Colorectal CancerPhase 1/2NCT04696848
The Efficacy and Safety of CKD516 Combined With Durvalumab in Patient Refractory Solid Tumors
A Phase 1/2 study testing CKD-516 plus Durvalumab in people with Colorectal Cancer and Solid Tumor, run by Tae Won Kim at 1 site in South Korea.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Colorectal Cancer, Solid Tumor
- What is being tested?
- CKD-516 plus Durvalumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteSouth Korea
- Study dates
- 24 Feb 2021to 9 Mar 2023
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 22Show fewer
- 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.
- 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 <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
- Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >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)
- 1. Patients with GI cancers confirmed by histopathology or cytologic examination including CRC, pancreatic cancer, cholangiocarcinoma, stomach cancer, and esophageal cancer.
- 2~11. same above
Who cannot join
- 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)
- 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.
Show all 33Show fewer
- 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
- 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
- History of active primary immunodeficiency
- 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.
- Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients with chronic hepatitis B, confirmed by the presence of anti-HBc, receiving antiviral therapy may be enrolled if the disese is controlled for at least 1 month prior to screening. Controlled hepatitis is defined as serum HBV DNA < 2,000 IU/mL by polymerase chain reaction (PCR). Patients with controlled hepatitis B must remain on antiviral therapy, per institutional practice, to ensure adequate viral suppression, during the study.
- Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
- History of venous thrombosis within the past 3 months prior to the scheduled first dose of study treatment
- Presence of acute coronary syndrome including myocardial infarction or unstable angina pectoris, other arterial thrombotic event including cerebrovascular accident or transient ischemic attack or stroke within the past 6 months prior to the scheduled first dose of study treatment
- New York Heart Association (NYHA) Class II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, or uncontrolled hypertension(more than 160 mmHg systolic and/or more than 100 mmHg diastolic, despite appropriate antihypertensive medication
- Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
- Systemic corticosteroids at physiologic doses not to exceed <<10 mg/day>> of prednisone or its equivalent
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
- Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
- Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Study to Determine the Efficacy and Safety of CKD-516 Tablet Combined With Durvalumab(MEDI4736) in Patient Refractory Solid Tumors
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.
Read the detailed description
Dose Escalation cohort (Stage 1) With traditional 3+3 dose-escalation design, the safety, tolerability, and pharmacokinetics of CKD-516 in combination with durvalumab will be evaluated. Three dose levels of CKD-516 (9, 11, 13 mg/m2) will be investigated in combination with durvalumab 1,500 mg. At each dose level, 3 to 6 patients will be enrolled. After completion of 1 cycle of treatment of all patients in each dose level, decision for enrollment of subjects for next dose level will be decided after review of safety profile by safety review (SRM).
Extension cohort (Stage 2) Stage 2 is an exploratory study for the evaluation of the efficacy of recommended phase 2 dose (RP2D) of CKD-516 in the combination with Durvalumab in patients with specific types of solid tumors (listed below).
Arm 1: Colorectal cancer (CRC) Arm 2: Other cancer (Pancreatic cancer, Cholangiocarcinoma, Stomach cancer, Esophageal cancer)
- Conditions
- Colorectal Cancer, Solid Tumor
- Being tested
- CKD-516 plus Durvalumab
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CKD-516 plus DurvalumabDrug
Also called CKD-516 plus MEDI4736
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).
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: CKD-516 plus Durvalumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose
To determine maximum tolerated dose of CKD-516 in combination with durvalumab
Measured: 4 weeks
Secondary outcomes (5)
To assess the safety and tolerability profile of CKD-516 in combination with Durvalumab
Adverse event according to NCI CTCAE v5.0
Measured: 1 year
To assess the efficacy of CKD-516 in combination with Durvalumab; Objective Response
Objective Response Rate determined by Response Evaluation Criteria in Solid Tumors
Measured: 1 year
Progression-free survival
- Progression free survival will be measured from the start of treatment with investigational product until the first documentation of disease progression or death due to any cause, whichever occurs first.
