None listed
Conditions
Interventions
Drug : combination with durvalumab and CKD-516
[Cohort 1] : Dose Escalation Cohorts
-Dose level 1 : CKD-516 : 9mg/m2, twice per week + Durvalumab 1500mg every 4weeks
-Dose level 2 : CKD-516 : 11mg/m
Sponsors
Asan Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Dose Escalation Cohort (Stage 1) 1. Patients with histopathologically confirmed various tumors including CRC, pancreatic cancer, cholangiocarcinoma, stomach cancer, and esophageal cancer, with measurable or non-measurable disease as determined by RECIST version 1.1, who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists. 2. Age > 20 years at time of study entry 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 4. Must have a life expectancy of at least 12 weeks 5. Body weight >30 kg 6. Adequate normal organ and marrow function as defined below: ? Haemoglobin =9.0 g/dL ? Absolute neutrophil count (ANC) 1.5 (or 1.0) x (> 1500 per mm3) ? Platelet count =75 x 109/L (>75,000 / mm3) ? Serum bilirubin =1.5 x institutional upper limit of normal (ULN). (This will not apply to patients with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician) - AST (SGOT)/ALT (SGPT) =2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be =5x ULN 7. All patients must provide and FFPE tumor sample for tissue-based IHC staining to determine TIL and other correlatives. Tumor tissue can be either from the primary tumor or metastatic biopsy. If tumor tissue is unavailable, samples should be collected with biopsy before treatment. Archived tumor specimens of =3 years are acceptable for IHC. 8. Patients must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy to the institutions’ guidelines. Patients must be willing to undergo a new tumor biopsy at screening and during therapy on this study. 9. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations. 10. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: ? Women 1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. Extension Cohorts (Stage 2) For inclusion
Exclusion criteria
Exclusion criteria: Cohort 1 & Cohort 2 :Both Dose escalation and extension cohorts, patients should not enter the study if any of the following exclusion criteria are fulfilled: 1. Patients with a history of hypersensitivity to the components of study drugs 2. Prior exposure to any immunotherapy 3. Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) = 14 days prior to the first dose of study drug (in case of nitrosoureas and/or mitomycin, within 6 weeks before study participation) 4. Any unresolved toxicity NCI CTCAE Grade =2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria - Patients with Grade =2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. - Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician. 5. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable. 6. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. (in case of VATS and/or ONC surgery, within 2 weeks before study participation) 7. History of allogenic organ transplantation. 8. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion: - Patients with vitiligo or alopecia - Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement - Any chronic skin condition that does not require systemic therapy - Patients without active disease in the last 5 years may be included but only after consultation with the study physician - Patients with celiac disease controlled by diet alone 9. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent 10. History of another primary malignancy except for - Malignancy treated with curative intent and with no known active disease =5 years before the first dose of IP and of low potential risk for recurrence - Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease - Adequately treated carcinoma in situ without evidence of disease 11. History of active primary immunodeficiency 12. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B, and hepatitis C. - Pat
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine maximum tolerated dose (MTD) in combination with durvalumab | — |
Secondary
| Measure | Time frame |
|---|---|
| To assess the safety and tolerability profile of CKD-516 in combination with Durvalumab Progression-free survival (PFS) , Duration of response (DoR);To assess the efficacy of CKD-516 in combination with Durvalumab; Objective Response Rate (ORR) determined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1);Progression-free survival, PFS;Duration of response, DoR;Overall survival, OS | — |
Countries
Korea, Republic of
Contacts
Public ContactDalnim Seo
Asan Medical Center
Outcome results
None listed