Dose Escalation, First-in-human Clinical Trial to Evaluate the Safety, Pharmacokinetics and Preliminary Antitumor Activity of PEP-010, Administered as Single Agent and in Combination With Paclitaxel or With Gemcitabine in Patients With Metastatic Solid Cancer
This is an open-label, non-controlled, multicenter, dose escalation, first-in-human phase I clinical trial with an expansion phase designed to assess the safety, tolerability, PK and PD parameters, and preliminary antitumor activity of intravenous dosing of PEP-010 as single agent and in combination with paclitaxel or with gemcitabine PEP-010 will be administered, in a Part 1, as single agent in patients with solid cancers who are not amenable to standard treatment, or in combination in patients who are eligible for the paclitaxel therapy, and in a Part 2 only in combination in: Cohort 1 (expansion cohort, phase 1b): metastatic pancreatic ductal carcinoma (PDAC) who received at least one previous systemic chemotherapy and eligible for paclitaxel therapy. Cohort 2 (dose escalation cohort, phase 1a): metastatic pancreatic ductal carcinoma or advanced/metastatic ovarian cancer (OC) eligible for gemcitabine-based therapy
• Part 1 Arms A and B:
• Arm A: Patients must have histologically confirmed diagnosis of recurrent and/or metastatic solid tumors, who are not amenable to standard therapy, with exceptions as defined in the non-inclusion criteria,
• Arm B: Patients must have histologically confirmed diagnosis of recurrent and/or metastatic solid tumors. Patients must be eligible for a treatment with paclitaxel as single agent. Patients who are eligible for standard of care paclitaxel-based combination therapy should not be included in the trial unless they have been previously exposed to that specific combination therapy. Specifically :
‣ Patients with ovarian cancer must have received prior therapy with paclitaxel as part of standard of care in combination with carboplatin.
⁃ Patients with triple negative breast cancer are eligible for the trial since paclitaxel as single agent is standard of care in this disease.
• Age ≥ 18 years,
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1,
• Patients must have measurable disease (as per RECIST version 1.1),
• Patient ability to comply with the collection of tumor biopsies, and tumors must be accessible for biopsy,
• Adequate bone marrow function as defined by: Absolute Neutrophil Count (ANC) of ≥ 1.5 x 109/L, platelet count of ≥ 100 x 109/L, and hemoglobin of ≥ 9 g/dL),
• Adequate liver function, as determined by a serum total bilirubin ≤ 1.5 Upper Limit of Normal (ULN), AST and ALT ≤ 3 x ULN (≤ 5 x ULN if liver metastases),
• Adequate renal function, as determined by a serum creatinine ≤ 1.5 x ULN,
⁃ Provision of signed written informed consent,
⁃ Patient ability to comply with protocol requirements,
⁃ If the patient is female:
∙ Patient must be postmenopausal, surgically sterile, or they must agree to use a physical barrier method of contraception in addition to either an intrauterine device or hormonal contraception until at least 6 months after termination of study drug or must refrain from heterosexual activity during this same period.
‣ Patients of childbearing potential must have a negative pregnancy test within the seven days prior to the first study drug administration.
⁃ If the patient is male:
⁃ \- Patient must abstain from heterosexual activity or must agree to use an acceptable method of contraception (e.g., condom) during the study for at least 6 months after termination of study drug.
⁃ Patients covered by a health insurance system;
• Part 2 Cohort 1 Pancreatic Ductal adenocarcinoma (PDAC)
• Age ≥ 18 years,
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1,
• Patients must have measurable disease (as per RECIST version 1.1),
• Patient ability to comply with the collection of tumor biopsies, and tumors must be accessible for biopsy,
• Adequate bone marrow function as defined by: Absolute Neutrophil Count (ANC) of ≥ 1.5 x 109/L, platelet count of ≥ 100 x 109/L, and hemoglobin of ≥ 9 g/dL),
• Adequate liver function, as determined by a serum total bilirubin ≤ 1.5 Upper Limit of Normal (ULN), AST and ALT ≤ 3 x ULN (≤ 5 x ULN if liver metastases),
• Adequate renal function, as determined by a serum creatinine ≤ 1.5 x ULN,
• Provision of signed written informed consent,
• Patient ability to comply with protocol requirements,
⁃ If the patient is female:
∙ Patient must be postmenopausal, surgically sterile, or they must agree to use a physical barrier method of contraception in addition to either an intrauterine device or hormonal contraception until at least 6 months after termination of study drug or must refrain from heterosexual activity during this same period.
‣ Patients of childbearing potential must have a negative pregnancy test within the seven days prior to the first study drug administration.
⁃ If the patient is male:
⁃ \- Patient must abstain from heterosexual activity or must agree to use an acceptable method of contraception (e.g., condom) during the study for at least 6 months after termination of study drug.
⁃ Patients covered by a health insurance system
⁃ Histologically confirmed metastatic pancreatic ductal adenocarcinoma (mixed histology is acceptable as long adenocarcinoma is the dominant histological subtype)
⁃ Patient should have received at least one previous line of systemic treatment in metastatic setting
⁃ No previous disease progression under taxane therapy or 12-month free interval since last taxane therapy.
• Part 2 Cohort 2 Pancreatic Ductal adenocarcinoma (PDAC) or Ovarian Cancer (OC)
• Age ≥ 18 years,
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1,
• Patients must have measurable disease (as per RECIST version 1.1),
• Patient ability to comply with the collection of tumor biopsies, and tumors must be accessible for biopsy,
• Adequate bone marrow function as defined by: Absolute Neutrophil Count (ANC) of ≥ 1.5 x 109/L, platelet count of ≥ 100 x 109/L, and hemoglobin of ≥ 9 g/dL),
• Adequate liver function, as determined by a serum total bilirubin ≤ 1.5 Upper Limit of Normal (ULN), AST and ALT ≤ 3 x ULN (≤ 5 x ULN if liver metastases),
• Adequate renal function, as determined by a serum creatinine ≤ 1.5 x ULN,
• Provision of signed written informed consent,
• Patient ability to comply with protocol requirements,
⁃ If the patient is female:
∙ Patient must be postmenopausal, surgically sterile, or they must agree to use a physical barrier method of contraception in addition to either an intrauterine device or hormonal contraception until at least 6 months after termination of study drug or must refrain from heterosexual activity during this same period.
‣ Patients of childbearing potential must have a negative pregnancy test within the seven days prior to the first study drug administration.
⁃ If the patient is male:
⁃ \- Patient must abstain from heterosexual activity or must agree to use an acceptable method of contraception (e.g., condom) during the study for at least 6 months after termination of study drug.
⁃ Patients covered by a health insurance system
⁃ Patient must be eligible but not previously treatment with gemcitabine.
⁃ Specific Pancreatic Ductal adenocarcinoma (PDAC)
⁃ Histologically confirmed metastatic pancreatic ductal adenocarcinoma (mixed histology is acceptable as long adenocarcinoma is the dominant histological subtype)
⁃ Specific ovarian cancer (OC)
⁃ Patient has been diagnosed with recurrent epithelial ovarian, peritoneal, or fallopian tube carcinoma.
⁃ Subjects had disease recurrence or progression during prior chemotherapy with platinum-based regimens or within 6 months after the last dose of chemotherapy with platinum-based regimens (for at least 4 cycles of treatment)
⁃ Patient should have received at least one previous line of treatment in platinum-resistant setting.