The Efficacy and Safety of CKD516 Combined With Durvalumab in Patient Refractory Solid Tumors

NCT04696848 | Terminated Phase 1 DMC

• 1 other identifier: 2020-1485
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single center, open-label, nonrandomized, Phase 1b, dose-escalation study designed to determine maximum tolerated dose (MTD) of CKD-516 in combination with durvalumab and evaluate the safety and tolerability profile, efficacy of CKD-516 and durvalumab treatment.

Conditions

Colorectal Cancer; Solid Tumor

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose

  To determine maximum tolerated dose of CKD-516 in combination with durvalumab

  4 weeks

Secondary Outcomes (5)

• To assess the safety and tolerability profile of CKD-516 in combination with Durvalumab

  1 year

• To assess the efficacy of CKD-516 in combination with Durvalumab; Objective Response

  1 year

• Progression-free survival

  8 weeks

• Duration of response

  1 year

• Overall survival

  1 year

Other Outcomes (2)

• Translational biomarker assessments of tumor biopsy samples

  1 year

• Translational biomarker assessments obtained from blood

  1 year

Study Arms (1)

CKD-516 plus Durvalumab

EXPERIMENTAL

Stage 1 : dose escalation durvalumab (1500 mg Q4W) plus CKD-516 at dose levels (9, 11, or 13 mg/m2) Stage 2 : durvalumab (1500 mg Q4W) plus CKD-516 at recommended phase 2 dose

Drug: CKD-516 plus Durvalumab

Interventions

CKD-516 plus Durvalumab DRUG

Stage 1 : dose escalation durvalumab (1500 mg Q4W) in combination with CKD-516 at 1 of 3 planned dose levels (9, 11, or 13 mg/m2 twice a week for 3 weeks in each cycle, Q4W). Stage 2 : durvalumab (1500 mg Q4W) in combination with CKD-516 at recommended phase 2 dose (twice a week for 3 weeks in each cycle, Q4W).

Also known as: CKD-516 plus MEDI4736

CKD-516 plus Durvalumab

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Stage 1; Dose escalation cohort:
• 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.
• Age \> 20 years at time of study entry
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Must have a life expectancy of at least 12 weeks
• Body weight \>30 kg
• Adequate normal organ and marrow function as defined below:
• Haemoglobin ≥9.0 g/dL
• Absolute neutrophil count (ANC) 1.5 x (\> 1500 per mm3)
• Platelet count ≥75 x 109/L (\>75,000 per 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
• 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.
• 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.
• 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.

You may not qualify if:

• Patients with a history of hypersensitivity to the components of study drugs
• Prior exposure to any immunotherapy
• 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)
• 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.
• 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.
• 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)
• History of allogenic organ transplantation.
• 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
• 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 adverse events or compromise the ability of the patient to give written informed consent

Sponsors & Collaborators

• Tae Won Kim: lead

Study Sites (1)

Asan Medical Center

Seoul, Songpa-gu, 138-736, South Korea

Location

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MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

N-(4-(3-(1H-1,2,4-triazol-1-yl)-4-(3,4,5-trimethoxybenzoyl)phenyl)thiazol-2-yl)-2-amino-3-methylbutanamide; durvalumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Tea Won Kim

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 23, 2020
• First Posted: January 6, 2021
• Study Start: February 24, 2021
• Primary Completion: March 9, 2023
• Study Completion: March 9, 2023
• Last Updated: April 21, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)