| Eligibility |
Inclusion Criteria:
1. Signed and dated PICF obtained prior to any trial-specific procedure that is not part
of standard patient care.
2. Patient is = 18 years-old at the time of PICF signature (or the legal age of consent
in the jurisdiction in which the trial is taking place).
3. Histologically or cytologically confirmed solid tumor belonging to one of the cohorts
specified in the protocol. To be eligible, patient must meet the criteria for tumor
type, stage and prior anti-cancer therapy according to the protocol.
4. Tumor must be:
- In all colorectal (CRC patients) and in any non-CRC patient with dMMR/MSI testing
available prior to enrollment: pMMR/MSS tumor based on IHC, MSI-PCR or NGS
testing, as performed at the site prior to enrollment according to site's
standard practice.
- In any non-CRC patient with unknown dMMR/MSI status: the site must confirm at
screening that the patient has available and retrievable archival tumor tissue
from the primary or metastatic site, for submission to a central laboratory for
dMMR/MSI testing.
5. Measurable disease by CT or MRI per Response Evaluation Criteria in Solid Tumors
(version 1.1), based on tumor assessment performed within 28 days of enrollment.
6. Progressive cancer at the time of trial entry based on clinical or radiographic
findings or tumor marker evaluation, according to Investigator's judgment, or cancer
that is not amenable to standard therapies even if not progressing.
7. ECOG Performance Scale score of 0 or 1 at enrollment.
8. Adequate hematologic and organ function as assessed by the following laboratory tests,
performed at screening (specified within the protocol).
9. Patient must be willing and able to comply with scheduled visits, treatment plans,
laboratory tests, and other trial procedures.
10. Women of childbearing potential (CBP) must have confirmed negative serum pregnancy
test (for ß-hCG) within 7 days prior to enrollment.
11. Women of CBP must agree to remain completely abstinent (complete avoidance of
heterosexual intercourse) or use highly effective contraceptive methods (i.e., with a
failure rate of < 1% per year) during the Treatment Phase and for at least 7 months
after the last trial treatment intervention.
12. Men who are sexually active with women of CBP must agree to remain completely
abstinent (complete avoidance of heterosexual intercourse) or use contraceptive
measures and agreement to refrain from donating sperm during the Treatment Phase and
for a total of 7 months post-treatment completion.
Exclusion Criteria:
1. Prior treatment with regorafenib.
2. Prior treatment with a PD1, PD-L1/PD-L2, or CTLA-4 inhibitor, or any other drug or
antibody targeting T-cell co-stimulation or checkpoint pathways, except in patients
that meet all the following criteria:
- Patient received a PD1, PD-L1/PD-L2, or CTLA-4 inhibitor, or any other drug or
antibody targeting T-cell co-stimulation or checkpoint pathways in either:
1. Neoadjuvant and/or adjuvant setting and had no relapse within 12 months of
completing immunotherapy
2. Advanced disease setting and had no progression during immunotherapy
- Patient tolerated immunotherapy and did not need to discontinue treatment due to
intolerable toxicity
3. Evidence of progressive or symptomatic CNS metastases. Patients with treated CNS
metastases are eligible if they meet all the following criteria:
- Minimal neurologic symptoms
- Evidence of stable disease (for at least 2 weeks prior to enrollment) or response
on a follow-up scan performed after CNS treatment completion
- Require corticosteroids at a dose = 10 mg daily of prednisone or equivalent
4. Previous treatment with live vaccine within 28 days of planned start of trial drugs
(seasonal flu vaccines that do not contain a live virus are permitted).
5. Concurrent participation in another clinical study, unless it is: (a) an observational
(noninterventional) study, or (b) the follow-up period of an interventional trial and
patient did not receive an investigational agent/device within 28 days before
enrollment (or within 5 half-lives of the drug).
6. Major surgical procedure, open biopsy, significant traumatic injury, radiation therapy
and/or systemic anti-cancer therapy =28 days prior to enrollment. Patients must have
recovered adequately from the toxicity and/or complications from these interventions
before enrollment. Radiation therapy given with palliative intent is allowable if
finalized = 14 days prior to enrollment.
7. Known hypersensitivity to any of the trial drugs or its formulation components.
8. Active autoimmune disease or history of autoimmune disease that might recur, which may
affect vital organ function or require immune suppressive treatment including systemic
corticosteroids.
9. Requirement of systemic treatment with either corticosteroids (>10 mg daily of
prednisone or equivalent) or other immunosuppressive medications = 14 days prior to
enrollment.
10. Uncontrolled diabetes or > Grade 1 laboratory test abnormalities in potassium, sodium,
or calcium despite standard medical management or = Grade 3 hypoalbuminemia, = 14 days
prior to enrollment.
11. Interstitial lung disease, non-infectious pneumonitis or uncontrolled lung diseases
including pulmonary fibrosis, or clinically significant acute lung diseases.
12. Any cardiovascular conditions as listed within the protocol.
13. Infection requiring systemic (oral or i.v.) antibacterial, antifungal or antiviral
therapy =14 days prior to enrollment.
14. Patient unable to swallow and retain oral medication or has impairment of
gastrointestinal function or gastrointestinal disease that may significantly alter the
absorption of the oral trial treatment (e.g., uncontrolled ulcerative diseases,
uncontrolled nausea, vomiting or diarrhea, malabsorption syndrome, small bowel
resection).
15. Prior allogeneic stem cell transplantation or organ transplantation.
16. Evidence or history of bleeding diathesis or any hemorrhage or bleeding event > NCI
CTCAE v5.0 Grade 3 within 4 weeks prior to enrollment.
17. Non-healing wound, ulcer, or bone fracture.
18. Patient has a concurrent invasive malignancy or a prior invasive malignancy whose
treatment was completed within 2 years before enrollment. Note: patients with prior or
concurrent adequately treated, basal or squamous cell skin carcinoma or adequately
treated in situ carcinomas are eligible.
19. Patient has known active HBV or HCV.
20. Patient has HIV infection, unless they meet certain criteria (listed within the
protocol).
21. Persistent proteinuria of NCI CTCAE v5.0 Grade 3. Urine dipstick result of = 3+ is
allowed if protein excretion (estimated by urine protein/creatinine ratio on a random
urine sample) is < 3.5 g/24 hours.
22. Unresolved clinically significant toxicity (per Investigator's assessment) greater
than NCI CTCAE v5.0 Grade 1 attributed to any prior therapy/procedure, excluding
alopecia of any grade and non-painful peripheral neuropathy grade = 2 (according to
NCI CTCAE v5.0).
23. Patient has any other concurrent severe and/or uncontrolled medical condition or
personal, psychological, geographic or social circumstance, that would, in the
Investigator's judgment, cause unacceptable safety risks, contraindicate patient
participation in the clinical trial or compromise compliance with the protocol and
retention.
24. Pregnant or breast-feeding (lactating) women or women who plan to become pregnant or
breast-feed during the trial.
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