| Eligibility |
Inclusion Criteria:
- Patients must meet all of the following inclusion criteria to be eligible for
participation in this study:
1. = 18 years of age at the time of informed consent.
2. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 with no
deterioration over the previous 2 weeks.
3. Patients with advanced or metastatic solid tumors, histologically or
pathologically confirmed, who have progressed after all standard therapies, or
for whom no further standard therapy exists. Patients who have declined standard
therapy or have no access to standard therapy may be enrolled and the reasons for
lack of access need to be documented.
4. Patients should have at least 1 measurable lesion at baseline according to the
definition of RECIST v1.1. Lesions situated in a previously irradiated area are
considered measurable if progression has been demonstrated in such lesions.
5. Patients previously treated with anti-CTLA 4 checkpoint inhibitors or anti
programmed cell death 1 (PD-1)/L1 will also be recruited if they meet all
eligibility criteria. For anti-PD-1/L1 patients, patients must have progressed on
treatment with an anti PD 1/L1 monoclonal antibody (mAb) administered either as
monotherapy, or in combination with other checkpoint inhibitors or other
therapies. Anti PD-1/L1 treatment progression is defined by meeting all of the
following criteria:
1. Has received at least 2 doses of an approved anti-PD-1/L1 mAb.
2. Has demonstrated disease progression (PD) after PD-1/L1 as defined by RECIST
v1.1. The initial evidence of PD is to be confirmed by a second assessment
no less than 4 weeks from the date of the first documented PD, in the
absence of rapid clinical progression.
3. Progressive disease has been documented within 12 weeks from the last dose
of anti-PD-1/L1 mAb.
i. Progressive disease is determined according to iRECIST. ii. This determination
is made by the Investigator. Once PD is confirmed, the initial date of PD
documentation will be considered the date of disease progression.
6. Adequate hematologic function, defined by the following:
1. Absolute neutrophil count (ANC) = 1.5 × 109/L, without the use of
granulocyte colony stimulating factor such as filgrastim within 2 weeks
prior to study treatment.
2. Platelet count = 100 × 109/L without transfusion within 2 weeks (= 14 days)
prior to study treatment.
3. Hemoglobin = 9 g/dL without transfusion or erythropoietin within 2 weeks (=
14 days) prior to study treatment.
7. Aspartate transaminase (AST) and alanine aminotransferase (ALT) = 2.5 × upper
limit of normal (ULN), and total bilirubin = 1.5 × ULN. Exceptions: Patients who
have serum bilirubin increases due to documented underlying Gilbert's Syndrome or
familial benign unconjugated hyperbilirubinemia may be enrolled. Patients with
known liver metastases or patients with hepatocellular carcinoma may be enrolled
with AST, ALT, and/or total bilirubin = 5 × the ULN.
8. Adequate renal function defined by either a creatinine clearance = 45 mL/min (by
Cockcroft-Gault formula) or serum creatinine (SCr) = 1.5 × ULN
9. Coagulation tests, defined by the following:
1. Activated partial thromboplastin time (aPTT) = 1.5 × ULN.
2. International normalized ratio (INR) = 1.5 × ULN. Exception: INR 2 to = 3 ×
ULN is acceptable for patients on Warfarin anticoagulation.
10. Left ventricular ejection fraction (LVEF) = 50% measured by multiple-gated
acquisition (MUGA) or echocardiogram (ECHO.).
11. Previous antitumor therapy (including endocrine, chemoradiotherapy/ radiotherapy,
targeted therapy, or immunotherapy) that has ended at least 4 weeks prior to
administration of ADG116. Focal radiation therapy for symptom relief must have
been completed at least 2 weeks prior to the first dose of ADG116. Participants
must have recovered from all radiation-related toxicities, not require
corticosteroids, and not have had radiation pneumonitis. A 1-week washout is
permitted for palliative radiation (= 2 weeks of radiotherapy) to non-CNS
disease. Exception: hormonal therapy for prostate cancer is allowed (Section
6.7).
12. Previous AEs have been improved to baseline or Grade = 1 NCI CTCAE v5.0 (except
for patients with alopecia). Participants with Grade = 2 neuropathy may be
eligible. Participants with endocrine-related AEs Grade = 2 requiring treatment
or hormone replacement may be eligible.
