Study of the Combination of DKN-01 and Nivolumab in Previously Treated Patients With Advanced Biliary Tract Cancer (BTC)

NCT04057365 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 19-200
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

This research is studying the effect of the combination of how two study drugs (Nivolumab and DKN-01) works in people with advanced biliary tract cancer.

Conditions

Biliary Tract Cancer

Keywords

Biliary Tract Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Overall response is evaluated using Response Evaluation Criteria in Solid Tumors criteria (RECIST 1.1). A participant is considered to have responded if they achieve either of the following outcomes: * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm * Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters

  up to 1 year

Secondary Outcomes (3)

• Progression Free Survival

  up to 1 year

• Overall Survival

  up to 1 year

• Treatment Emergent Adverse Events

  up to 1 year

Study Arms (2)

DKN 01 and Nivolumab Safety Run in

EXPERIMENTAL

* DKN-01 will be administered intravenously on day 1 and day 15 of each 28 day cycle * Nivolumab will be administered intravenously on day 1 and day 15 of each 28 day cycle

Drug: Nivolumab; Drug: DKN-01

DKN 01 and Nivolumab

EXPERIMENTAL

* DKN-01 will be administered intravenously on day 1 and day 15 of each 28 day cycle * Nivolumab will be administered intravenously on day 1 and day 15 of each 28 day cycle

Drug: Nivolumab; Drug: DKN-01

Interventions

Nivolumab DRUG

Nivolumab is believed to work by attaching to and inhibiting a specific protein in the cancer that controls parts of the immune system (the system in the body that fights off infections and diseases) by shutting down certain immune responses. The investigators believe that nivolumab will inhibit the protein, thus allowing the immune cells to recognize and destroy cancer cells.

Also known as: Opdivo

DKN 01 and Nivolumab; DKN 01 and Nivolumab Safety Run in

DKN-01 DRUG

DKN-01 is believed to work by attaching to and inhibiting (stopping) a specific pathway in the cells that is responsible for processes such as cell growth

DKN 01 and Nivolumab; DKN 01 and Nivolumab Safety Run in

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed intra- or extrahepatic cholangiocarcinoma or gallbladder cancer
• Participants must have measurable disease by CT/MRI by RECIST version 1.1 criteria
• Prior chemoembolization, radiofrequency ablation, or radiation to the liver is allowed as long as the patient has measurable disease outside of the treated area or measurable progression per RECIST v1.1 at the site of the treated area.
• Documented progression after ≥1 line of systemic therapy for advanced BTC. Prior adjuvant chemotherapy qualifies as this 1 line if the last cycle of adjuvant therapy was completed within 6 months of radiological progression.
• Age ≥ 18 years
• ECOG performance status ≤1
• Life expectancy of greater than 3 months
• Participants must have normal organ and marrow function as defined below:
• Absolute neutrophil count ≥1,500/mcL
• Absolute lymphocyte count ≥1.0 x 10\^9/L
• Platelets ≥75,000/mcL
• Hemoglobin ≥ 8.0 g/dL (prior transfusions are allowed if given ≥ 7 days before testing)
• Total bilirubin \< 2.0 x institutional upper limit of normal; except patients with Gilbert Syndrome who must have a total bilirubin level of \< 3.0 x ULN
• AST(SGOT)/ALT(SGPT) ≤3 × institutional upper limit of normal; \< 5 x ULN in case of liver metastases
• Creatinine \< 2.0 x institutional upper limit of normal OR Creatinine clearance ≥30 mL/min/1.73 m2 for participants with creatinine levels ≥ ULN

You may not qualify if:

• Prior DKK1 inhibitor or anti-PD-1/PD-L1 treatment
• Participants with Child-Pugh B or C cirrhosis
• Participants with a diagnosis of ampullary cancer
• Treatment with any of the following within the specified time frame prior to the first dose of DKN-01 and nivolumab:
• Any non-investigational or investigational anticancer therapy within 3 weeks or have not recovered from side effects of such therapy prior to treatment administration (mitomycin within prior 5 weeks). For targeted therapy, 5 half-lives are sufficient, even if \<3 weeks. Concurrent participation in an observational study may be allowed after review by the Principal Investigator.
• Patients with locoregional therapy, e.g., transarterial chemoembolization (TACE), selective internal radiotherapy (SIRT), external beam radiation, or ablation within 4 weeks
• Palliative limited field radiotherapy (i.e. bone metastases) within 2 weeks
• Major surgery within the previous 4 weeks (the surgical incision should be fully healed prior to the first dose of treatment)
• Fredericia's corrected QT interval (QTcF) ≥ 500 ms on ECG conducted during screening
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to DKN-01 or Nivolumab.
• A serious illness or medical condition(s) including, but not limited to, the following:
• Known brain metastasis (not including primary brain tumors) unless patient is clinically stable for ≥ 1 month without systemic corticosteroids beyond physiologic replacement (\>10 mg prednisone daily).
• Known acute systemic infection.
• Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure
• New York Heart Association \[NYHA\] Class III or IV (see Appendix D, New York Heart Association \[NYHA\] Classification) within the previous 2 months; if \>2 months, cardiac function must be within normal limits and the patient must be free of cardiac-related symptoms.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Bristol-Myers Squibb: collaborator
• Leap Therapeutics, Inc.: collaborator

Study Sites (2)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Joseph Franses, MD, PhD
• Organization: Massachusetts General Hospital

JFRANSES@MGH.HARVARD.EDU

617-724-4000

Study Officials

• Joseph Franses, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 13, 2019
• First Posted: August 15, 2019
• Study Start: October 7, 2019
• Primary Completion: September 25, 2022
• Study Completion: September 25, 2022
• Last Updated: August 13, 2025
• Results First Posted: April 10, 2024

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: MGH - Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (2)