Unresectable Intrahepatic Cholangiocarcinoma
Conditions
Keywords
colony stimulating factor -1 receptor (CSF-1R) inhibitor, Anti-PD-1 (receptor blocking antibody), Immunotherapy, Intra-arterial therapy, Y90 (yttrium-90 radioembolization), conventional transarterial chemoembolization (cTACE), Chemo-embolization, Radio-embolization, Biliary tract, Intrahepatic Cholangiocarcinoma, Monoclonal antibody
Brief summary
The purposed of this research is to study the safety and clinical activity of the combination of durvalumab and a CSF-1R inhibitor (SNDX-6352) in people with Intrahepatic Cholangiocarcinoma.
Interventions
DRUGDurvalumab
1. Durvalumab - 1500 mg via IV infusion over 60 minutes (-5/+10 min) on day 1 of each 28-day cycle (every 4 weeks). 2. Drug - 1500mg IV
DRUGSNDX-6352
1. SNDX-6352 - 3mg/kg via IV infusion over 30 minutes (-5/+10 min) on days 1 and 15 of each 28-day cycle (every 2 weeks), starting with cycle 2 (not given during cycle 1). 2. Drug - 3mg/kg IV
Sponsors
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Syndax Pharmaceuticals
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have cytologically confirmed intrahepatic cholangiocarcinoma. * All disease must be localized to the liver (locally advanced). * Subjects must not be deemed surgical candidates. * Must be a candidate for conventional transarterial chemoembolization or yttrium-90 radioembolization. * Must have measureable disease be mRECIST. Measurable disease will be confirmed by radiological imaging (MRI, CT). * Age ≥18 years * Body weight \> 30 kg * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Life expectancy ≥12 weeks. * Patient must have adequate organ function defined by the study-specified laboratory tests as per the protocol. * Child Pugh Class A * Measured creatinine clearance (CL) \>40 mL/min or Calculated creatinine clearance CL\>40 mL/min by the Cockcroft-Gault formula. * Woman of childbearing potential must have a negative pregnancy test and follow contraceptive guidelines as defined per protocol. * Must use acceptable form of birth control while on study. * Men must use acceptable form of birth control while on study. * Ability to understand and willingness to sign a written informed consent document. * Willing and able to comply with the protocol for the duration of the study
Exclusion criteria
* Candidate for surgical resection * Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up of an interventional study. * Major surgery within 4 weeks prior to initiation of study treatment. * Received the last dose of anticancer therapy ≤ 28 days prior to the first dose of study drug. * All toxicities NCI CTCAE Grade ≥2 attributed to prior anti-cancer therapy other than alopecia, vitiligo, and neuropathy. * Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. * 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, checkpoint inhibitor-induced immune mediated reaction or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]). * Patient with uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, significant muscle disorders or psychiatric illness/social situations that would limit compliance with study requirements. * History of known additional primary malignancies. * History of leptomeningeal carcinomatosis. * Brain metastases or spinal cord compression. * History of active primary immunodeficiency. * Infection with Tuberculosis, HIV or hepatitis B or C at screening. * Current or prior use of immunosuppressive medication within 14 days before the first dose of treatment. * Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. * Pregnant or breastfeeding women. * Has a history of allergy to study treatments or any of its components of the study. * Prior randomization or treatment in a previous durvalumab and/or SNDX-6532 clinical study regardless of treatment arm assignment. * Patient has clinically significant heart disease. * Any other sound medical, psychiatric, and/or social reason as determined by the Investigator. * Unwilling or unable to follow the study schedule for any reason.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Per mRECIST (Modified RECIST) | 8 months | ORR is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (mRECIST) at any time during the study. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve. |
| Number of Participants Experiencing Study Drug-related Toxicities | up to 1 year | Number of participants who experience treatment related adverse events ≥ grade 3 as defined by CTCAE 5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | up to 2 years | OS is defined as the number of months from the start of study treatment to time of death. Individuals are censored at the date of the last contact if no event occurs. The estimation method used was Kaplan-Meier. |
| Progression-free Survival (PFS) Per mRECIST | 8 months | PFS is defined as the number of months from the date of treatment to disease recurrence \[disease recurrence (DR) progressive disease (PD) or relapse from complete response (CR) as assessed using mRECIST criteria\] or death due to any cause. Per mRECIST criteria, CR = disappearance of all target lesions, Partial Response (PR) is =\>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is \>20% increase in sum of diameters of target lesions, Stable Disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. |
| Duration of Response (DOR) | 8 months | Number of days from the start of partial response (PR) or complete response (CR) by radiographic scans, whichever is recorded first, until the first date that progressive disease or death is documented. Per mRECIST, CR = disappearance of any intratumoral arterial enhancement in all target lesions, PR is =\>30% decrease in sum of diameters of target lesions. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORLei Zheng, MD
Sidney Kimmel Cancer Center at the Johns Hopkins Medical Institution
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Durvalumab and SNDX-6352 Participants received Durvalumab and SNDX-6352.
Durvalumab: 1500 mg IV over 60 minutes on day 1 of each 28-day cycle (every 4 weeks).
SNDX-6352: 3mg/kg IV over 30 minutes on days 1 and 15 of each 28-day cycle (every 2 weeks), starting with cycle 2 (not given during cycle 1). | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | Durvalumab and SNDX-6352 |
|---|---|
| Age, Continuous | 60 years |
| Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG 0 | 4 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG 1 | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Region of Enrollment United States | 5 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 5 |
| other Total, other adverse events | 5 / 5 |
| serious Total, serious adverse events | 1 / 5 |
Outcome results
Primary
Number of Participants Experiencing Study Drug-related Toxicities
Number of participants who experience treatment related adverse events ≥ grade 3 as defined by CTCAE 5.0.
Time frame: up to 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Durvalumab and SNDX-6352 | Number of Participants Experiencing Study Drug-related Toxicities | 2 Participants |
Primary
Objective Response Rate (ORR) Per mRECIST (Modified RECIST)
ORR is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (mRECIST) at any time during the study. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve.
Time frame: 8 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Durvalumab and SNDX-6352 | Objective Response Rate (ORR) Per mRECIST (Modified RECIST) | 1 Participants |
Secondary
Duration of Response (DOR)
Number of days from the start of partial response (PR) or complete response (CR) by radiographic scans, whichever is recorded first, until the first date that progressive disease or death is documented. Per mRECIST, CR = disappearance of any intratumoral arterial enhancement in all target lesions, PR is =\>30% decrease in sum of diameters of target lesions.
Time frame: 8 months
Population: Only patients with either a partial or complete response by mRECIST are included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Durvalumab and SNDX-6352 | Duration of Response (DOR) | 57 days |
Secondary
Overall Survival (OS)
OS is defined as the number of months from the start of study treatment to time of death. Individuals are censored at the date of the last contact if no event occurs. The estimation method used was Kaplan-Meier.
Time frame: up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab and SNDX-6352 | Overall Survival (OS) | 15.3 months |
Secondary
Progression-free Survival (PFS) Per mRECIST
PFS is defined as the number of months from the date of treatment to disease recurrence \[disease recurrence (DR) progressive disease (PD) or relapse from complete response (CR) as assessed using mRECIST criteria\] or death due to any cause. Per mRECIST criteria, CR = disappearance of all target lesions, Partial Response (PR) is =\>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is \>20% increase in sum of diameters of target lesions, Stable Disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions.
Time frame: 8 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab and SNDX-6352 | Progression-free Survival (PFS) Per mRECIST | 3.6 months |