A Phase 1, Multicenter, Single Agent Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Evidence of Antitumor Activity of CPO-100 in Adult Patients With Advanced Solid Tumors
概览
- 阶段
- 1 期
- 干预措施
- CPO-100
- 疾病 / 适应症
- Solid Tumor
- 发起方
- Conjupro Biotherapeutics, Inc.
- 入组人数
- 34
- 试验地点
- 14
- 主要终点
- Part A-1: Number of subjects with Dose Limiting Toxicities (DLTs)
- 状态
- 终止
- 最后更新
- 29天前
概览
简要总结
This is a Phase 1, multicenter, open-label, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, and preliminary evidence of antitumor activity of CPO-100 administered intravenously in cycles of 3 weekly doses with 1 week rest (1 cycle = 4 weeks) in adult patients with advanced solid tumors.
详细描述
The study has three parts. Part A-1 is a dose-escalation phase with a modified "3+3" design in patients with metastatic or unresectable advanced solid tumors to evaluate the safety, tolerability and pharmacokinetics (PK) as a single agent. Two patients will be enrolled at each of the first 2 dose levels and observed for safety during the first cycle. If there are no ≥Grade 2 treatment emergent adverse events (TEAE) that are clinically significant and attributed to the study drug as assessed by the investigator during Cycle 1 for any of the patients in the first two dose levels, the 3rd dose level and beyond will follow the traditional 3+3 design. Dose escalation during the "3+3" period for each subsequent cohort of patients will be guided by the incidence of CPO-100-related adverse events (AE) as graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) CTCAE v5.0 in the first 4 weeks of dosing \[the Dose Limiting Toxicity (DLT) evaluation period\]. In Part A-2, the starting dose for this part will be 45 mg/m2. This dose was established in Part A-1 as being that dose at which the use of Granulocyte-colony stimulating factor ()G-CSF is indicated given that the only Grade 3 treatment-related adverse events noted were related to neutropenia and was well managed with G-CSF support. Prophylactic use of G-CSF will be permitted in Cycle 1 based on the investigator judgement. This additional intervention of primary prophylaxis will be explored in order to determine if the risk of febrile neutropenia (FN) under these circumstances is reduced. Dose escalation during the 3+3 period for each subsequent cohort of patients will be guided by the incidence of CPO-100-related adverse events (AE) as graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 in the first 4 weeks of dosing (the DLT evaluation period). After the Maximum Tolerated Dose (MTD) of weekly dosing schedule has been established, a recommended Phase 2 dose will be selected based on evaluation of the PK, and safety and tolerability profile on all available Part A study data by the Safety Review Committee (SRC). The selection of the Recommended Phase 2 Dose (RP2D) will consider all available clinical and non-clinical CPO-100 data as well as relevant docetaxel published data. Part B expansion phase will further evaluate the safety and tolerability as well as the preliminary antitumor activity at the selected RP2D. Four cohorts of patients are included in Part B: * Cohort 1: taxane naïve advanced/metastatic gastric, head and neck, lung, and ovarian cancers * Cohort 2: taxane naïve advanced/metastatic breast cancer * Cohort 3: taxane naïve advanced /metastatic prostate cancer * Cohort 4: advanced/metastatic breast or ovarian cancer who have either progressed on a taxane or have developed progressive disease within 6 months of receiving a taxane. The taxane naïve patient population is defined as patients who have not received taxane or taxane-based therapies for their metastatic diseases or patients who had suboptimal taxane exposure defined as having received less than 2 cycles of taxane or taxane-based therapies due to intolerability for their metastatic diseases. Patients who have received taxane or taxane-based therapies for their neoadjuvant treatment or patients who have received taxane or taxane-based therapies for their adjuvant treatment without disease progression during treatment are also considered taxane naïve, as long as they have not received taxane or taxane-based therapies to treat the metastatic diseases. It is estimated that approximately 60 patients can be enrolled in Parts A-1 and A-2. The exact number of patients will depend on the number of dose levels tested. A total of 60 patients, 15 patients in each cohort will be enrolled in Part B. The total duration of the study is estimated to be approximately 5 years. Patients may continue receiving CPO-100 until criteria for withdrawal are met. Patients deriving clinical benefit may continue to receive study medication for as long as they are benefiting from treatment. In the event the study closes or terminates while patients are still benefiting from and receiving CPO-100, every effort will be made to continue drug supply.
研究者
入排标准
入选标准
- •Parts A-1, A-2, and B:
- •Presence of a pathologically documented (histology or cytology) locally advanced or metastatic solid tumor cancer.
- •Patients has failed at least 2 lines of conventional systemic therapy or have no other standard of care therapies available for their cancer. Prostate cancer patients should have received adenosine triphosphate (ADT) alone,(GnRH agonist, GnRH antagonist, or surgical orchiectomy and a pathway targeted agent such as abiraterone, enzalutamide, etc (castration-resistant prostate cancer). M1 disease must be present (not just biochemical recurrence).
- •Male or female patients18 years of age or older.
- •ECOG (Eastern Cooperative Oncology Group) performance status (PS) of 0, 1 or 2
- •Having at least one measurable target lesion present and documented by RECIST 1.1 for each cancer other than prostate cancer. Patients with prostate cancer may be enrolled with non-measurable disease providing the patient with a prostate-specific antigen (PSA) increase that is ≥25% and ≥2 ng/mL above the nadir, which is confirmed by a second value ≥3 weeks later, or 2 or more new bone lesions on imaging.
