XmAb20717 for Biliary Tract Cancer

Overseen By Thomas Karasic, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Abramson Cancer Center of the University of Pennsylvania

Must not be taking: Systemic steroids, CTLA-4 inhibitors

Disqualifiers: Pregnancy, Active brain metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, XmAb20717 (a bispecific antibody), for people with advanced biliary tract cancer. Researchers aim to evaluate its effectiveness in those who have not responded to prior gemcitabine-based chemotherapy. Participants will receive the treatment through an IV on specific days within a 28-day cycle. Ideal candidates are those with advanced biliary tract cancer who have either not succeeded with gemcitabine chemotherapy or cannot tolerate it. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking systemic steroids above physiologic replacement dosing at least four weeks before starting the study treatment. Other medications, like chemotherapy, must be stopped three weeks prior. The protocol does not specify other medications, so it's best to discuss your current medications with the study team.

Is there any evidence suggesting that XmAb20717 is likely to be safe for humans?

Research has shown that XmAb20717, a special type of antibody, holds promise. This antibody targets two proteins, PD-1 and CTLA-4, which help cancer cells evade the immune system. The treatment aids the immune system in recognizing and attacking cancer cells.

In earlier studies with patients who had advanced solid tumors, XmAb20717 was generally well-tolerated. About 19% of patients responded positively to the treatment at the recommended dose. While some side effects occurred, most participants found them manageable.

Since this trial is in the second phase, XmAb20717 has already passed initial safety tests. This phase focuses more on the treatment's effectiveness while still monitoring safety. This indicates that XmAb20717 is considered safe enough for testing on a larger group of people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for biliary tract cancer, which typically include chemotherapy and targeted therapies like gemcitabine and cisplatin, XmAb20717 is unique because it is a bispecific antibody. It targets two checkpoints, PD-1 and CTLA-4, which are proteins that help cancer cells evade the immune system. By blocking these checkpoints, XmAb20717 can potentially enhance the immune system's ability to detect and destroy cancer cells. Researchers are excited about this treatment because it offers a novel approach to boosting the body's natural defenses against cancer, potentially leading to better outcomes for patients.

What evidence suggests that XmAb20717 might be an effective treatment for biliary tract cancer?

Research has shown that XmAb20717, the investigational treatment in this trial, could be a promising option for advanced biliary tract cancer. This treatment uses a specially designed antibody to target two proteins, PD-1 and CTLA-4, which often help cancer evade the immune system. By blocking these proteins, XmAb20717 enables the immune system to find and fight cancer cells more effectively. In earlier studies, XmAb20717 led to a 19% response rate in patients with advanced solid tumors, meaning some tumors shrank. Although more research is needed, these early results suggest XmAb20717 could benefit biliary tract cancer patients who haven't responded to standard chemotherapy. ^{1 2 3 4 5}

Who Is on the Research Team?

Mark O'Hara, MD

Principal Investigator

Abramson Cancer Center at Penn Medicine

Are You a Good Fit for This Trial?

Adults over 18 with advanced biliary tract cancers, who've had progression or intolerance to gemcitabine-based therapy. They must be in relatively good health (ECOG status of 0 or 1), have measurable disease, and agree to contraception if of reproductive potential. Exclusions include recent use of certain cancer treatments, history of severe reactions to PD-1/PD-L1 inhibitors or CTLA-4 inhibitors, active infections requiring IV treatment, other serious medical conditions, and known HIV infection not well-controlled.

Inclusion Criteria

For females of reproductive potential: Must have a negative serum pregnancy test performed within 7 days of first study treatment and must agree to use such a method during study participation and for an additional 3 months after the last study dose of XmAb20717. Reproductive potential is defined in section 8.2.11

I can provide tissue samples or am willing to have a biopsy if it's safe.

I have or haven't been treated for specific genetic changes in my tumor if they were found.

Exclusion Criteria

My brain cancer has not worsened for 4 weeks after treatment, and I haven't taken steroids for it in 2 weeks.

I haven't had serious infections needing IV treatment in the last 2 weeks.

