| Eligibility |
Inclusion Criteria:
1. Male or female patient age = 18 years with a history of treated colorectal cancer with
unresectable metastases of the primary colorectal cancer to the other organs.
2. Demonstrate CCR5 + by IHC (>10% membranous staining completed at the reference
laboratory of Dr. Hallgeir Rui at Medical College of Wisconsin).
Note: This test will be done as part of the pre-screening period. It will be performed
in archival metastatic tissue.
3. Histologically confirmed for microsatellite stable MSS colorectal cancer by
Immunohistochemistry (IHC) or Next-generation sequencing (NGS)
4. Metastatic colorectal cancer (CRC) who have been previously treated with
fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, VEGF antibody, and,
if RAS wild-type, an anti-EGFR therapy Note: Prior Regorafenib therapy is not allowed.
5. Have measurable disease per RECIST 1.1
6. Have provided archival tumor tissue sample or newly obtained core or excisional biopsy
of a tumor lesion not previously irradiated.
7. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
8. Expected survival of at least three months
9. No chemotherapy treatment within the last four weeks or less than wash out period of
the chemotherapy agents, whichever is shorter
10. Patients must have adequate organ and bone marrow function within 28 days prior to
registration, as defined below:
- Leukocytes = 3,000/mcL;
- Absolute neutrophil count = 1,500/mcL;
- Platelet count > 75,000/mm^3
- Total bilirubin: within normal institutional limits;
- AST(SGOT) &ALT(SPGT) = 2.5 X institutional upper limit of normal (ULN)
(applicable to all patients, irrespective of liver disease or metastasis); and
- Creatinine: within normal institutional limits.
11. Clinically normal resting 12-lead ECG at Screening Visit or, if abnormal, considered
not clinically significant by the Principal Investigator.
12. Both male and female patients and their partners of childbearing potential must agree
to use two medically accepted methods of contraception (e.g., barrier contraceptives
[male condom, female condom, or diaphragm with a spermicidal gel], hormonal
contraceptives [implants, injectables, combination oral contraceptives, transdermal
patches, or contraceptive rings], or one of the following methods of birth control
(intrauterine devices, tubal sterilization or vasectomy) or must practice complete
abstinence from intercourse of reproductive potential from study entry to 6 months
after the last day of treatment (excluding women who are not of childbearing potential
and men who have been sterilized).
13. Females of child-bearing potential (FOCBP) must have a negative serum pregnancy test
at Screening Visit and negative urine pregnancy test prior to receiving the first dose
of study drug; and
14. Male participants must agree to use contraception and refrain from donating sperm for
at least 120 days after the last dose of study intervention.
15. Patients must have the ability to understand and the willingness to sign a written
informed consent prior to registration on study.
Exclusion Criteria:
1. Inability to understand the aims of the study and/or protocol procedures
2. Hypersensitivity towards Regorafenib or Leronlimab (PRO 140).
3. History of severe allergic, anaphylactic, or other hypersensitivity reactions to
humanized monoclonal antibodies
4. Any other concurrent antineoplastic treatment including irradiation (local radiation
of single non-target lesions for palliation only allowed)
5. Any condition requiring continuous systemic treatment with either corticosteroids (>10
mg daily prednisone equivalents) or other immunosuppressive medications within 2 weeks
prior to first dose of study treatment. Inhaled or topical steroids and physiological
replacement doses of up to 10 mg daily prednisone equivalent are permitted in the
absence of active autoimmune disease.
6. Clinically significant active coronary heart disease and cardiovascular insufficiency
with hypotension (systolic blood pressure <100 mmHg) per PI discretion.
7. Cardiac arrhythmias requiring anti-arrhythmic therapy; Note: pace makers, beta
blockers, or digoxin are permitted
8. Any GI or Respiratory system disorders that per PI discretion can interfere with the
study treatment or jeopardize the patient's health.
9. Prior allogeneic bone marrow transplantation
10. Administration of a live, attenuated vaccine within four weeks prior to start of
maintenance treatment or anticipation that such a live attenuated vaccine will be
required during the remainder of the study Note: Seasonal influenza vaccines for
injection are generally inactivated flu vaccines and are allowed; however intranasal
influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not
allowed.
11. Positive test for human immunodeficiency virus (HIV) or HIV infection
12. Active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg]
test) or hepatitis C. Note: Patients with past hepatitis B virus (HBV) infection or
resolved HBV infection (defined as having a negative HBsAg test and a positive
antibody to hepatitis B core antigen antibody test) are eligible.
13. Active or latent tuberculosis
14. Clinically active brain metastases, defined as untreated symptomatic, or requiring
therapy with steroids or anticonvulsants to control associated symptoms.
15. Patient who have an active infection requiring systemic therapy.
16. Patient who are taking strong CYP3A4 inducers (e.g. rifampin, phenytoin,
carbamazepine, phenobarbital, and St. John's Wort) or strong CYP3A4 inhibitors (e.g.
clarithromycin, grapefruit juice, itraconazole, ketoconazole, nefazodone,
posaconazole, telithromycin, and voriconazole)
17. Are pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the study, starting with the Screening Visit through 120 days
after the last dose of study intervention.
18. Have undergone major surgery and have not recovered adequately from any toxicity
and/or complications from the intervention before starting study intervention.
19. Have a seizure disorder requiring ongoing antiseizure therapy or with any condition
that, in the judgment of the investigator, is likely to increase the risk of seizure
(e.g., CNS malignancy.)
20. Have received prior therapy with Leronlimab or any other CCR5 antagonist (e.g.,
maraviroc).
21. Have received prior therapy with regrafenib.
22. Have been treated with an agent directed to another stimulatory or co-inhibitory
T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX 40,
CD137).
23. Patient who received prior radiotherapy (not to target lesions) within 3 weeks of
start of study intervention.
24. Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy or used an investigational
device within 28 days prior to enrollment;
25. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial
|
