AL101 Before Surgery for Adenoid Cystic Carcinoma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Gamma-secretase inhibitors

Disqualifiers: Uncontrolled infection, CNS metastases, others

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

Compensation: Varies

Number of Visits: 6

Duration: 6-8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how well a new drug, AL101, can manage adenoid cystic carcinoma before surgery. The focus is on understanding the side effects and potential benefits of AL101, which might block enzymes that promote tumor growth, particularly in cancers with an activated pathway called NOTCH. Suitable candidates for this trial have adenoid cystic carcinoma that can be surgically removed and show activation of the NOTCH1 pathway in their cancer cells. As a Phase 1 trial, this research aims to understand 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 to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that AL101 is likely to be safe for humans?

Research has shown that AL101 is generally safe and well-tolerated in patients with adenoid cystic carcinoma (ACC) who have a mutation in the NOTCH pathway. In earlier studies, 71% of patients had their disease controlled at a specific dose, indicating that the treatment can effectively manage the cancer without causing serious harm.

While side effects can occur, the overall safety of AL101 is comparable to other treatments for this condition, meaning it doesn't cause more side effects than patients might expect from other therapies.

AL101 is still under study, particularly in early trials focusing on safety. Researchers are closely monitoring for side effects to ensure it remains safe for patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for adenoid cystic carcinoma?

Unlike the standard of care for adenoid cystic carcinoma, which often involves surgery, radiation, and chemotherapy, AL101 offers a new approach by targeting the Notch signaling pathway. This pathway plays a crucial role in the development and progression of several cancers, and AL101's ability to inhibit it could lead to more effective tumor control. Researchers are excited about AL101 because it is administered intravenously and has the potential to shrink tumors before surgery, making surgical removal easier and possibly improving surgical outcomes. This targeted mechanism differentiates AL101 from traditional treatments and holds promise for better patient outcomes.

What evidence suggests that AL101 might be an effective treatment for adenoid cystic carcinoma?

Research shows that AL101, which participants in this trial will receive, may help treat adenoid cystic carcinoma, especially when the NOTCH cell pathway is active. In earlier studies, AL101 controlled the disease in up to 71% of patients, with many experiencing tumor shrinkage or halted growth. AL101 blocks certain proteins that aid cancer cell growth, potentially making it effective against this cancer. Early results suggest it could slow or stop tumor growth before surgery. ^{1 4 5 6 7}

Who Is on the Research Team?

Renata Ferrarotto

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults with adenoid cystic carcinoma showing NOTCH1 pathway activation, who can consent to treatment and follow study rules. They must have a tumor that can be surgically removed and agree to use two forms of contraception if they're able to conceive. People with severe medical conditions, uncontrolled infections, or recent treatments for other cancers are excluded.

Inclusion Criteria

Total bilirubin > 1.5 upper limit of normal (ULN) (except known Gilbert's syndrome)

You are capable of giving informed consent.

My doctor believes my cancer can be surgically removed, either to try to cure it or to control its spread.

Exclusion Criteria

You have had an allergic reaction or are allergic to the ingredients in the investigational product.

I had cancer treatment at least 4 weeks ago for a local recurrence.

I have been treated with a gamma-secretase inhibitor before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AL101 intravenously over 60 minutes once weekly for 6-8 weeks

6-8 weeks

6-8 visits (in-person)

Surgery

Participants undergo surgery per standard of care within 24-72 hours after the last infusion of AL101

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks after surgery, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• AL101
• Therapeutic Conventional Surgery

Trial Overview The trial is testing AL101's effectiveness when given before surgery in patients with notch activated adenoid cystic cancer. It aims to see if AL101 can halt tumor growth by inhibiting certain enzymes needed for cell proliferation.

How Is the Trial Designed?

Group I: Treatment (AL101) Experimental Treatment 2 Interventions

Patients receive AL101 IV over 60 minutes QW for 6-8 weeks in the absence of disease progression or unacceptable toxicity. Within 24-72 hours after the last infusion of AL101, patients undergo surgery per standard of care. Patients may continue AL101 after surgery at the discretion of the study doctor.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11872804/

Clinical Outcomes With Notch Inhibitors in Notch‐Activated ... BOR revealed partial response in 17% of patients, stable disease in 55%, and progressive disease in 28%. Median response duration was longer for AL101 compared ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.6046

Results of ACCURACY: A phase 2 trial of AL101 ... Of the 77 evaluable subjects, there were 9 PRs (12%) and 44 SDs (57%) for a disease control rate of 69%. Conclusions: Investigational drug AL101 ...

3. nature.com nature.com/articles/s41419-022-05133-9

AL101, a gamma-secretase inhibitor, has potent antitumor ... AL101, a gamma-secretase inhibitor, has potent antitumor activity against adenoid cystic carcinoma with activated NOTCH signaling | Cell Death ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03691207

NCT03691207 | A Study Of AL101In Patients With Adenoid ... This is a Phase 2, non comparative, open label, multicenter study of AL101 in patients with recurrent or metastatic ACC who harbor NOTCH 1,2,3,4 activating ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02480-3/fulltext

900P Notch inhibitor AL101 prior to surgery in patients (pts) ... In a prior study of AL101 in metastatic NOTCH mutant ACC, the response rate (ORR) was 15% and disease control rate was 71% at the 4 mg dose. Here we conducted a ...

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)02885-5/fulltext

903P AL101 therapy in patients with recurrent/metastatic ... AL101 showed acceptable safety and tolerability in ACC pts with Notchmut and a response rate comparable to pooled estimates for available therapies in pts ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9355983/

AL101, a gamma-secretase inhibitor, has potent antitumor ... Specifically, we find that AL101 has potent antitumor effects in in vitro and in vivo models of ACC with activating NOTCH1 mutations and ...