Study to Evaluate Efficacy of CO-1.01 as Second Line Therapy for Gemcitabine-Refractory Stage IV Pancreatic Adenocarcinoma

A Phase II, Open-Label, Multicenter Study to Evaluate the Antitumor Efficacy of CO-1.01 for Infusion as Second-Line Therapy for Gemcitabine- Refractory Patients With Stage IV Pancreatic Adenocarcinoma and No Tumor hENT1 Expression

The purpose of this study is to determine whether CO-1.01 is safe and effective for treating metastatic pancreatic cancer that did not respond to gemcitabine.

Pancreatic tumors with low hENT1 expression may show less benefit from gemcitabine compared with those with higher expression of this nucleoside transporter. Nonclinical studies indicate that CO-1.01, a gemcitabine derivative, is effective independent of such transporters. Thus patients with low or no meaningful expression of hENT1 who failed to respond to gemcitabine might derive benefit from CO1.01 before needing alternative (combination) chemotherapy. Furthermore, the PK profiles of CO-1.01 and gemcitabine are dissimilar and this may confer additional clinical benefit on CO1.01.

Inclusion Criteria:

1. Gemcitabine-refractory metastatic ductal adenocarcinoma of the pancreas

   • At least 1 measurable lesion according to RECIST 1.1 criteria
   • Computerized tomography (CT) scan ≤ 28 days prior to CO-1.01
   • First-line treatment included at least 3 doses of gemcitabine (as monotherapy or combination therapy) with the last dose administered at least 2 weeks prior to CO 1.01
   • Radiological best response of disease progression after 1st-line treatment (no radiological stable disease or better allowed at any time)
   • Patients who experienced progressive disease during (neo)-adjuvant gemcitabine-based therapy are also eligible
   • Patients who have completed previous adjuvant therapy without progression, then subsequently have a radiological best response of disease progression on 1st line gemcitabine for metastatic disease are eligible

2. No hENT1 expression in primary or metastatic tumor sample, confirmed with IHC by a core pathology laboratory prior to study entry also eligible

3. Performance Status (ECOG) 0 or 1

4. Age ≥18 years

5. Palliative radiotherapy (if administered) ≥2 weeks prior to CO-1.01

6. Adequate hematological and biological function, with no residual gemcitabine-related toxicity

7. Written consent on an Institutional Review Board (IRB)-approved IC Form prior to any study-specific evaluation

Exclusion Criteria:

1. Patients who have had stable disease, partial response or complete response to first line gemcitabine-based therapy
2. First-line chemotherapy regimen that does not contain gemcitabine
3. First-line treatment discontinued due to intolerable gemcitabine-induced toxicity
4. Second or subsequent line therapy for advanced disease. Prior exposure to CO-1.01 or prior randomization in a protocol studying CO-1.01 (e.g.,Protocol CO-101-001)
5. Tumor that cannot be evaluated for hENT1 expression or that has hENT1 staining in >50% of cells
6. Symptomatic brain metastases
7. Concomitant treatment with prohibited medications (e.g., concurrent anticancer therapy including other chemotherapy, radiation, hormonal treatment [except corticosteroids and megestrol acetate], or immunotherapy) ≤14 days prior to CO-1.01
8. Exploratory laparotomy, palliative (e.g., bypass) surgery, or other procedures are not allowed <14 days prior to CO-1.01 administration; stenting procedures are permissible at any time prior to dosing; in all cases, the patient must be sufficiently recovered and stable
9. History of allergy to gemcitabine or eggs
10. Females who are pregnant or breastfeeding
11. Refusal to use adequate contraception for fertile patients (females and males during the study and for 6 months after the last dose of CO-1.01)
12. Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study (e.g., substance abuse, psychiatric disturbance, uncontrolled intercurrent illness including active infection, arterial thrombosis, or symptomatic pulmonary embolism)
13. Any other reason for which the investigator considers the patient should not participate in the study