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

• ClinicalTrials.gov Identifier: NCT04301778
• Recruitment Status: Active, not recruiting
• First Posted: March 10, 2020
• Results First Posted: March 31, 2023
• Last Update Posted: March 31, 2023
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Syndax Pharmaceuticals; AstraZeneca
• Information provided by (Responsible Party): Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Tracking Information

• First Submitted Date: March 6, 2020
• First Posted Date: March 10, 2020
• Results First Submitted Date: March 6, 2023
• Results First Posted Date: March 31, 2023
• Last Update Posted Date: March 31, 2023
• Actual Study Start Date: August 24, 2021
• Actual Primary Completion Date: November 4, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 6, 2023)

• Objective Response Rate (ORR) Per mRECIST (Modified RECIST) [ Time Frame: 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 [ Time Frame: up to 1 year ]
  Number of participants who experience treatment related adverse events ≥ grade 3 as defined by CTCAE 5.0.

Original Primary Outcome Measures (submitted: March 6, 2020)

• Objective Response Rate (ORR) per mRECIST (modified RECIST) [ Time Frame: 4 years ]
  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 [ Time Frame: 4 years ]
  When calculating the incidence of Adverse Events (AEs), each AE (as defined by NCI CTCAE v5.0) will be counted only once for a given subject.

Current Secondary Outcome Measures (submitted: March 6, 2023)

• Overall Survival (OS) [ Time Frame: 4 years ]
  OS will be measured from date of first dose until death or end of followup (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.
• Progression-free Survival (PFS) Per mRECIST [ Time Frame: 4 years ]
  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) [ Time Frame: 4 years ]
  Number of weeks from the start date of PR or CR (whichever response is recorded first) and subsequently confirmed to the first date that recurrent or 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.

Original Secondary Outcome Measures (submitted: March 6, 2020)

• Overall survival (OS) [ Time Frame: 4 years ]
  OS will be measured from date of first dose until death or end of followup (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.
• Progression-free Survival (PFS) per mRECIST [ Time Frame: 4 years ]
  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) [ Time Frame: 4 years ]
  Number of weeks from the start date of PR or CR (whichever response is recorded first) and subsequently confirmed to the first date that recurrent or 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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Durvalumab and SNDX-6532 Following Chemo or Radio-Embolization for Patients With Intrahepatic Cholangiocarcinoma
• Official Title: A Phase II Study of Durvalumab (MEDI4736) in Combination With a CSF-1R Inhibitor (SNDX-6532) Following Chemo or Radio-Embolization for Patients With Intrahepatic Cholangiocarcinoma.
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Unresectable Intrahepatic Cholangiocarcinoma

Intervention

• Drug: Durvalumab
  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
  Other Name: MEDI4736
• Drug: SNDX-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
  Other Name: UCB6352

Study Arms

Experimental: Durvalumab and SNDX-6352

Participants will receive Durvalumab and SNDX-6352.

Interventions:

• Drug: Durvalumab
• Drug: SNDX-6352

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: November 10, 2022): 5
• Original Estimated Enrollment (submitted: March 6, 2020): 30
• Estimated Study Completion Date: September 1, 2025
• Actual Primary Completion Date: November 4, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04301778
• Other Study ID Numbers: J2031; IRB00233351 ( Other Identifier: Johns Hopkins Institutional Review Board )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Original Responsible Party: Same as current
• Current Study Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Original Study Sponsor: Same as current

Collaborators

• Syndax Pharmaceuticals
• AstraZeneca

Investigators

• Principal Investigator: Lei Zheng, MD; Sidney Kimmel Cancer Center at the Johns Hopkins Medical Institution

• PRS Account: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Verification Date: March 2023