study evaluating gz17-6.02 in patients with advanced solid tumors or in combination with capecitabine in metastatic hormone receptor positive breast cancer

Conditions: Advanced Cancer; Gastric Cancer; Breast Cancer; Pancreatic Cancer; Prostate Cancer Metastatic; Colo-rectal Cancer; Solid Tumor; Solid Carcinoma; Solid Carcinoma of Stomach; Cancer of Stomach; Lymphoma; Sarcoma; Cutaneous T Cell Lymphoma; Head and Neck Squamous Cell Carcinoma; Basal Cell Carcinoma; Cutaneous T-cell Lymphoma; Cutaneous Squamous Cell Carcinoma

Summary: this phase i/ib study is a multicenter, open-label, dose-escalation, safety, pharmacodynamic and pharmacokinetic study of gz17-6.02 monotherapy and in combination with capecitabine, given orally on a daily schedule in patients with advanced solid tumors or lymphoma

this study will evaluate the safety, pharmacokinetics, and pharmacodynamic effects of a novel anti-cancer drug, gz17-6.02 administered to patients with advanced solid tumors or lymphoma, which have progressed after receiving standard/approved therapy or where there is no approved therapy. this study will determine the maximum tolerated dose (mtd) and the dose limiting toxicities (dlt) of gz17-6.02 monotherapy and in combination with standard-of-care oncology treatments and to establish the dose of gz17-6.02 recommended for future monotherapy and combination therapies phase ii oncology clinical studies.

Eligibility 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.