Inclusion Criteria:
1. Aged 18 to 80 years at time of enrollment. 2. Body weight >/= 50kg. 3. Able to provide a recent tumor specimen taken within 6 months prior to signing consent
and after the initiation of the subject's most recent systemic anti-cancer therapy,
for GPC3 expression assessment by immunohistochemistry (IHC). Previously collected
tumor tissue older than 6 months at time of GPC3 IHC testing or collected prior to
initiation of current or last systemic therapy may be permitted for GPC3 prescreening.
If prescreening sample is found to be GPC3+, a new tumor biopsy will be needed to
confirm tumor remains GPC3+ in order to proceed.
4. Histologically confirmed advanced unresectable or metastatic hepatocellular carcinoma
(HCC), squamous cell carcinoma (SCC) of the lung, myxoid/round cell liposarcoma
(MRCLS), or Merkel cell carcinoma (MCC) with GPC3 overexpression by IHC. Subjects must
consent to IHC testing in a separate informed consent. Note: Tumor samples will be
sent to a central laboratory for GPC3 expression analysis.
5. Documentation of disease progression or refractory disease or intolerance to prior
lines of standard-of-care therapies. Patients with tumors with genetic alterations and
mutations (e.g., breast cancer gene, epidermal growth factor receptor mutations, and
anaplastic lymphoma kinase translocation) who have approved targeted therapies
available for their cancer will need to have been treated with such approved therapies
or refused such approved targeted therapy for their cancer prior to enrolling in this
study.
6. Life expectancy >16 weeks. 7. Have adequate organ function (renal/hepatic/pulmonary)
8. Left ventricular ejection fraction ≥50% by multiple-gated acquisition scan or
echocardiogram. 9. Eastern Cooperative Group performance status of 0 to 1. 10. For subjects with HCC:
- - No fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma histology.
- - No grade 2 or grade 3 ascites based on the European Association for the Study of
Liver guidelines.
11. A minimum of 2 sites of disease, including at least 1 site that is measurable by
RECIST 1.1 criteria to ensure sufficient disease for response assessment. At least 1
of the other lesions must be considered adequate for Protocol-required tumor biopsy.
12. Adequate wash-out of prior systemic therapy for underlying malignancy, relative to
leukapheresis:
- - Last dose of any antineoplastic treatment must be at least 2 weeks before
leukapheresis.
- - Last dose of any investigational agent must be at least 3 half-lives of the
treatment, or 28 days, before leukapheresis (whichever is shorter).
Adequate wash-out of prior systemic therapy for underlying malignancy, relative to LD
chemotherapy:
Subjects may receive an additional dose of their last received form of therapy at the same
dose and dosing schedule following leukapheresis as bridging therapy; however, the required
wash-out period prior to start of LD chemotherapy must be adhered to:
- - The last dose of systemic nitrosourea or systemic mitomycin-C must be at least 6 weeks
before the first dose of LD chemotherapy in this study.
- - For all other systemic cytotoxic chemotherapy, the wash-out must be the duration of a
full cycle of that therapy.
For example, if the prior therapy is given in 3-week
cycles, there must be at least 3 weeks between the last dose of that therapy and the
first dose of LD chemotherapy in this study. If the prior therapy is administered more
frequently than every 2 weeks, a minimum 2-week wash-out is required.
- - For biologic therapy (e.g., antibodies) the wash-out must be either the duration of
the biologic agent dosing interval, or 3 weeks, whichever is shorter.
- - For small molecule therapies, the wash-out must be 5 half-lives of the drug.
- - For any investigational agent, the wash-out must be 3 half-lives of the
investigational agent, or 4 weeks, whichever is shorter.
Note: Local radiation of lesions is allowed if indicated for palliation requiring 1 week
wash-out prior to start of BOXR1030 dosing if < 2 weeks of radiotherapy for non-central
nervous system (CNS) disease; locally treated lesions will be considered non-target
lesions. Hormone ablation is also allowed as clinically indicated.
Exclusion Criteria:
1. Prior treatment with adoptive cell therapy (e.g., CAR T-cell therapy, natural killer
cell therapy, engineered T-cell receptor therapy).
2. History of allogenic hematopoietic stem cell transplant.
3. Known untreated CNS tumors or brain metastasis. Subjects are eligible if CNS
metastases are asymptomatic, have been treated with radiotherapy for at least 1 month
prior to informed consent, are off corticosteroids and have neurologically returned to
baseline (residual signs or symptoms related to the CNS treatment are permitted).
Imaging obtained for the purpose of CNS metastases management performed during
screening must document radiographic stability of CNS lesions for at least 1 month
prior to leukapheresis and be performed after completion of any CNS directed therapy.
If brain scans are performed, magnetic resonance scans are preferred; however,
computed tomography scans are acceptable if magnetic resonance imaging is medically
contraindicated. CNS evaluation for subjects with no suspicion of brain tumors in
their history is not required for the study. Subjects with known leptomeningeal
metastases are excluded.
4. Subjects who have not recovered to < 1 or baseline from all AEs due to previous
therapies (subjects with ≤ grade 2 peripheral neuropathy that has been stable for at
least 4 weeks or < grade 2 endocrine-related AEs that has been stable for at least 4
weeks on replacement therapy).
5. Planned use of any antineoplastic treatment or investigational agent from the time of
the first dose of LD chemotherapy through the end of study participation, except for
allowed local radiation of lesions for palliation (to be considered non-target lesions
after treatment) and hormone ablation.
6. Uncontrolled or life-threatening symptomatic concomitant disease including clinically
significant gastrointestinal bleeding or pulmonary hemorrhage within 4 weeks before
screening, known symptomatic human immunodeficiency virus (HIV) positive with an
acquired immunodeficiency syndrome-defining opportunistic infection within the past 12
months prior to screening, or a current CD4 count <350 cells/µL, symptomatic active
hepatitis B or C checked at screening, or active tuberculosis therapy.
Subjects with HIV are eligible if:
- - They have received antiretroviral therapy (ART) as clinically indicated for at
least 12 months prior to starting LD therapy and have an HIV viral load less than
40 copies/mL prior to start of LD therapy.
- - They continue on ART as clinically indicated while enrolled on study.
- - CD4 counts> 350 cells/µL and CD4 counts and viral load are monitored per standard
of care by a local health care provider.
- - They are fully vaccinated against SARS-CoV-2.
7. Has received prior radiotherapy within 2 weeks of the start of BOXR1030. Subjects must
have recovered from all radiation-related toxicities, not require corticosteroids, and
not have had severe radiation pneumonitis.
8. Potentially life-threatening second malignancy requiring systemic treatment within the
last 3 years (i.e., subjects with a history of prior malignancy are eligible if
treatment was completed at least 3 years before entering the Treatment Period and the
subject has no evidence of disease) or which would impede evaluation of treatment
response.
9. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular
accident/stroke (<6 months prior to enrollment), myocardial infarction (<6 months
prior to enrollment), unstable angina, congestive heart failure (New York Heart
Association Classification Class II), or the presence of any condition that can
increase proarrhythmic risk (e.g., hypokalemia, bradycardia, heart block) including
any new, unstable, or serious cardiac arrhythmia requiring medication, or other
baseline arrhythmia that might interfere with interpretation of electrocardiograms on
study (e.g., bundle branch block).
10. Has an active infection excluding controlled HIV.
11. Has an active autoimmune disease requiring systemic (immunosuppressive) therapy.
NOTE: Additional inclusion/exclusion criteria may apply. The above information is not
intended to be an exhaustive list of considerations for potential participation in a
clinical trial.
