| Eligibility |
Inclusion Criteria:
- All patients must meet the following criteria for inclusion:
1. Age 18 years or older
2. Patients with evidence of recurrent or refractory colorectal, HR+,
triple-negative breast cancer (TNBC), non-small cell lung cancer (NSCLC),
pancreatic cancer, head and neck squamous cell carcinoma (HNSCC), or metastatic
melanoma, bladder/urothelial, gastric, esophageal, renal cell, hepatic, ovarian
or other solid tumors deemed medically safe to undergo serial biopsies.
3. Must have received or be ineligible for all standard of care therapies as deemed
appropriate by the treating physician.
4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
5. Adequate organ and marrow function as defined below:
- Hemoglobin = 9.0 g/dL
- Absolute neutrophil count (ANC) = 1.5 × 109
/L (> 1500 per mm3
- Platelet count = 75 × 109
/L (> 75,000 per mm^3)
- Serum bilirubin less than or equal to 1.5 × institutional upper limit of
normal (ULN).
- AST (SGOT)/ALT (SGPT) less than or equal to 2.5 × institutional ULN
- Creatinine clearance (CL) > 40 mL/min by the Cockcroft-Gault formula
(Cockcroft and Gault 1976)
- Women of childbearing potential (WCBP) must have a negative serum or urine
pregnancy test within 3 days prior to treatment. NOTE: Females are
considered of childbearing potential unless they are surgically sterile
(have undergone a hysterectomy, bilateral tubal ligation, or bilateral
oophorectomy) or are postmenopausal (at least 12 consecutive months with no
menses without an alternative medical cause)
6. Patients and their partners must practice approved forms of contraception.
Sexually active WCBP must agree to use a highly effective method of contraception
prior to study entry and continuing for 30 days after ORB-011 administration.
Highly effective methods of contraception are highly effective birth control
methods with a failure rate of < 1% per year when used consistently and
correctly. Additionally, male patients should refrain from donating sperm for 3
months following the last dose of study drug.
7. Ability to understand and willingness to sign an Institutional Review Board
(IRB)- approved written informed consent document (or that of legally authorized
representative, if applicable)
Exclusion Criteria:
- Exclusion Criteria:
Patients are to be excluded from the study if they meet any of the following criteria:
1. Patients who are receiving any other investigational agents
2. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to ORB-011 or its excipients.
3. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.
Urinary tract infections (UTIs) are excluded from being an exclusion criterion for
treatment unless they are Grade 3 or higher.
4. Pregnant women are excluded from this study because the effects of ORB-011 on a
pregnant woman or fetus are unknown. Breastfeeding should be discontinued as the
potential risk for AEs in nursing infants treated with ORB-011 is unknown.
5. Patients with hydronephrosis, except for those patients where hydronephrosis has been
longstanding (ie, predates the diagnosis of the CIS, Ta, or T1 by more than 2 years)
and diagnostic evaluation at screening shows no evidence of tumor causing the
hydronephrosis
6. Any other anticancer therapy (eg, chemotherapy, biologic therapy, immunotherapy,
targeted therapy, endocrine therapy, radiation therapy, intravesical therapy,
investigational agent) within 28 days or 5 half-lives (whichever is shorter) of the
study treatment
7. The patient has a diagnosis of another malignancy within 2 years before the first dose
of study treatment, except for superficial skin cancer, localized prostate cancer on
active surveillance, or localized solid tumors deemed cured by surgery and not treated
with systemic anticancer therapy and not expected to require anticancer therapy in the
next 2 years
8. Current or prior use of immunosuppressive medication within 28 days before ORB-011
treatment with the exceptions of intranasal and inhaled corticosteroids or systemic
corticosteroids at physiological doses, which are not to exceed 10 mg/day of
prednisone, or an equivalent corticosteroid
9. Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [eg. colitis or Crohn s disease], systemic lupus
erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with
polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]).
The following are exceptions to this criterion:
- Patients with vitiligo or alopecia
- Patients with hypothyroidism stable on hormonal replacement
- Patients without active disease in the last 5 years may be included
- Patients with celiac disease controlled by diet alone
10. History of primary immunodeficiency
11. History of allogeneic organ transplant
12. History of hypersensitivity to interferon alpha 2b or any excipient
13. Active infection with:
- Tuberculosis (clinical evaluation that includes clinical history, physical
examination, and radiographic findings, and PPD testing if indicated),
- Hepatitis B (HBV) or hepatitis C Virus (HBC): Patients with active HBV infection
or active HCV infection are ineligible. However, patients with a history of HBV
infection who have undetectable or low levels of HBV DNA and normal ALT are
eligible. Patients with chronic HBV infection who meet the criteria for anti-HBV
therapy are eligible if they have initiated anti-HBV therapy prior to treatment
with ORB-011.
Patients with a history of HCV infection are eligible if they have completed curative
antiviral treatment and have a viral load that is below the limit of detection.
- HIV: Patients living with HIV infection are ineligible only if they have a CD4
count less than 350 cells/µL and a history of an AIDS-defining infection within
the last 12 months. Patients with a CD4 count greater than 350 cells/µL or who
have not had an AIDS-defining infection within the last 12 months are eligible.
Eligible patients living with HIV should maintain effective anti-retroviral
therapy.
- SARS-COV2 (PCR positive)
14. Receipt of live attenuated vaccination within 28 days prior to the study treatment
15. Any condition that, in the opinion of the investigator, would interfere with
evaluation of study treatment or interpretation of patient safety or study results
16. Patients with uncontrolled seizures
17. Any unresolved toxicity National Cancer Institute-Common Terminology Criteria for
Adverse Events (NCI-CTCAE) Grade = 2 from previous anticancer therapy with the
exception of alopecia, vitiligo, and the laboratory values defined in the inclusion
criteria
18. Patients with irreversible toxicity not reasonably expected to be exacerbated by
treatment with ORB-011 may be included only after consultation with the Principal
Investigator
19. Patients with QTcF > 480 ms
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