AL102 for Desmoid Tumors

(RINGSIDE Trial)

Not currently recruiting at 64 trial locations

Overseen By Yelena Lalazar, RN, MPH

Age: Any Age

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Immunome, Inc.

Must not be taking: NSAIDs, Chemotherapy, TKIs, others

Disqualifiers: Recent malignancy, GI disease, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of a new treatment, AL102, for individuals with desmoid tumors. These tumors are non-cancerous but aggressive growths that can cause pain and other issues. The study will explore different doses of AL102 to determine the most effective one and includes a placebo (a non-active treatment) for comparison. It targets individuals diagnosed with desmoid tumors that have recently grown or cause pain not managed by regular medication. Participants must be able to swallow capsules and should not have recent cancer diagnoses or certain medical conditions, such as active infections or heart issues. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in desmoid tumor treatment.

Will I have to stop taking my current medications?

The trial requires that you stop any treatments for desmoid tumors, including chronic NSAIDs, at least 4 weeks before starting the study medication. However, the protocol does not specify if you need to stop other medications, so it's best to discuss this with the study team.

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

Research has shown that AL102 is safe and generally well-tolerated by patients in earlier studies. Its safety profile is similar to other drugs in its class, known as gamma secretase inhibitors (GSIs). Most participants tolerated the treatment well at all tested doses. Although GSIs have some common side effects, AL102's side effects are considered manageable. This means mild side effects might occur, but they are usually not serious and can be easily managed. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for desmoid tumors?

Researchers are excited about AL102 for desmoid tumors because it offers a novel approach by targeting the gamma-secretase enzyme, which is involved in the Notch signaling pathway. This pathway is crucial in the growth of desmoid tumors, and inhibiting it could help control tumor progression. Unlike traditional treatments like surgery, radiation, or non-specific systemic therapies, AL102 specifically interferes with the tumor's growth mechanism, potentially offering more targeted and effective management of the condition. Additionally, AL102 is being tested in different dosing regimens, including intermittent and daily schedules, allowing researchers to optimize its efficacy and safety profile for patients.

What evidence suggests that AL102 might be an effective treatment for desmoid tumors?

Research has shown that AL102 may help treat desmoid tumors. In this trial, participants will receive different dosages of AL102, including a 1.2 mg daily dose, which previous studies have shown to be effective. Patients who took this dose experienced early positive effects, and the treatment was manageable. In one study, patients stayed on the drug for over 10 months on average, and many did not see their condition worsen. This suggests that AL102 might slow tumor growth, offering hope for those with worsening desmoid tumors. ^{1 2 3 6 7}

Who Is on the Research Team?

Mrinal Gounder, MD

Principal Investigator

MSKCC

Are You a Good Fit for This Trial?

This trial is for adults with desmoid tumors that are growing and causing pain not controlled by non-opioid medication. Participants must have at least one tumor measurable by MRI, be able to swallow capsules, and can be treatment-naïve or have tried other treatments without success.

Inclusion Criteria

I agree to give a sample of my tumor for testing.

I can swallow pills and don't have stomach issues affecting drug absorption.

My tumor has been confirmed as a desmoid tumor by a pathologist.

Exclusion Criteria

Pregnant, breastfeeding, or expecting to conceive

I need assistance with daily activities due to my health condition.

Uncontrolled triglyceride elevations

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 2/Part A - Dose Regimen Finding

Open-label study to determine the optimal dose regimen of AL102 in patients with desmoid tumors

Approximately 6 months

Phase 3/Part B - Double Blind

Double blind, placebo-controlled study to evaluate the efficacy and safety of AL102

Approximately 18 months

Open Label Extension

Participants may opt into continuation of treatment with AL102 long-term

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AL102
• Placebo

Trial Overview The study tests the effectiveness and safety of a drug called AL102 compared to a placebo in patients with progressive desmoid tumors. The goal is to see if AL102 can help control the growth of these tumors better than no active treatment.

How Is the Trial Designed?

Group I: Part B AL102 Experimental Treatment 1 Intervention

AL102, recommended dose regimen from Part A, 1.2 mg daily

Group II: Part A Main Study 4 mg Intermittent Experimental Treatment 1 Intervention

AL102 4 mg

Group III: Part A Main Study 2 mg Intermittent Experimental Treatment 1 Intervention

AL102 2 mg

Group IV: Part A Main Study 1.2 mg daily Experimental Treatment 1 Intervention

AL102 1.2 mg

Group V: Open Label Extension Experimental Treatment 1 Intervention

AL102, recommended dose regimen from Part A, 1.2 mg daily

Group VI: Part B Placebo Placebo Group 1 Intervention

Placebo to match recommended dose regimen from Part A

Who Is Running the Clinical Trial?

Immunome, Inc.

Lead Sponsor

Trials

7

Recruited

420+

Ayala Pharmaceuticals, Inc,

Lead Sponsor

Trials

4

Recruited

340+

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.11515

RINGSIDE phase 2/3 trial of AL102 for treatment ... As of January 3, 2023, median time on study was 10.5 months (range 0.8 – 14.7) and 30 patients (71.4%) were still on study, 10 (23.8%) of whom ...

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)03376-3/fulltext

1766P Updated results of the RINGSIDE phase II trial and ... AL102 was well tolerated with a safety profile consistent with previously reported GSI toxicities. Efficacy of the 1.2 mg QD dose was demonstrated early and ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04871282?term=desmoid%20tumors&rank=5

A Study of AL102 in Patients With Progressing Desmoid ... Histologically confirmed desmoid tumor (aggressive fibromatosis) by local pathologist (prior to informed consent) that has progressed by ≥ 20% as measured by ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10873447/

Desmoid Tumors: Current Perspective and Treatment - PMC In phase 3, DeFi (Desmoid/Fibromatosis) trial, the risk of disease progression was 71% lower in the patients treated with nirogacestat than ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04871282

A Study of AL102 in Patients With Progressing Desmoid ... Study Overview. Brief Summary. The current study is designed to evaluate the efficacy and safety of AL102 in patients with progressive desmoid tumors.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11538224/

a systematic review and Bayesian network meta-analysis - PMC Desmoid tumors (DTs), also referred to as progressive fibromatosis, are rare, locally aggressive neoplasms originating from connective tissues.

7. immunome.com immunome.com/pipeline/al102-gamma-secretase-inhibitor/

Varegacestat (Gamma Secretase Inhibitor) The Phase 2 data also show that varegacestat was generally well tolerated with a manageable safety profile. Enrollment in RINGSIDE (Part B), a Phase 3 ...