I have had or currently have lung inflammation or scarring.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive XmAb20717 by intravenous infusion on days 1 and 15 of a 28-day cycle for up to 2 years

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• XmAb20717

Trial Overview The trial is testing XmAb20717 for patients with advanced biliary tract cancers who haven't responded well to previous chemotherapy. It's a phase II study where all participants receive the same experimental drug without being compared to another treatment.

How Is the Trial Designed?

Group I: XmAb20717 Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Abramson Cancer Center of the University of Pennsylvania

Lead Sponsor

Trials

360

Recruited

108,000+

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

Xencor, Inc.

Industry Sponsor

Trials

31

Recruited

2,500+

Published Research Related to This Trial

In a phase II study involving 77 patients with unresectable biliary tract cancers, the combination of atezolizumab (anti-PD-L1) and cobimetinib (MEK inhibitor) significantly improved progression-free survival (PFS) to a median of 3.65 months compared to 1.87 months for atezolizumab alone.

Despite the improved PFS, the overall response rates were low in both treatment groups, indicating that biliary tract cancers may be resistant to immune therapies, and combination therapy was associated with increased side effects such as rash and gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter randomized phase II trial of atezolizumab with or without cobimetinib in biliary tract cancers. Yarchoan, M., Cope, L., Ruggieri, AN., et al.[2023]

In a phase 2 trial involving 75 patients with advanced biliary tract cancer, the combination of nivolumab with gemcitabine and cisplatin (Arm A) resulted in a significantly higher 6-month progression-free survival (PFS) rate of 59.4% compared to 21.2% in the group receiving nivolumab and ipilimumab (Arm B).

While the overall survival (OS) was less than 12 months for both treatment arms, Arm A showed a promising 2-year OS rate, indicating potential long-term benefits for some patients despite the overall limited efficacy of the treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase 2 trial of nivolumab, gemcitabine, and cisplatin or nivolumab and ipilimumab in previously untreated advanced biliary cancer: BilT-01. Sahai, V., Griffith, KA., Beg, MS., et al.[2023]

In a study of 210 patients with advanced biliary tract carcinoma, PD-1 monoclonal antibody (PD-1-mAb) combination therapy significantly improved median progression-free survival (mPFS) and median overall survival (mOS) compared to standard chemotherapy in both first-line and second-line treatments.

Specifically, the first-line PD-1-mAb combination group had a mPFS of 7.3 months and mOS of 15.6 months, while the second-line group had a mPFS of 6.1 months and mOS of 11.7 months, indicating that PD-1-mAb combinations are promising treatment options for this challenging cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1-mAb Plus Regimen in the First and Second Lines of Advanced and Unresectable Biliary Tract Carcinoma: A Real-World, Multicenter Retrospective Analysis. Wang, F., Wang, FH., Sun, K., et al.[2022]

Citations

1. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/03/NCT05297903/Prot_SAP_001.pdf

Protocol Title: Phase II trial of XmAb20717 in patients with ... XmAb20717 is a humanized bispecific antibody that binds the immune checkpoint molecules PD-1 and CTLA4 in order to block signaling that prevents ...

2. investors.xencor.com investors.xencor.com/news-releases/news-release-details/xencor-presents-updated-data-phase-1-study-vudalimab-pd-1-x-ctla

Xencor Presents Updated Data from the Phase 1 Study of ... Data from its Phase 1 study evaluating vudalimab (XmAb 717), a PD-1 x CTLA-4 bispecific antibody, in patients with advanced solid tumors (DUET-2).

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05733351

Vudalimab (XmAb20717) in Combination With Standard of ... This phase I trial tests the safety and effectiveness of vudalimab (XmAb20717) in combination with standard of care treatment abiraterone, enzalutamide, ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT364418

A phase 2, multicenter, parallel-group, open-label study of ... Vudalimab (XmAb20717) is a humanized bispecific monoclonal antibody that simultaneously targets PD-1 and CTLA-4 and binds preferentially to PD-1/CTLA-4 dual ...

5. investors.xencor.com investors.xencor.com/news-releases/news-release-details/xencor-presents-updated-data-duet-2-phase-1-study-xmab20717-pd-1

Xencor Presents Updated Data From the DUET-2 Phase 1 ... XmAb20717 was generally well-tolerated; 19% objective response rate (ORR) observed across cohorts at the recommended dose level.