XmAb20717 in Advanced Biliary Tract Cancers

• ClinicalTrials.gov Identifier: NCT05297903
• Recruitment Status: Recruiting
• First Posted: March 28, 2022
• Last Update Posted: November 21, 2022
• Sponsor: Abramson Cancer Center of the University of Pennsylvania
• Collaborator: Xencor, Inc.
• Information provided by (Responsible Party): Abramson Cancer Center of the University of Pennsylvania

Study Description

Brief Summary:

This is a single-arm, phase II clinical trial to evaluate the efficacy of XmAb20717 in patients with advanced biliary tract cancers who have progressed on, or were intolerant of, a gemcitabine-based chemotherapy regimen.

Condition or disease	Intervention/treatment	Phase
Biliary Tract Cancer	Drug: XmAb20717	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 27 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of XmAb20717 in Patients With Advanced Biliary Tract Cancers
• Actual Study Start Date: April 11, 2022
• Estimated Primary Completion Date: March 31, 2024
• Estimated Study Completion Date: December 31, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: XmAb20717; Study participants will receive the recommended phase II dose (10mg/kg) of XmAb20717 by intravenous infusion on days 1 and 15 of a 28-day cycle for up to 2 years.	Drug: XmAb20717; 10mg/kg IV; Other Name: ANTI-PD1 × ANTI-CTLA4 BISPECIFIC MONOCLONAL ANTIBODY

Outcome Measures

Primary Outcome Measures :

1. Objective Response Rate (ORR) [ Time Frame: From therapy initiation, assessed at each restaging scan, for up to 24 months ]
   Proportion of participants with the best response being complete response (CR) or partial response (PR)

Secondary Outcome Measures :

1. Progression-free survival [ Time Frame: From therapy initiation until progression or death, whichever comes first, for up to 60 months ]
   Time from study enrollment until disease progression or death with censoring for loss to follow up
2. Overall survival [ Time Frame: From therapy initiation until death, for up to 60 months ]
   Time from study enrollment until death

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Patient must have advanced biliary tract cancers (BTC) including intrahepatic, perihepatic, or extrahepatic cholangiocarcinoma or gallbladder carcinoma with histologic or cytologic confirmation who have experienced progression, or intolerance of, systemic therapy with a gemcitabine-based regimen.
2. Patients with tumors harboring an FGFR2 fusion, NTRK fusion, or IDH1 mutation must have received molecularly targeted therapy unless contraindicated or refused.
3. ECOG performance status of 0 or 1.
4. Measurable or evaluable disease as defined by RECIST v. 1.1.
5. Available archival tissue or willingness to undergo biopsy during the screening period; this requirement can be waived if biopsy deemed infeasible or unsafe by the principal investigator.
6. Must have adequate organ and hematopoietic function within 14 days of the start of study treatment.

Exclusion Criteria:

1. Any concurrent condition requiring the continued or anticipated use of systemic steroids beyond physiologic replacement dosing (excluding non-systemic inhaled, topical skin, nasal, and/or ophthalmic corticosteroids). All other systemic corticosteroids above physiologic replacement dosing must be discontinued at least four weeks prior to first study treatment.
2. Treatment with another investigational drug or other intervention within four weeks prior to the first study treatment date.
3. Treatment with trans-arterial liver embolization, hepatic arterial infusion, or radiation doses of > 30 Gy within 4 weeks prior to the first study treatment date
4. Treatment with chemotherapy within 3 weeks prior to the first study treatment date
5. Prior treatment with a PD-1 inhibitor, PD-L1 inhibitor, or CTLA-4 inhibitor
6. Known allergic reactions to study drug components.
7. Active brain metastases. Patients with brain metastases must have stable neurological status following local therapy (surgery or radiation) for at least four weeks prior to first study treatment and must be off steroids related to the brain metastases for at least two weeks prior to study treatment.
8. Active drug or alcohol use or dependence as documented in the chart that, in the opinion of the investigator, would interfere with adherence to study requirements.
9. Active bacterial, viral, parasitic, or fungal infection requiring IV therapy within 2 weeks of the start of protocol treatment.
10. A secondary primary malignancy that, in the judgment of the investigator, may affect the interpretation of results.
11. Prior organ allograft or allogeneic bone marrow transplantation.
12. A history of, or active, pneumonitis or interstitial lung disease.
13. Active autoimmune disease. Patients with vitiligo, type 1 diabetes mellitus, endocrinopathies manageable by hormone replacement, and psoriasis not requiring systemic treatment are permitted to enroll. Other autoimmune conditions may be allowable at the discretion of the principal investigator.

Contacts and Locations

Contacts

Contact: Jennifer Walsh; 609-668-0689; Jennifer.Walsh4@pennmedicine.upenn.edu

Contact: Thomas Karasic, MD; 215-614-1858; Thomas.Karasic@pennmedicine.upenn.edu

Locations

United States, Pennsylvania

Abramson Cancer Center at University of Pennsylvania; Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contact: Jennifer Walsh 609-668-0689 Jennifer.Walsh4@pennmedicine.upenn.edu

Contact: Thomas Karasic, MD 215-614-1858 Thomas.Karasic@pennmedicine.upenn.edu

Sponsors and Collaborators

Abramson Cancer Center of the University of Pennsylvania

Xencor, Inc.

Investigators

• Principal Investigator: Thomas Karasic, MD; Abramson Cancer Center of the University of Pennsylvania

More Information

• Responsible Party: Abramson Cancer Center of the University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT05297903
• Other Study ID Numbers: UPCC 17221; IRB#850515 ( Other Identifier: University of Pennsylvania IRB )
• First Posted: March 28, 2022
• Last Update Posted: November 21, 2022
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Additional relevant MeSH terms:

Biliary Tract Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Antibodies, Bispecific; Immunologic Factors; Physiological Effects of Drugs