Durvalumab and SNDX-6532 Following Chemo or Radio-Embolization for Patients With Intrahepatic Cholangiocarcinoma

Phase 2

Completed

Conditions: Unresectable Intrahepatic Cholangiocarcinoma

Interventions: Drug: Durvalumab
Drug: SNDX-6352

Registration Number: NCT04301778

Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 5

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Durvalumab and SNDX-6352	SNDX-6352	Participants will receive Durvalumab and SNDX-6352.
Durvalumab and SNDX-6352	Durvalumab	Participants will receive Durvalumab and SNDX-6352.

Primary Outcome Measures

Name	Time	Method
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.
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.

Secondary Outcome Measures

Name	Time	Method
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.