Measured: 8 weeks
Duration of response
the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first
Measured: 1 year
Overall survival
the time from the start of treatment with investigational product until death due to any cause.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2021
- Study start24 Feb 2021
- Primary completion9 Mar 2023
- Study completion9 Mar 2023
Why it stopped: Recruitment difficulty
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (22)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tae Won Kim
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Tae Won Kim, Asan Medical Center
- Investigators
- Tea Won Kim, Principal investigator, Asan Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04696848
- Sponsor's protocol ID
- 2020-1485
- Status last verified
- Apr 2023
- First submitted
- 23 Dec 2020
- Last updated
- 21 Apr 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, Bignell GR, Bolli N, Borg A, Borresen-Dale AL, Boyault S, Burkhardt B, Butler AP, Caldas C, Davies HR, Desmedt C, Eils R, Eyfjord JE, Foekens JA, Greaves M, Hosoda F, Hutter B, Ilicic T, Imbeaud S, Imielinski M, Jager N, Jones DT, Jones D, Knappskog S, Kool M, Lakhani SR, Lopez-Otin C, Martin S, Munshi NC, Nakamura H, Northcott PA, Pajic M, Papaemmanuil E, Paradiso A, Pearson JV, Puente XS, Raine K, Ramakrishna M, Richardson AL, Richter J, Rosenstiel P, Schlesner M, Schumacher TN, Span PN, Teague JW, Totoki Y, Tutt AN, Valdes-Mas R, van Buuren MM, van 't Veer L, Vincent-Salomon A, Waddell N, Yates LR; Australian Pancreatic Cancer Genome Initiative; ICGC Breast Cancer Consortium; ICGC MMML-Seq Consortium; ICGC PedBrain; Zucman-Rossi J, Futreal PA, McDermott U, Lichter P, Meyerson M, Grimmond SM, Siebert R, Campo E, Shibata T, Pfister SM, Campbell PJ, Stratton MR. Signatures of mutational processes in human cancer. Nature. 2013 Aug 22;500(7463):415-21. doi: 10.1038/nature12477. Epub 2013 Aug 14.
PubMed 23945592Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012 Jun 28;366(26):2455-65. doi: 10.1056/NEJMoa1200694. Epub 2012 Jun 2.
PubMed 22658128Brem S, Brem H, Folkman J, Finkelstein D, Patz A. Prolonged tumor dormancy by prevention of neovascularization in the vitreous. Cancer Res. 1976 Aug;36(8):2807-12.
PubMed 1277191Butte MJ, Keir ME, Phamduy TB, Sharpe AH, Freeman GJ. Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity. 2007 Jul;27(1):111-22. doi: 10.1016/j.immuni.2007.05.016. Epub 2007 Jul 12.
PubMed 17629517Comunanza V, Bussolino F. Therapy for Cancer: Strategy of Combining Anti-Angiogenic and Target Therapies. Front Cell Dev Biol. 2017 Dec 7;5:101. doi: 10.3389/fcell.2017.00101. eCollection 2017.
PubMed 29270405Dong C, Li Z, Alvarez R Jr, Feng XH, Goldschmidt-Clermont PJ. Microtubule binding to Smads may regulate TGF beta activity. Mol Cell. 2000 Jan;5(1):27-34. doi: 10.1016/s1097-2765(00)80400-1.
PubMed 10678166Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Annu Rev Immunol. 2004;22:329-60. doi: 10.1146/annurev.immunol.22.012703.104803.
PubMed 15032581Ellis S, Carroll KJ, Pemberton K. Analysis of duration of response in oncology trials. Contemp Clin Trials. 2008 Jul;29(4):456-65. doi: 10.1016/j.cct.2007.10.008. Epub 2007 Nov 12.
PubMed 18187370Fife BT, Bluestone JA. Control of peripheral T-cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways. Immunol Rev. 2008 Aug;224:166-82. doi: 10.1111/j.1600-065X.2008.00662.x.
PubMed 18759926Hirano F, Kaneko K, Tamura H, Dong H, Wang S, Ichikawa M, Rietz C, Flies DB, Lau JS, Zhu G, Tamada K, Chen L. Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. Cancer Res. 2005 Feb 1;65(3):1089-96.
