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

27 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing XmAb20717, a drug that helps the immune system fight cancer, in patients with advanced biliary tract cancers. These patients have not responded to or cannot tolerate standard chemotherapy. The drug works by making the immune system better at finding and destroying cancer cells.

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.

What data supports the effectiveness of the drug XmAb20717 for treating biliary tract cancer?

Research shows that drugs targeting PD-1 and PD-L1, similar to XmAb20717, have shown a significant survival benefit when added to chemotherapy for advanced biliary tract cancer. Additionally, combining PD-1 inhibitors with other treatments has shown benefits in multiple solid tumors, suggesting potential effectiveness for XmAb20717. ^{1 2 3 4 5}

How is the drug XmAb20717 different from other treatments for biliary tract cancer?

XmAb20717 is unique because it is a bispecific antibody that targets both PD-1 and CTLA-4, which are proteins that help cancer cells evade the immune system. This dual targeting approach is different from other treatments that typically focus on just one of these proteins, potentially offering a more comprehensive immune response against the cancer. ^{1 2 3 4 6}

Research Team

Mark O'Hara, MD

Principal Investigator

Abramson Cancer Center at Penn Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Multicenter randomized phase II trial of atezolizumab with or without cobimetinib in biliary tract cancers. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Targeting PD-1/PD-L1 in biliary tract cancer: role and available data. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Clinical, Genomic, and Transcriptomic Data Profiling of Biliary Tract Cancer Reveals Subtype-Specific Immune Signatures. [2023]

4. United States 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. [2023]

5. New Zealand 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. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Phase 2 trial of bintrafusp alfa as second-line therapy for patients with locally advanced/metastatic biliary tract cancers. [2023]