| Eligibility |
Inclusion Criteria:
1. Histological confirmation of CRC
2. Post-R0 resection of stages II, III, or IV CRC and all planned adjuvant therapies have
been completed
3. No evidence of radiographic disease within 28 days (before or after) of a positive
ctDNA assay
4. Evident MRD as defined by positive ctDNA assay. Patients may be identified for
enrollment with any Clinical Laboratory Improvement Amendments (CLIA)-certified ctDNA
assay for MRD. MRD status will be confirmed with the Signatera assay prior to
initiation of therapy (unless the prior testing was also done with Signatera in which
case this test would not require confirmation)
5. Adequate organ and marrow function as defined below:
1. Absolute neutrophil count: =1,000/mcL
2. Platelets: =100,000/mcL
3. Total bilirubin =1.5 x the upper limit of normal (ULN). Total bilirubin (=3 x
ULN) is allowed if Gilbert's syndrome is documented.
4. AST(SGOT)/ALT(SGPT): =3 × institutional ULN (=5 x ULN for patients with liver
involvement of their cancer).
5. Creatinine clearance =40 mL/min. Creatinine clearance (Clcr) can either be
measured in a 24-hour urine collection or estimated by the Cockcroft-Gault
equation as follows: Clcr (mL/min) = [(140 - age) x (weight in kg) ÷ [72 x (serum
creatinine in mg/dL)] [0.85 if female]
6. ECOG performance status (PS) of 0 or 1 (Appendix A)
7. Age = 18 years. Because no dosing or adverse event data are currently available on the
use of regorafenib in these patients, children <18 years of age are excluded from this
study.
8. Able to understand and is willing to sign a written informed consent document.
9. The effects of Regorafenib and XmAb20717 on the developing human fetus are unknown.
For this reason and because regorafenib appears to be teratogenic in animal models,
women of child-bearing potential (refer to MDA Policy CLN 1114) must agree to use
adequate contraception (hormonal or barrier method of birth control; abstinence) prior
to study entry, for the duration of study participation and for at least 4 months
after the last dose. This includes all female patients, between the onset of menses
(as early as 8 years of age) and 55 years unless the patient presents with an
applicable exclusionary factor which may be one of the following:
- Postmenopausal (no menses in greater than or equal to 12 consecutive months).
- History of hysterectomy or bilateral salpingo-oophorectomy.
- Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range,
who have received Whole Pelvic Radiation Therapy).
- History of bilateral tubal ligation or another surgical sterilization procedure.)
Approved methods of birth control are as follows: Hormonal contraception (i.e.
birth control pills, injection, implant, transdermal patch, vaginal ring),
Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post
vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide.
Not engaging in sexual activity for the total duration of the trial and the drug
washout period is an acceptable practice; however periodic abstinence, the rhythm
method, and the withdrawal method are not acceptable methods of birth control.
Should a woman become pregnant or suspect she is pregnant while she or her
partner is participating in this study, she should inform her treating physician
immediately. Men treated or enrolled on this protocol must also agree to use
adequate contraception prior to the study, for the duration of study
participation, and 4 months after completion of administration.
Exclusion Criteria:
1. Concurrent treatment with drug with which the interactions are considered clinically
significant by investigator (as outlined in section 5.2). Major surgical procedure or
significant traumatic injury within 21 days before start of study medication. Note: If
participants received major surgery, they must have recovered adequately from the
toxicity and/or complications from the intervention prior to starting therapy
2. Systemic therapy with immunosuppressive agents within 7 days or use of any
investigational drug within 28 days before the start of trial treatment.
3. Prior exposure to any immune checkpoint blockade agent or any other immunomodulatory
agent used for antineoplastic therapy for mCRC.
4. Previous malignant disease (other than the target malignancy to be investigated in
this trial) within 3 years prior to study treatment initiation.
5. Receipt of any organ transplantation, including allogeneic stem cell transplantation
(exception: transplants that do not require immunosuppression, such as hair
transplant).
6. Active autoimmune disease that might deteriorate when receiving an immunostimulatory
agent.
7. Known severe hypersensitivity reactions to monoclonal antibodies (Grade = 3 NCI-CTCAE
v4.03), any history of anaphylaxis, or recent (within 5 months) history of
uncontrolled asthma.
8. Clinically significant cardiovascular/ cerebrovascular disease as follows: 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 serious cardiac arrhythmia.
9. Clinically relevant diseases (for example, inflammatory bowel disease) and / or
uncontrolled medical conditions, which, in the opinion of the Investigator, might
impair the subject's tolerance or ability to participate in the trial.
10. Failure to recover from any other toxicity (other than immune-related toxicity)
related to previous anticancer treatment to = Grade 2.
11. Receipt of a live-virus vaccine within 30 days prior to first dose of study drug
(seasonal flu vaccines that do not contain live virus are permitted).
12. Evidence of any serious bacterial viral (active HIV, HCV or HBV), parasitic, or
systemic fungal infections within the 30 days prior to the first dose of study drug.
13. Subject is pregnant or breast feeding or planning to become pregnant while enrolled in
the study, up to the final EOT visit.
14. History of (non-infectious) pneumonitis that required steroids, ongoing pneumonitis,
or history of interstitial lung disease.
15. Grade > 3 proteinuria ( > 3.5 g/24 hours)
16. Grade > 3 hypertension (systolic blood pressure > 160 or diastolic blood pressure >
100).
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