Clinical Drug Experience Knowledgebase

Criteria

General Inclusion Criteria:

Patients with a pathologically confirmed diagnosis of advanced solid tumors or lymphoma.
Tumor progression after receiving standard/approved therapies which may include chemotherapy, targeted agents, radio-immuno conjugates, check point inhibitors, where there is no approved therapy; or the patient is intolerant of standard of care or the patient declines standard of care treatment
One or more metastatic tumors measurable, or evaluable, per RECIST v1.1 Criteria for solid tumors and Lugano Criteria for lymphoma
Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
Life expectancy of at least 3 months
Age 18 years
Signed, written IRB-approved informed consent
A negative pregnancy test (if female)

Acceptable liver function:

Bilirubin ≤ 1.5 times upper limit of normal
AST (SGOT), ALT (SGPT) and Alkaline phosphatase ≤ 2.5 times upper limit of normal (if liver metastases are present, then ≤ 5 x ULN is allowed)

Acceptable renal function:

o Serum creatinine ≤ 1.5 times institutional ULN, OR calculated creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.

Acceptable hematologic status:

Granulocyte ≥ 1500 cells/mm3
Platelet count ≥ 100,000 (plt/mm3)
Hemoglobin ≥ 9 g/dL

Urinalysis:

o No clinically significant abnormalities

Acceptable coagulation status (for patients on warfarin or other anti-coagulants, a PT/PTT considered by the PI as therapeutically appropriate will be allowed):

PT within ≤ 1.5 times normal limits
PTT within ≤ 1.5 times normal limits
For men and women of child-producing potential, the use of effective contraceptive methods during the study
Fasting glucose ≤ 180 mg/dL
Albumin ≥ 3.0 g/dL within seven days of initiating protocol treatment

For patients in the GZ17-6.02 plus capecitabine Phase 1b Expansion Cohort 2 (metastatic breast cancer):

Pathologically confirmed diagnosis of HER2-negative and Hormone Receptor (HR) (estrogen receptor [ER] and/or progesterone receptor)-positive metastatic breast cancer;
Had ≤ 1 prior treatment (not including neoadjuvant or adjuvant treatment);
Are naïve to capecitabine but not necessarily to fluorouracil (5 FU);
Eligible for standard-of-care treatment with capecitabine monotherapy.
Patients in Expansion Cohort 2 with bone-only metastatic disease must have one or more lytic or a mixed lytic-blastic lesions that can be assessed by computed tomography (CT) scan or magnetic resonance imaging (MRI).

For patients in GZ17-6.02 plus capecitabine Phase 1b Expansion Cohort 3 (metastatic colorectal cancer):

Pathologically confirmed diagnosis of metastatic colorectal cancer;
Had ≤ 2 prior treatments (not including neoadjuvant or adjuvant treatment);
Are naïve to capecitabine but not necessarily to 5 FU;
Eligible for standard-of-care treatment with capecitabine monotherapy.

General Exclusion Criteria: (All patients, unless otherwise specified):

New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG.
Currently taking MAOIs
Baseline QTc exceeding 450 msec in males, 470 msec in females (using the Fridericia's formula) and/or patients receiving class 1A or class III antiarrhythmic agents;
Known active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy;
Pregnant or nursing women.
NOTE: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
Treatment with radiation therapy or surgery within 1 month prior to study entry.
Treatment with chemotherapy, targeted therapeutics (e.g. tyrosine kinase inhibitors, therapeutic antibodies, etc), or investigational therapies within 1 month, or 5 half-lives (whichever is shorter), prior to study entry (6 weeks for nitrosoureas or mitomycin C). For radiopharmaceuticals, within 1 month unless hematopoietic recovery has not returned to pretreatment baseline;
Unwillingness or inability to comply with procedures required in this protocol;
Known active infection with HIV, HTLV-1, hepatitis B, hepatitis C or other chronic viral infections that could interfere with the interpretation of study data;
Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the investigator and/or the sponsor.
Patients who are currently receiving any other investigational agent;
Primary Central Nervous System (CNS) malignancies;
Active CNS metastases requiring treatment or radiotherapy, or which have not been confirmed stable on radiographic imaging for ≥30 days prior to C1D1;
Patients requiring steroids for neurological signs and symptom stabilization.
Patients who are unable to successfully discontinue all prohibited medications listed in Appendix 6;
Patients must not have received a transfusion (platelets or red blood cells) ≤ 2 weeks prior to initiating protocol therapy.

For patients in the GZ17-6.02 monotherapy Dose Escalation Cohort and patients in Expansion Cohort 1:

• Patients with cow's milk allergy or with galactosemia

Phase 1b Expansion Cohort 2 (metastatic breast cancer) and Expansion Cohort 3 (metastatic colorectal cancer):

Any history of coronary artery disease is exclusionary; New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on the ECG.
Any conditions or medications that are contraindicated with capecitabine dosing;
Dihydropyrimidine dehydrogenase (DPD) deficiency;
Known sensitivity to capecitabine or any of its components or to 5-FU ;

Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the investigator and/or the sponsor

o This includes prior gastrointestinal surgery that would interfere with the oral drug absorption.

Malignancy other than metastatic breast cancer (Expansion Cohort 2) or metastatic colorectal cancer (Expansion Cohort 3) that required therapy within the preceding 5 years, other than adequately treated:

non-melanoma skin cancer or in situ cancer;
another cancer that has a very low risk of interfering with the safety or efficacy endpoints of the study, must be approved by the Sponsor medical team.