Radiation + Immunotherapy for Bile Duct Cancer

Overseen By Eugene J. Koay

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immune checkpoint inhibitors, Systemic steroids

Disqualifiers: Pregnancy, Uncontrolled illness, Recent surgery, others

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

Compensation: Varies

Number of Visits: 27

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for advanced bile duct cancer that has spread, using radiation and an experimental drug called bintrafusp alfa (an immunotherapy). The goal is to determine the optimal dose, benefits, and any side effects. The treatment involves administering higher radiation doses over a shorter period and using bintrafusp alfa to enhance the immune system's response to cancer. Patients with bile duct cancer who have previously undergone chemotherapy or opted against it, and have at least two measurable tumors, might be suitable candidates. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering patients the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on certain immune-based treatments or high doses of steroids. If you have taken any anticancer medication recently, you may need to wait before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that bintrafusp alfa remains safe for long-term use. In a study involving patients with biliary tract cancer, it provided lasting benefits without introducing new safety concerns. Some side effects occurred but were manageable.

Studies indicate that hypofractionated radiation therapy is generally well-tolerated. In one study, only 24% of patients experienced significant treatment-related side effects. This therapy uses higher doses over a shorter period, which can effectively treat liver cancers.

Overall, both treatments undergo careful safety testing. Previous studies suggest they are generally well-tolerated, though individual experiences may vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for bile duct cancer because it combines bintrafusp alfa with hypofractionated radiation therapy in a novel way. Bintrafusp alfa is a unique fusion protein that targets both TGF-β and PD-L1, potentially enhancing the immune system's ability to fight cancer. Unlike traditional treatments that focus solely on chemotherapy or standard radiation, this approach uses a focused, higher-dose radiation schedule alongside an innovative immunotherapy agent. This combination could offer a more effective response by not just attacking the tumor directly but also by rallying the body's own defenses against the cancer.

What evidence suggests that this trial's treatments could be effective for bile duct cancer?

This trial will evaluate the combination of hypofractionated radiation therapy and bintrafusp alfa for bile duct cancer. Studies have shown that hypofractionated radiation therapy can effectively control tumors, achieving up to 85% local control in bile duct cancers. This type of radiation delivers higher doses over a shorter period, potentially killing tumor cells more effectively and with fewer side effects. Research indicates that bintrafusp alfa has shown some effectiveness in treating bile duct cancer by helping the immune system target cancer cells. Although its benefits have been modest, previous studies have demonstrated its potential for improving survival. Combining these treatments in this trial may offer a more comprehensive approach to controlling bile duct cancer. ^{1 3 6 7 8}

Who Is on the Research Team?

Eugene J. Koay

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced bile duct cancer who have tried at least one chemotherapy or refused it. They must have two measurable tumors, be in good physical condition, and agree to use birth control. People can't join if they have autoimmune diseases, recent infections requiring antibiotics, major surgery within 4 weeks, received certain treatments recently, untreated brain metastases, are pregnant or breastfeeding.

Inclusion Criteria

Total bilirubin < 1.5 x institutional upper limit of normal (IULN)

I am fully active or have minor restrictions in physical activity.

I have undergone or refused initial chemotherapy.

Exclusion Criteria

Patients who are pregnant or lactating

I have not had major bleeding in the last 4 weeks.

I haven't taken cancer drugs in the last 21 days and don't have major side effects from past treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Therapy

Patients undergo hypofractionated radiation therapy once daily on weekdays for 15 fractions

3 weeks

15 visits (in-person)

Treatment with Bintrafusp Alfa

Patients receive bintrafusp alfa intravenously over 1 hour on day 1, with cycles repeating every 14 days for up to 2 years

Up to 2 years

Bi-weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Every 12 weeks (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Bintrafusp Alfa
• Hypofractionated Radiation Therapy

Trial Overview

The trial tests a combination of hypofractionated radiation therapy (higher doses over a short period) and bintrafusp alfa (an immunotherapy drug). It aims to find the best dose and see how well this combo works against advanced intrahepatic cholangiocarcinoma by helping the immune system attack cancer.

How Is the Trial Designed?

Group I: Treatment (hypofractionated radiation, bintrafusp alfa) Experimental Treatment 3 Interventions

Patients undergo hypofractionated radiation therapy QD on weekdays (Monday-Friday) for 15 fractions in the absence of disease progression or unacceptable toxicity. Beginning 1 week after completion of radiation therapy, patients receive bintrafusp alfa IV over 1 hour on day 1. Cycles repeat every 14 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Bintrafusp Alfa is already approved in United States, European Union for the following indications:

Approved in United States as Bintrafusp Alfa for:

• Non-small cell lung cancer (NSCLC)

Approved in European Union as Bintrafusp Alfa for:

• Biliary tract cancer

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

In a phase II study involving 111 high-risk prostate cancer patients, hypofractionated radiation therapy (HFRT) was found to be well tolerated, with no significant difference in acute gastrointestinal (GI) or genitourinary (GU) toxicity compared to conventionally fractionated radiation therapy (CFRT).

