CA-4948 + Standard Therapy for Biliary Tract Cancer

Overseen By Olivia Aranha, M.D., Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Must not be taking: QTc prolonging drugs

Disqualifiers: Other malignancy, CNS metastasis, others

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

Compensation: Varies

Number of Visits: 63

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for advanced or metastatic biliary tract cancer, including gallbladder and certain liver cancers. Researchers aim to determine if adding CA-4948, an experimental drug, to standard chemotherapy and immunotherapy enhances treatment effectiveness by targeting cancer cell survival. Participants will take CA-4948 orally and receive other treatments intravenously in cycles. The trial seeks individuals who have not yet received treatment for their advanced biliary tract cancer and have a specific type of cancer called adenocarcinoma. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop your current medications, but you must be on a stable dose of any cholesterol-lowering statin for at least 3 weeks before starting the study. Also, you cannot use alternative or holistic treatments for cancer during the trial.

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

Research has shown that CA-4948 has a predictable and manageable safety profile based on previous studies. It has been tested in patients with conditions like acute myeloid leukemia and myelodysplastic syndromes, and results suggest it is generally well-tolerated. The dosage was safe up to 500 mg, indicating a good safety margin.

The other treatments in this trial—cisplatin, gemcitabine, and durvalumab—are already approved for use in other cancers, meaning they have known safety profiles. However, they can cause side effects. Cisplatin and gemcitabine, as chemotherapy drugs, can sometimes cause nausea or fatigue. Durvalumab, an immunotherapy, might lead to tiredness or cough.

Overall, the combination of these treatments is designed to be safe based on existing data. However, since this trial is in the early stages, monitoring participant responses remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatment combination of CA-4948 with gemcitabine, cisplatin, and durvalumab for biliary tract cancer because it introduces a novel component, CA-4948, which is not part of the current standard care. Most treatments for this condition, like gemcitabine and cisplatin, focus on traditional chemotherapy approaches. CA-4948 is unique because it is taken orally and acts as a targeted agent, which may enhance the effectiveness of the existing chemotherapy regimen. Additionally, the inclusion of durvalumab, an immunotherapy drug, aims to bolster the body's immune response against cancer cells, offering a multi-pronged attack on the disease. This combination could potentially improve outcomes and offer new hope for patients with this challenging type of cancer.

What evidence suggests that this trial's treatments could be effective for biliary tract cancer?

Studies have shown promising results for CA-4948 in treating certain cancers. In earlier research, patients with blood cancers such as AML (a type of leukemia) experienced significant improvements, with some achieving complete remission. CA-4948 blocks a protein called IRAK4, which aids cancer cell survival. This action might enhance the effectiveness of treatments like chemotherapy and immunotherapy. Although direct data for biliary tract cancer remains limited, early findings suggest CA-4948 could help by overcoming the tumor's defenses. In this trial, CA-4948 will be combined with standard treatments like gemcitabine, cisplatin, and durvalumab, with the expectation of improving patient outcomes. ^{4 5 6 7 8}

Who Is on the Research Team?

Olivia Aranha, M.D., Ph.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for individuals with advanced or metastatic biliary tract cancer who haven't been treated yet. Specific eligibility criteria are not provided, but typically participants would need to be adults with a confirmed diagnosis and meet certain health standards.

Inclusion Criteria

Measurable or evaluable disease defined by RECIST v1.1

My cancer can be biopsied for research, or the requirement has been waived.

I have been on the same dose of my cholesterol medication for at least 3 weeks.

Exclusion Criteria

I haven't taken steroids or immunosuppressants in the last 14 days, except for low-dose steroids.

I have had cancer before, but it's one of the exceptions.

I received chemoradiation less than 3 months ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Dose escalation of CA-4948 in combination with cisplatin, gemcitabine, and durvalumab to determine the expansion dose

Estimated 3-6 months

Visits every 21 days

Treatment

Participants receive CA-4948 in combination with cisplatin, gemcitabine, and durvalumab for up to 8 cycles

6 months

Visits every 21 days

Maintenance

Participants continue with CA-4948 and durvalumab as maintenance therapy after completing 8 cycles of cisplatin and gemcitabine

Estimated 8 months

Visits every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

38 months

What Are the Treatments Tested in This Trial?

Interventions

• CA-4948
• Cisplatin
• Durvalumab
• Gemcitabine

Trial Overview The study tests CA-4948 combined with standard chemotherapy drugs Cisplatin and Gemcitabine, plus the immunotherapy drug Durvalumab. It aims to see if this mix can improve treatment by targeting tumor survival signals and the immune-suppressive environment around tumors.

How Is the Trial Designed?