- •Adequate major system function defined as:
- •Bone marrow reserve:
- •Absolute neutrophil count (ANC) ≥1.5 x109/L Platelet count ≥ 100 x109/L Hemoglobin ≥9 g/dL without transfusion (the patient needs to be transfusion independent)
- •Hepatic function:
排除标准
- •Part A and B
- •Most recent chemotherapy ≤14 days or have residual NCI CTCAE greater than Grade 1 chemotherapy-related side effects, with the exception of alopecia.
- •Use of any experimental drug ≤28 days or 5 half-lives (whichever is shorter) prior to the first dose of CPO-
- •For study drugs for which 5 half-lives is ≤28 days, a minimum of 14 days between termination of the study drug and administration of CPO-100 is required.
- •Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89 and lutetium 177) administered ≤28 days or limited field radiation for palliation ≤7 days prior to starting study drug or has not recovered from side effects of such therapy.
- •Major surgical procedures ≤28 days of beginning study drug, or minor surgical procedures ≤7 days. No waiting required following port-a-cath placement.
- •Previously untreated brain metastases. Patients who have received radiation or surgery for brain metastases are eligible if therapy was completed at least 2 weeks previously and there is no evidence of central nervous system disease progression, and no requirement for chronic corticosteroid therapy.
- •Leptomeningeal metastases or spinal cord compression due to disease.
- •Known serious hypersensitivity reactions to docetaxel or life-threatening toxicity due to prior exposure to docetaxel
- •Pregnant or lactating.
研究组 & 干预措施
Part A-1: Dose Escalation
CPO-100 administered intravenously in cycles of 3 weekly doses with 1 week rest (1 cycle = 4 weeks).
干预措施: CPO-100
Part B: Cohort 1
CPO-100 administered intravenously in cycles of 3 weekly doses with 1 week rest (1 cycle = 4 weeks) at the recommended Phase 2 dose (X mg/m2) in 15 patients with taxane naïve advanced solid tumors of gastric, head and neck, lung, and ovarian.
干预措施: CPO-100
Part A-2: Dose escalation
CPO-100 administered intravenously in cycles of 3 weekly doses with 1 week rest (1 cycle = 4 weeks) with the option to administer G-CSF in cycle one. Starting dose will be 45 mg/m2.
干预措施: CPO-100
Part B: Cohort 2
CPO-100 administered intravenously in cycles of 3 weekly doses with 1 week rest (1 cycle = 4 weeks) at the recommended Phase 2 dose (X mg/m2) in 15 patients with taxane naïve advanced breast cancer.
干预措施: CPO-100
Part B: Cohort 4
CPO-100 administered intravenously in cycles of 3 weekly doses with 1 week rest (1 cycle = 4 weeks) at the recommended Phase 2 dose (X mg/m2) in 15 patients with either ovarian or/and breast cancer who have failed prior taxane treatment (ie, either progressed on a taxane regimen or within 6 months of receiving a taxane regimen).
干预措施: CPO-100
Part B: Cohort 3
CPO-100 administered intravenously in cycles of 3 weekly doses with 1 week rest (1 cycle = 4 weeks) at the recommended Phase 2 dose (X mg/m2) in 15 patients with taxane naïve advanced prostate cancer.
干预措施: CPO-100
结局指标
主要结局
Part A-1: Number of subjects with Dose Limiting Toxicities (DLTs)
时间窗: At the end of cycle 1 (each cycle is 28 days)
Incidence of dose-limiting toxicities (DLT) during the DLT evaluation period. DLTs assessed per CTCAE v5.0, include grade ≥ 4 neutropenia, thrombocytopenia, anemia; grade ≥ 3 febrile neutropenia, nausea, vomiting, diarrhea, skin rash, fatigue, infusion reaction; any other grade ≥ 2 non-hematologic toxicity judged to be dose limiting; and treatment delay \>14 days due to unresolved toxicities.
Part A-2: Number of subjects with Dose Limiting Toxicities (DLTs) when prophylactic use of G-CSF is allowed during Cycle 1
时间窗: At the end of cycle 1 (each cycle is 28 days)
Incidence of dose-limiting toxicities (DLT) during the DLT evaluation period. DLTs assessed per CTCAE v5.0, include grade ≥ 4 neutropenia, thrombocytopenia, anemia; grade ≥ 3 febrile neutropenia, nausea, vomiting, diarrhea, skin rash, fatigue, infusion reaction; any other grade ≥ 2 non-hematologic toxicity judged to be dose limiting; and treatment delay \>14 days due to unresolved toxicities.
Part B: Dose Expansion - Incidence and severity of Adverse Events
时间窗: Screening to up to 4 years
Incidence and severity of Adverse Events per CTCAE v5.0, including changes of Clinical Laboratory Values, Physical Exams, Vital Signs, Weight, Eastern Cooperative Oncology Group (ECOG) and ECG from baseline. Dosing delays and dosing intensity.
次要结局
- Tmax for CPO-100(Time Frame: 0, .5, 1, 2, 3, 4 6, 8, 24, 48 and 72 hours (Day 1) and Day 15)
- Area Under the Curve (AUC0-∞) for CPO-100(0, .5, 1, 2, 3, 4, 6, 8, 24, 48 and 72 hours (Day1))
- Cmax for CPO-100(0, .5, 1, 2, 3, 4 6, 8, 24, 48 and 72 hours (Day 1) and Day 15)
- Duration of Response (DoR)(From first PR or CR until disease progression or death up to 4 years)
- Area Under the Curve (AUC0-t) for CPO-100(0, .5, 1, 2, 3, 4, 6, 8, 24, 48 and 72 hours (Day1) and Day 15)
- Overall response rate (ORR)(At the end of every 28 day cycle for up to 4 years)
- Disease control rate (DCR)(At the end of every 28 day cycle for up to 4 years)
- Progression-Free Survival (PSF)(From first dose until documented disease progression or death up to 4 years)