Exclusion Criteria:
- Patients who meet any of the following criteria cannot be enrolled:
1. Pregnant or breastfeeding females.
2. Females of childbearing potential and males whose partners are of childbearing
potential who do not agree to the use of 2 forms of highly effective
contraception during the treatment period and for 6 months after the last dose of
study drug.
3. Treatment with any investigational drug within 4 weeks prior to the first dose of
study drug.
4. Grade = 3 immune-related AEs (irAEs) or irAE that lead to discontinuation of
prior immunotherapy.
5. Has known active CNS metastases and/or carcinomatous meningitis. Participants
with previously treated brain metastases may participate provided they are
radiologically stable, i.e., without evidence of progression for at least 4 weeks
by repeat imaging (note that the repeat imaging should be performed during study
screening), clinically stable and without requirement of steroid treatment for at
least 14 days prior to first dose of study treatment.
6. History of severe hypersensitivity (Grade = 3) or known to be allergic to protein
drugs or recombinant proteins or any ingredients contained in the ADG116 or
pembrolizumab drug formulation.
7. Has an active autoimmune disease that has required systemic treatment in past 2
years (i.e., with use of disease modifying agents, corticosteroids or
immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency) is not considered a form of systemic treatment and is allowed.
8. Patients requiring systemic treatment with corticosteroids (>10 mg/day prednisone
or equivalent) or other immunosuppressive medications within 21 days before the
planned first dose of study drug. Ophthalmologic, nasal, inhaled and
intra-articular injections of steroids are allowed.
9. Patients receiving granulocyte colony stimulating factor (G-CSF), granulocyte
macrophage colony stimulating factor (GM-CSF), erythropoietin, or blood (red
blood cell [RBC] or platelet) transfusion within 14 days prior to the first dose
of the study drug.
10. Any evidence of underlying liver dysfunction due to other causes; Any history of
significant alcohol abuse, alcoholic or drug-induced hepatitis, or documented
nonalcoholic steatohepatitis.
11. Active viral (any etiology) hepatitis patients are excluded. Hepatitis B virus
(HBV) carriers are ineligible. Cured Hepatitis C (HCV) (negative HCV ribonucleic
acid [RNA] test) patients may be enrolled after consulting with the Medical
Monitor.
12. Any uncontrolled active infections requiring systemic antimicrobial treatment
(viral, bacterial, or other), or uncontrolled or poorly controlled diabetes as
evidenced by Screening (baseline) HbA1c= 7.5, asthma, chronic obstructive
pulmonary disease (COPD), or other conditions that pose a risk to the patient
participating on study.
13. Has a known history of HIV infection.
14. Patients with any type of primary immunodeficiency or autoimmune disorder
requiring treatment.
15. Major surgery within 4 weeks prior to the first dose of the study drug.
16. Has had an allogeneic tissue/solid organ transplant.
17. Clinically significant cardiac conditions, including myocardial infarction within
the last 6 months, uncontrolled angina, viral myocarditis, pericarditis,
cerebrovascular accident, or other acute uncontrolled heart disease <3 months
prior to the first dose of the study drug; LVEF <50%, New York Heart Association
(NYHA) Class III or IV congestive heart failure, or uncontrolled hypertension.
18. Patients with underlying hemoglobinopathies (e.g., thalassemia) will be excluded.
19. Pulmonary embolism or deep vein thrombosis within 3 months prior to the first
dose of study drug.
20. Has received a COVID-19 vaccine within 7 days prior to the first dose of study
treatment. Has received any other live or live-attenuated vaccine within 30 days
prior to the first dose of study treatment. Note: Administration of killed
vaccines are allowed.
21. Has received a positive COVID-19 test within 14 days of Cycle 1 Day 1.
22. Has a history of (non-infectious) pneumonitis / interstitial lung disease that
required steroids or has current pneumonitis / interstitial lung disease.
23. Any known, documented, or suspected history of illicit substance abuse.
24. Any other disease or clinically significant abnormality in laboratory parameters,
including serious medical or psychiatric illness/condition, which in the judgment
of the Investigator might compromise the safety of the patient or integrity of
the study, interfere with the patient participation in the trial or compromise
the trial objectives.
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