Group I: Dose Expansion: CA-4948 + Gemcitabine + Cisplatin + Durvalumab Experimental Treatment 4 Interventions

* Treatment will be administered on a 21-day cycle. * CA-4948 will be self-administered at the assigned dose by mouth twice per day at approximately 12-hour intervals. * Cisplatin and gemcitabine will be administered intravenously on Days 1 and 8 for up to 8 total cycles as per standard of care. Up to 2 cycles of gemcitabine and cisplatin, with or without durvalumab, may be given off protocol prior to enrollment; therefore some patients may receive only 6 or 7 cycles of gemcitabine, cisplatin, and durvalumab in combination with CA-4948 on study. Durvalumab will be administered IV on Day 1 of each cycle. Durvalumab will continue in combination with CA-4948 as maintenance therapy starting with Cycle 9 (or earlier, if patient discontinues cisplatin and gemcitabine prior to Cycle 9).

Group II: Dose Escalation Dose Level 0 (starting dose): CA-4948 + Gemcitabine + Cisplatin + Durvalumab Experimental Treatment 4 Interventions

* Treatment will be administered on a 21-day cycle. * CA-4948 will be self-administered at the assigned dose by mouth twice per day at approximately 12-hour intervals. * Cisplatin and gemcitabine will be administered intravenously on Days 1 and 8 for up to 8 total cycles as per standard of care. Up to 2 cycles of gemcitabine and cisplatin, with or without durvalumab, may be given off protocol prior to enrollment; therefore some patients may receive only 6 or 7 cycles of gemcitabine, cisplatin, and durvalumab in combination with CA-4948 on study. Durvalumab will be administered IV on Day 1 of each cycle. Durvalumab will continue in combination with CA-4948 as maintenance therapy starting with Cycle 9 (or earlier, if patient discontinues cisplatin and gemcitabine prior to Cycle 9).

Group III: Dose Escalation Dose Level -1: CA-4948 + Gemcitabine + Cisplatin + Durvalumab Experimental Treatment 4 Interventions

* Treatment will be administered on a 21-day cycle. * CA-4948 will be self-administered at the assigned dose by mouth twice per day at approximately 12-hour intervals. * Cisplatin and gemcitabine will be administered intravenously on Days 1 and 8 for up to 8 total cycles as per standard of care. Up to 2 cycles of gemcitabine and cisplatin, with or without durvalumab, may be given off protocol prior to enrollment; therefore some patients may receive only 6 or 7 cycles of gemcitabine, cisplatin, and durvalumab in combination with CA-4948 on study. Durvalumab will be administered IV on Day 1 of each cycle. Durvalumab will continue in combination with CA-4948 as maintenance therapy starting with Cycle 9 (or earlier, if patient discontinues cisplatin and gemcitabine prior to Cycle 9).

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Curis, Inc.

Industry Sponsor

Trials

17

Recruited

1,100+

Washington University Siteman Cancer Center

Collaborator

Trials

3

Recruited

90+

Citations

1. cancernetwork.com cancernetwork.com/view/ca-4948-yields-promising-clinical-activity-in-r-r-aml-mds-initial-findings-read-out-for-ci-8993-in-r-r-solid-tumors

CA-4948 Yields Promising Clinical Activity in R/R AML/MDS One patient achieved complete remission ,and 2 patients had 50% or higher reduction in blast counts. Reference. Curis announces updated data ...

2. delta.larvol.com delta.larvol.com/Products/?ProductId=e8437148-5f3b-46ca-a80c-8ea2df1c21e6

emavusertib (CA-4948) / Curis, Dr. Reddy's Clinical trial of an anti-cancer drug, CA-4948 (Emavusertib), in combination with chemotherapy treatment (FOLFOX Plus Bevacizumab) in metastatic colorectal ...

3. onclive.com onclive.com/view/irak-4-inhibitor-ca-4948-may-enhance-immunotherapeutic-outcomes-in-melanoma-with-brain-metastases

IRAK-4 Inhibitor CA-4948 May Enhance ... Promising preclinical findings have demonstrated that IRAK-4 is a viable target to increase the efficacy of immunotherapy in patients with ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06696768

NCT06696768 | Clinical Trial of an Anti-cancer Drug, CA ... Giving CA-4948 with FOLFOX plus bevacizumab may be safe, tolerable and/or effective in treating patients with metastatic colorectal cancer. Detailed Description.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10608206/

Targeted Therapies in Advanced Cholangiocarcinoma - PMC Primary tumor resection and liver transplantation are the only curative treatment options for the management of cholangiocarcinoma (CCA).

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07107750

CA-4948 in Combination With Cisplatin, Gemcitabine, and ... Therefore, this trial is designed to evaluate the combination of CA-4948 and standard chemoimmunotherapy in untreated advanced or metastatic ...

7. withpower.com withpower.com/trial/phase-1-biliary-tract-neoplasms-9-2025-cd07e

CA-4948 + Standard Therapy for Biliary Tract Cancer This trial is for individuals with advanced or metastatic biliary tract cancer who haven't been treated yet. Specific eligibility criteria are not provided, but ...

8. curis.com curis.com/wp-content/uploads/2021/08/CA-4948-Clinical-Study-in-AML-and-MDS.pdf

CA-4948-Clinical-Study-in-AML-and-MDS. ... CA-4948 in AML/MDS. 12. Preliminary safety data demonstrate safety and tolerability. Predictable and manageable safety profile. • MTD not exceeded until 500mg ...