PubMed 15705911Hori K, Saito S. Microvascular mechanisms by which the combretastatin A-4 derivative AC7700 (AVE8062) induces tumour blood flow stasis. Br J Cancer. 2003 Oct 6;89(7):1334-44. doi: 10.1038/sj.bjc.6601261.
PubMed 14520469Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12293-7. doi: 10.1073/pnas.192461099. Epub 2002 Sep 6.
PubMed 12218188Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677-704. doi: 10.1146/annurev.immunol.26.021607.090331.
PubMed 18173375Lu Y, Chen J, Xiao M, Li W, Miller DD. An overview of tubulin inhibitors that interact with the colchicine binding site. Pharm Res. 2012 Nov;29(11):2943-71. doi: 10.1007/s11095-012-0828-z. Epub 2012 Jul 20.
PubMed 22814904Fens MH, Storm G, Schiffelers RM. Tumor vasculature as target for therapeutic intervention. Expert Opin Investig Drugs. 2010 Nov;19(11):1321-38. doi: 10.1517/13543784.2010.524204. Epub 2010 Oct 15.
PubMed 20946091
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study to Determine the Efficacy and Safety of CKD-516 Tablet Combined With Durvalumab(MEDI4736) in Patient Refractory Solid Tumors
- ClinicalTrials.gov ID
- NCT04696848
- Acronym / sponsor ID
- 2020-1485
- Conditions
- Colorectal Cancer, Solid Tumor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recruitment difficulty
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Tae Won KimUniversity, hospital or other
- Study start
- 24 Feb 2021 (actual)
- Primary completion
- 9 Mar 2023 (actual)
- Study completion
- 9 Mar 2023 (actual)
- First posted
- 6 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Dose Escalation cohort (Stage 1) With traditional 3+3 dose-escalation design, the safety, tolerability, and pharmacokinetics of CKD-516 in combination with durvalumab will be evaluated. Three dose levels of CKD-516 (9, 11, 13 mg/m2) will be investigated in combination with durvalumab 1,500 mg. At each dose level, 3 to 6 patients will be enrolled. After completion of 1 cycle of treatment of all patients in each dose level, decision for enrollment of subjects for next dose level will be decided after review of safety profile by safety review (SRM).
Extension cohort (Stage 2) Stage 2 is an exploratory study for the evaluation of the efficacy of recommended phase 2 dose (RP2D) of CKD-516 in the combination with Durvalumab in patients with specific types of solid tumors (listed below).
Arm 1: Colorectal cancer (CRC) Arm 2: Other cancer (Pancreatic cancer, Cholangiocarcinoma, Stomach cancer, Esophageal cancer)
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CKD-516 plus Durvalumab | Experimental | Drug: CKD-516 plus DurvalumabStage 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 |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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
Key exclusion criteria (33 listed)
- 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)
- 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
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CKD-516 plus DurvalumabAlso: CKD-516 plus MEDI4736Stage 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). | Drug | CKD-516 plus Durvalumab |
Primary outcome
Maximum tolerated dose
Time frame: 4 weeks
To determine maximum tolerated dose of CKD-516 in combination with durvalumab
5 secondary outcomes
To assess the safety and tolerability profile of CKD-516 in combination with Durvalumab
Time frame: 1 year
To assess the efficacy of CKD-516 in combination with Durvalumab; Objective Response
Time frame: 1 year
Progression-free survival
Time frame: 8 weeks
Duration of response
Time frame: 1 year
Overall survival
Time frame: 1 year
Results and safety
The study was stopped early (reason given: Recruitment difficulty). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2023.
