Metastatic Non-Familial Adenocarcinoma Maintenance Therapy With DZ-002: Heptamine Carboxymethine Dye Conjugate

This is an open label, non-randomized, Phase 2 study to asses the efficacy, safety, PK and pharmacodynamic study of DZ-002 in patients with metastatic pancreatic adenocarcinoma who have completed four or more months of first line chemotherapy with a response of stable disease, partial response, or complete response as documented by CT.

There are two parts in this study, a dose escalation part and a dose expansion part. In the dose escalation part of this study, participants will receive one of three different doses of the study drug DZ-002: 5 mg/kg, 6 mg/kg, or 7 mg/kg. Participants will receive the study drug intravenously (into a vein) over a 4-hour period on Days 1, 8, 15, and 22 of a 4-week period. This 4-week period (28 days) is referred to as a cycle.

The first 3 to 6 participants taking part in this study will get the lowest dose of 5 mg/kg. If the drug does not cause worrisome side effects, the next group of 3 to 6 participants in the study will get a higher dose of 6 mg/kg. If the drug does not cause worrisome side effects, the last group of 3 to 6 participants will receive the highest dose of 7 mg/kg. The investigator will watch each group carefully as they increase the dose. The dose will increase for each group until participants have worrisome side effects that require the dose to be lower. Once the highest dose with manageable side effects is found, the dose escalation is stopped.

In the dose expansion part of this study, the highest dose with manageable side effects will be given to 30 more participants. This will help the investigators better understand the side effects that may happen with this drug.

Participation in this study is divided into different visits:

• Screening Visits
• Treatment Visits
• End of Treatment Visits
• Post-Treatment Visits

Various tests are run during each of these different visits as described below:

• Collection of medical history and current medications
• Physical exam, height, weight, vital signs
• Lung function tests
• CT scans or PET scans
• Heart function tests, such as Echocardiogram or multiple-gated acquisition
• Electrocardiograms (ECG)
• Blood draws for routine lab tests
• Additional blood samples to measure the amount of study drug in blood
• Urine collection
• X-ray, if indicated
• Tumor biopsy, optional
• Pregnancy test, if applicable

Inclusion criteria

• Histopathologically confirmed diagnosis of metastatic pancreatic adenocarcinoma who completed 4 months or more of first line chemotherapy and have achieved at least SD documented by CT scan.
• Male or female patients ≥18 years of age;
• Measurable or evaluable disease by RECIST v 1.1;
• Capable of understanding and complying with protocol requirements;
• A life expectancy of greater than 8 weeks at Screening;
• ECOG PS of 0 to 1;
• Written informed consent from the patient or the patient's legally acceptable representative prior to the initiation of any study procedures;
• Adequate bone marrow, liver, and renal function as defined below:

• Hemoglobin ≥ 10.0 g/dL (transfusions and/or erythropoietic stimulating growth factors allowed);
• Absolute neutrophil count ≥ 1500/μL;
• Platelet count ≥ 75,000/ μL;
• Alanine aminotransferase and aspartate aminotransferase ≤ 2.5 × the upper limit of normal (ULN) or ≤ 5 × ULN for patients with known hepatic metastases;
• Total serum bilirubin ≤ 1.5× ULN or ≤ 2 .0 × ULN if liver metastases are present. Patients with a known history of Gilbert's syndrome (≤ 3.0 × ULN)
• Estimated creatinine clearance ≥ 40 mL/min (using the Cockcroft Gault formula);
• Adequate cardiac function as estimated by left ventricular ejection fraction (LVEF) > 50% by multiple-gated acquisition (MUGA) or echocardiogram (ECHO);
• Adequate pulmonary function tests with FEV 1 >90% and Vital capacity >90%

Exclusion criteria

• New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, a history of risk factors for Torsades de Points, including heart failure, hypokalemia, and family history of long QTc syndrome, or evidence of ischemia on ECG;
• Baseline QTc exceeding 470 msec (using the Fridericia's formula) and/or patients receiving Class 1A or Class III antiarrhythmic agents or concomitant medications that prolong the QT/QTc interval;
• Patients with individual pulmonary metastases > 5 cm diameter or with high metastatic burden to the lungs as determined by the principal or the primary investigator;
• Patients with extensive bone metastases as determined by the principal or the primary investigator;
• Patients with a current positive COVID-19 diagnosis, or are currently symptomatic with COVID-19, or who have had COVID-19 in the last month, or with a history of COVID-19 diagnosis with respiratory complications;
• Active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy;
• Treatment with simvastatin unless it can be stopped prior to and during the study;
• Treatment with strong inhibitors and inducers of CYP3A4 or narrow therapeutic index substrates of CY3A4, CYP2B6, CYP1A2, CYP2C9, and CYP2C8, unless these can be stopped prior to and during the study;
• Known sensitivity to DZ-002 or its excipients;
• Pregnant (confirmed by serum or urine pregnancy test) or is breast feeding;
• Unwillingness or inability to comply with procedures required in this protocol;
• Known infection with human immunodeficiency virus and CD4 lymphocyte count ≤ 200 cells/mm3, active hepatitis B virus, or hepatitis C virus infections;
• 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
• Patients with G6PD deficiency or hereditary methemoglobinemia
• Patients taking the following medications: Nitroglycerine, dapsone or antimalarials (e.g. chloroquine, primaquine)
• Patients with known pulmonary disease