogen- only contraceptive implant.
- - Intrauterine hormone-releasing system (IUS) Intrauterine device (IUD)
- Bilateral tubal occlusion.
- - Vasectomized partner (A vasectomized partner is a highly effective
contraception method provided that the partner is the sole male sexual
partner of the WOCBP and the absence of sperm has been confirmed.
If not,
an additional highly effective method of contraception should be used).
- - Sexual abstinence (Sexual abstinence is considered a highly effective
method only if defined as refraining from heterosexual intercourse during
the entire period of risk associated with the study treatment.
The
reliability of sexual abstinence needs to be evaluated in relation to the
duration of the study and the preferred and usual lifestyle of the
participant).
- - NOTES: Use should be consistent with local regulations regarding the use
of contraceptive methods for participants of clinical studies.
Typical use failure rates are lower than perfect-use failure rates
(i.e. when used consistently and correctly).
If hormonal contraception efficacy is potentially decreased due to
interaction with study treatment, condoms must be used in addition to
the hormonal contraception during the treatment period and for at
least during study treatment and for 120 days after study treatment
discontinuation after the last dose of study treatment or the
initiation of other cancer therapy (whichever is shorter).
If locally required, in accordance with Clinical Trial
Facilitation Group (CTFG) guidelines, acceptable contraceptive
implants are limited to those which inhibit ovulation.
- - Male participants must agree to use at least one of the following methods of
contraception starting with the first dose of study therapy through 120 days after
the last dose of therapy or the initiation of other cancer therapy (whichever is
shorter):
- Be abstinent from penile-vaginal intercourse as their usual and preferred
lifestyle (abstinent on a long term and persistent basis) and agree to remain
abstinent.
- - Use a male condom plus partner use of a contraceptive method with a failure
rate of <1% per year when having penile-vaginal intercourse with a woman of
childbearing potential who is not currently pregnant.
Note: Men with a pregnant or breastfeeding partner must agree to remain
abstinent from penile-vaginal intercourse or use a male condom during each
episode of penile penetration.
Exclusion Criteria:
- - Received any therapy for tumor recurrence other than surgery;
- More than one episode of recurrent or progressive tumor;
- Is currently participating or plans to participate in another study of an
investigational agent or using an investigational device.
- - Tumor primarily localized to the brainstem or spinal cord;
- Presence of multifocal tumor, bi-hemispheric tumor (radiographic evidence of tumor
extending from one hemisphere into the other through the corpus callosum), diffuse
leptomeningeal or extracranial disease;
- Has a diagnosis of immunodeficiency;
- Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the trial, interfere with the
participant's participation for the full duration of the trial, or is not in the
best interest of the participant to participate, in the opinion of the treating
investigator.
Examples include
- - but are not limited to - unstable angina pectoris,
cardiac arrhythmia or psychiatric illness/social situations that would limit
compliance with study requirements;
- Has history of known coagulopathy that increases risk of bleeding or a history of
clinically significant hemorrhage within 12 months of enrollment;
- Has evidence of intratumoral or peritumoral hemorrhage on baseline MRI scan other
than those that are grade ≤ 1 and either post-operative or stable on at least 2
consecutive MRI scans;
- Has gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE Grade > 3
within 6 months of enrollment;
- Has a known additional malignancy that is progressing or requires active treatment
within 1 year of start of study drug, except for those treated with surgical therapy
only (e.g. basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or
in situ cervical cancer that has undergone potentially curative therapy);
- Has active autoimmune disease requiring systemic treatment in the past 2 years (i.e.
with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
Replacement therapy (eg thyroxine, insulin, or physiologic corticosteroid
replacement for adrenal insufficiency or pituitary/hypothalamic dysfunction, etc.)
is not considered a form of systemic treatment;
- - Has history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis;
- Has an active infection requiring systemic therapy within 7 days before enrollment;
- Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial;
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies) and
is receiving antiretroviral therapy.
- - Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected);
- Has a history of non-healing wounds or ulcers, or bone refractures within 3 months
of fracture;
- Has a history of arterial thromboembolism within 12 months of enrollment;
- Has had clinically significant cardiovascular disease within 12 months of start of
study drug, including myocardial infarction, unstable angina, grade 2 or greater
peripheral vascular disease, cerebrovascular accident, transient ischemic attack,
congestive heart failure, or arrhythmias not controlled by outpatient medication,
percutaneous transluminal coronary angioplasty/stent;
- Has a known history of active TB (Bacillus Tuberculosis);
- Has a known hypersensitivity to any of the study therapy products and/or any of
their excipients;
- Is pregnant or breastfeeding or expecting to conceive within the projected duration
of the trial, starting with the screening visit through 120 days after the last dose
of trial treatment or the initiation of other cancer therapy (whichever is shorter).
Pregnant women are excluded because there is an unknown but potential risk for
adverse events affecting a developing fetus and/or the mother secondary to treatment
with CUE-102. There is also an unknown but potential risk for adverse events
affecting nursing infants secondary to treatment of the mother with CUE-102, thus,
breastfeeding must be discontinued if the mother is treated with CUE-102;
- - Is receiving any form of immunosuppressive therapy (e.g. chronic systemic steroid
therapy exceeding dosage of 10 mg daily of prednisone equivalent) within 7 days
prior to enrollment;
- Has received systemic immunosuppressive treatments, aside from systemic
corticosteroids (such as methotrexate, chloroquine, azathioprine, etc), within six
months of enrollment;
- Requires treatment with high dose systemic corticosteroids defined as dexamethasone
> 2 mg/day or bioequivalent for at least 3 consecutive days within 2 weeks of
enrollment;
- Inhaled or topical steroids and adrenal replacement doses ≤ 10 mg daily
prednisone equivalents are permitted in the absence of active autoimmune
disease.
- - Participants are permitted to use topical, ocular, intra-articular, intranasal,
and inhalational corticosteroids (with minimal systemic absorption).
- - Physiologic replacement doses of systemic corticosteroids are permitted, ≤10
mg/day prednisone equivalents.
- - A brief course of corticosteroids for prophylaxis (eg, contrast dye allergy) or
for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity
reaction caused by contact allergen) is permitted.
- - Requires therapeutic anticoagulation with warfarin at baseline; patients must be off
warfarin or warfarin-derivative anti-coagulants for at least 7 days prior to
enrollment; however, therapeutic or prophylactic therapy with low-molecular weight
heparin is allowed;
- Has received a live vaccine within 30 days prior to enrollment;
- Examples of live vaccines include - but are not limited to - the following:
measles, mumps, rubella, varicella/zoster (chicken pox), 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 (eg, FluMist®) are live attenuated
vaccines and are not allowed.
- - History of acute pancreatitis within 3 months before enrollment;
- Diverticulitis that is clinically significant in the opinion of the Investigator
based on the extent or severity of known disease and/or the occurrence of clinically
significant flares within 4 weeks before enrollment.