- Background: PubMed 23945592Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, Bignell GR, Bolli N, Borg A, Borresen-Dale AL, Boyault S, Burkhardt B, Butler AP, Caldas C, Davies HR, Desmedt C, Eils R, Eyfjord JE, Foekens JA, Greaves M, Hosoda F, Hutter B, Ilicic T, Imbeaud S, Imielinski M, Jager N, Jones DT, Jones D, Knappskog S, Kool M, Lakhani SR, Lopez-Otin C, Martin S, Munshi NC, Nakamura H, Northcott PA, Pajic M, Papaemmanuil E, Paradiso A, Pearson JV, Puente XS, Raine K, Ramakrishna M, Richardson AL, Richter J, Rosenstiel P, Schlesner M, Schumacher TN, Span PN, Teague JW, Totoki Y, Tutt AN, Valdes-Mas R, van Buuren MM, van 't Veer L, Vincent-Salomon A, Waddell N, Yates LR; Australian Pancreatic Cancer Genome Initiative; ICGC Breast Cancer Consortium; ICGC MMML-Seq Consortium; ICGC PedBrain; Zucman-Rossi J, Futreal PA, McDermott U, Lichter P, Meyerson M, Grimmond SM, Siebert R, Campo E, Shibata T, Pfister SM, Campbell PJ, Stratton MR. Signatures of mutational processes in human cancer. Nature. 2013 Aug 22;500(7463):415-21. doi: 10.1038/nature12477. Epub 2013 Aug 14.
- Background: PubMed 22658128Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012 Jun 28;366(26):2455-65. doi: 10.1056/NEJMoa1200694. Epub 2012 Jun 2.
- Background: PubMed 1277191Brem S, Brem H, Folkman J, Finkelstein D, Patz A. Prolonged tumor dormancy by prevention of neovascularization in the vitreous. Cancer Res. 1976 Aug;36(8):2807-12.
- Background: PubMed 17629517Butte MJ, Keir ME, Phamduy TB, Sharpe AH, Freeman GJ. Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity. 2007 Jul;27(1):111-22. doi: 10.1016/j.immuni.2007.05.016. Epub 2007 Jul 12.
- Background: PubMed 29270405Comunanza V, Bussolino F. Therapy for Cancer: Strategy of Combining Anti-Angiogenic and Target Therapies. Front Cell Dev Biol. 2017 Dec 7;5:101. doi: 10.3389/fcell.2017.00101. eCollection 2017.
- Background: PubMed 10678166Dong C, Li Z, Alvarez R Jr, Feng XH, Goldschmidt-Clermont PJ. Microtubule binding to Smads may regulate TGF beta activity. Mol Cell. 2000 Jan;5(1):27-34. doi: 10.1016/s1097-2765(00)80400-1.
- Background: PubMed 15032581Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Annu Rev Immunol. 2004;22:329-60. doi: 10.1146/annurev.immunol.22.012703.104803.
- Background: PubMed 18187370Ellis S, Carroll KJ, Pemberton K. Analysis of duration of response in oncology trials. Contemp Clin Trials. 2008 Jul;29(4):456-65. doi: 10.1016/j.cct.2007.10.008. Epub 2007 Nov 12.
- Background: PubMed 18759926Fife BT, Bluestone JA. Control of peripheral T-cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways. Immunol Rev. 2008 Aug;224:166-82. doi: 10.1111/j.1600-065X.2008.00662.x.
- Background: PubMed 15705911Hirano F, Kaneko K, Tamura H, Dong H, Wang S, Ichikawa M, Rietz C, Flies DB, Lau JS, Zhu G, Tamada K, Chen L. Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. Cancer Res. 2005 Feb 1;65(3):1089-96.
- Background: PubMed 14520469Hori K, Saito S. Microvascular mechanisms by which the combretastatin A-4 derivative AC7700 (AVE8062) induces tumour blood flow stasis. Br J Cancer. 2003 Oct 6;89(7):1334-44. doi: 10.1038/sj.bjc.6601261.
- Background: PubMed 12218188Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12293-7. doi: 10.1073/pnas.192461099. Epub 2002 Sep 6.
- Individual participant dataSharing planned: No
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Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingObservational study
Pre- and On-treatment Multi-omics Profiling of Locally Advanced Rectal Cancer
Rectal Neoplasms
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 2
Tislelizumab in People With Colorectal Cancer
Colorectal Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tea Won Kim principal investigator
Asan Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing CKD-516 plus Durvalumab in people with Colorectal Cancer and Solid Tumor, run by Tae Won Kim at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Recruitment difficulty). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04696848, which also lists 22 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2023.