Both HFRT and CFRT resulted in similar 3-year biochemical recurrence-free survival rates (97.3% for HFRT vs 91.0% for CFRT) and overall survival rates (94.8% for HFRT vs 100.0% for CFRT), indicating that HFRT is a safe and effective treatment option for high-risk prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Outcomes of the CHIRP Trial: A Phase II Prospective Randomized Trial of Conventionally Fractionated Versus Moderately Hypofractionated Prostate and Pelvic Nodal Radiation Therapy in Patients With High-Risk Prostate Cancer. Wang, MH., Vos, LJ., Yee, D., et al.[2021]

The study demonstrated that hypofractionated, conformal radiation therapy (RT) at a dose of 50 Gy in 10 fractions is feasible and safe for treating patients with liver metastases, with no dose-limiting toxicities observed across all dose levels in a cohort of 26 patients.

While some patients experienced grade 3 toxicities, such as enteritis and lymphopenia, these were manageable and reversible, indicating that higher doses of radiation can be administered safely in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NRG Oncology/RTOG 0438: A Phase 1 Trial of Highly Conformal Radiation Therapy for Liver Metastases. Dawson, LA., Winter, KA., Katz, AW., et al.[2020]

The FORCE study is a phase II trial involving 130 patients with stage IV non-squamous non-small cell lung cancer, investigating the effects of nivolumab combined with hypofractionated palliative radiotherapy, aiming to assess its safety and efficacy in improving response rates and survival outcomes.

Preliminary data suggest that combining nivolumab with radiation therapy may enhance immune responses against tumors, potentially leading to better treatment outcomes compared to nivolumab alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fostering efficacy of anti-PD-1-treatment: Nivolumab plus radiotherapy in advanced non-small cell lung cancer - study protocol of the FORCE trial. Bozorgmehr, F., Hommertgen, A., Krisam, J., et al.[2020]

Citations

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ascopubs.org

ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e16077

Efficacy of bintrafusp alfa (M7824) in patients with ...

Conclusions: Bintrafusp Alfa demonstrated modest efficacy in gastrointestinal tumors and limited survival benefits (PFS: 1.496 months; OS: 8.969 ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10442127/

Phase 2 trial of bintrafusp alfa as second-line therapy for ...

At the data cutoff of March 30, 2021, the median follow-up time was 16.1 months (range, 0.0–19.3 mo); 3 patients remained on treatment (1.9%). The most common ...

3.

emdserono.com

emdserono.com/us-en/company/news/press-releases/topline-data-for-bintrafusp-alfa-as-second-line-monotherapy-treatment-in-biliary-tract-cancer-16-03-2021.html

Topline Data for Bintrafusp Alfa as Second-Line ...

In the study of 159 patients, bintrafusp alfa demonstrated single-agent efficacy and durability with a manageable safety profile after more than ...

4.

journals.lww.com

journals.lww.com/hep/fulltext/2025/03000/bintrafusp_alfa_and_chemotherapy_as_first_line.14.aspx

Bintrafusp alfa and chemotherapy as first-line treatment in .. ...

The median follow-up duration for OS was 8.4 months (range: 0.2–13.9) and 7.6 months (range: 0.9–15.2) in the bintrafusp alfa and placebo groups, respectively.

5.

onclive.com

onclive.com/view/bintrafusp-alfa-monotherapy-showcases-efficacy-durability-in-second-line-biliary-tract-cancer

Bintrafusp Alfa Monotherapy Showcases Efficacy, ...

Single-agent bintrafusp alfa demonstrated efficacy, durability, and an acceptable toxicity profile when used in patients with locally advanced ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6421170/

AB052. P-20. Phase 2, open-label study of second-line ...

In an expansion cohort of study NCT02699515 of 30 patients with pretreated advanced BTC, M7824 monotherapy demonstrated a 23.3% confirmed ORR by investigator ...

7.

sciencedirect.com

sciencedirect.com/science/article/pii/S0169500225004374

Efficacy and safety of bintrafusp alfa evaluated in a phase II ...

Bintrafusp alfa did not reach the expected efficacy in patients with advanced PM. We did not identify new safety signals with bintrafusp alfa, and no case of ...

8.

annalsofoncology.org

annalsofoncology.org/article/S0923-7534(20)40047-X/fulltext

73P Long-term follow-up of bintrafusp alfa, a bifunctional ...

After 28 months, bintrafusp alfa continues to demonstrate manageable safety with durable responses and long-term survival in Asian patients with pretreated BTC.