A Study of AL102 in Patients With Progressing Desmoid Tumors

NCT04871282 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: AL-DES-01
• Study Type: interventional
• Target: 198
• Locations: 11 countries
• Sites: 53

Brief Summary

The current study is designed to evaluate the efficacy and safety of AL102 in patients with progressive desmoid tumors.

Conditions

Desmoid; Desmoid Tumor

Keywords

RINGSIDE

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Progression free survival (PFS) as defined as the time from randomization until the date of assessment of progression (as assessed by BICR based on RECIST v1.1) or death by any cause

  Approximately 2 years

Secondary Outcomes (6)

• Overall response rate

  Approximately 2 years

• Change in Tumor Volume

  Approximately 2 years

• Duration of response

  Approximately 2 years

• Progression Free Survival

  Approximately 2 years

• Patient reported outcome

  Approximately 2 years

Study Arms (6)

Part A Main Study 1.2 mg daily

EXPERIMENTAL

AL102 1.2 mg

Drug: AL102

Part A Main Study 2 mg Intermittent

EXPERIMENTAL

AL102 2 mg

Drug: AL102

Part A Main Study 4 mg Intermittent

EXPERIMENTAL

AL102 4 mg

Drug: AL102

Part B AL102

EXPERIMENTAL

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

Drug: AL102

Part B Placebo

PLACEBO COMPARATOR

Placebo to match recommended dose regimen from Part A

Other: Placebo

Open Label Extension

EXPERIMENTAL

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

Drug: AL102

Interventions

AL102 DRUG

AL102 is an inhibitor of gamma secretase-mediated Notch signaling.

Also known as: varegacestat

Open Label Extension; Part A Main Study 1.2 mg daily; Part A Main Study 2 mg Intermittent; Part A Main Study 4 mg Intermittent; Part B AL102

Placebo OTHER

Placebo to match AL102

Part B Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 18 years of age (inclusive) at the time of signing the informed consent form (ICF).
• Histologically confirmed desmoid tumor (aggressive fibromatosis) by local pathologist (prior to informed consent).
• Disease progression, assessed locally by the investigator, defined as having at least one of the following:
• Unidimensional growth of desmoid tumor(s) by ≥10%, using the sum of the largest diameters of target lesion(s), within 18 months of the screening MRI
• Having desmoid tumor-related pain that is not adequately controlled with nonopioid medication
• At least 1 measurable lesion amenable to volume measurements by MRI at screening (Part A only)
• One of the following:
• Treatment naïve subjects for whom, in the opinion of the investigator, the IP is deemed appropriate, OR
• Recurrent/refractory disease following at least one line of therapy (including surgery, radiation, or systemic therapy)
• Agrees to provide formalin-fixed paraffin embedded archival or fresh tumor tissue for re- confirmation of disease.
• Must be able to swallow whole capsules with no GI condition affecting absorption; nasogastric or G-tube administration is not allowed.

You may not qualify if:

• Diagnosed with a malignancy in the past 2 years with some exceptions.
• Current or recent (within 2 months of IP administration) GI disease or disorders that increase the risk of diarrhea, such as inflammatory bowel disease and Crohn's disease.
• Evidence of uncontrolled, active infection, requiring systemic anti-bacterial, anti-viral or anti- fungal therapy ≤7 days prior to administration of IP such as known active infection with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) at Screening.
• Myocardial infarction within 6 months prior to enrollment, greater than Class 1 angina pectoris, or has New York Heart Association (NYHA) Class III or IV heart failure, , symptomatic ventricular arrhythmias, sustained ventricular tachycardia, Torsade's de Pointes (TdP), the long QT syndrome, pacemaker dependence, or electrocardiographic evidence of acute ischemia.
• Unstable or severe uncontrolled medical condition (e.g., unstable cardiac or pulmonary function or uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the investigator's judgment, increase the risk to the subject associated with his or her participation in the study.
• Pregnant or breastfeeding or expecting to conceive children within the projected duration of the study.
• Eastern Cooperative Oncology Group (ECOG) performance status ≥2
• Abnormal organ and marrow function at Screening defined as:
• Neutrophils \<1000/mm3,
• Platelet count \<100,000/mm3,
• Hemoglobin \<9 g/dL,
• Total bilirubin \>1.5x upper limit of normal (ULN) (except known Gilbert's syndrome),
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \>2.5x ULN,
• Serum creatinine \> ULN and creatinine clearance (CrCl) \<60 mL/min (calculation of CrCl will be based on acceptable institution standard)
• Uncontrolled triglyceride ≥Grade 2 elevations per common terminology criteria for adverse events (CTCAE) v5.0 (\>300 mg/dL or \>3.42 mmol/L).

Sponsors & Collaborators

• Immunome, Inc.: lead

Study Sites (53)

Mayo Clinic

Pheonix, Arizona, 85054, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

Sarcoma Oncology Research Center

Santa Monica, California, 90403, United States

Location

University of California at Los Angeles Hematology/Oncology

Santa Monica, California, 90404, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

NorthShore University Health System

Evanston, Illinois, 60201, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02214, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Jefferson City Medical Group

Jefferson City, Missouri, 65109, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

University of Pittsburgh Medical Center, Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

UTSW Simmons Cancer Center

Dallas, Texas, 75235, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77005, United States

Location

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

Location

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Adelaide Cancer Centre

Kurralta Park, South Australia, 5037, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Universitair Ziekenhuis

Ghent, 9000, Belgium

Location

Universitaire Ziekenhuizen Leuven

Leuven, Belgium

Location

Helios Klinikum Berlin-Buch

Berlin, 13125, Germany

Location

Mannheim university medical center

Mannheim, 68167, Germany

Location

Oncology Institute Barzilai Medical Center

Ashkelon, Israel

Location

Rambam MC

Haifa, 3109601, Israel

Location

Hadassah University Hospital - Ein Kerem

Jerusalem, 9112001, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

IRCCS Istituto Ortopedico Rizzoli

Bologna, 40136, Italy

Location

IRCCS Fondazione Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Campus Bio-Medico University Hospital

Rome, 00128, Italy

Location

The Netherlands Cancer Institute

Amsterdam, 1066CX, Netherlands

Location

Leiden University Medical Center

Leiden, Netherlands

Location

Erasmus Medisch Centrum

Rotterdam, 3015 AA, Netherlands

Location

Maria Sklodowska-Curie National Research Institute of Oncology

Warsaw, 00-001, Poland

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

ASAN Medical Center

Seoul, 43-gil, South Korea

Location

Vall d´Hebrón University Hospital

Barcelona, 08035, Spain

Location

Catalan Institute of Oncology (ICO)

Barcelona, 08908, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Western General Hospital

Edinburgh, Scotland, EH4 2XU, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

The Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Desmoid Tumors

Condition Hierarchy (Ancestors)

Fibroma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Mrinal Gounder, MD

  MSKCC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2021
• First Posted: May 4, 2021
• Study Start: March 30, 2021
• Primary Completion: December 3, 2025
• Study Completion (Estimated): October 1, 2026
• Last Updated: February 5, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1); BE (2); DE (2); GB (4); AU (4); NL (3); US (23); IL (4); KR (2); IT (3); ES (5)