AL101 Before Surgery for the Treatment of Notch Activated Adenoid Cystic Cancer

NCT04973683 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2021-0296NCI-2021-05878
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib trial studies the side effects and possible benefits of AL101 before surgery in treating patients with notch activated adenoid cystic cancer. AL101 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving AL101 before surgery may help to control adenoid cystic cancer that has a NOTCH pathway activation.

Conditions

Adenoid Cystic Carcinoma; Metastatic Adenoid Cystic Carcinoma

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  Adverse events will be graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Frequency tables will summarize toxicity data for all patients. Logistic regression may be utilized to assess the effect of patient prognostic factors on the response and toxicity.

  Up to 2 years

• Changes in NICD1 levels

  Evaluated by immunohistochemistry in the post-treatment surgical specimen (at 6 to 8 weeks) as compared to baseline (pre-treatment) in patients treated with AL101

  Baseline and after surgery

Secondary Outcomes (1)

• Overall response rate

  At 6-8 weeks

Study Arms (1)

Treatment (AL101)

EXPERIMENTAL

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.

Drug: AL101; Procedure: Therapeutic Conventional Surgery

Interventions

AL101 DRUG

Given IV

Also known as: AL 101, AL-101, BM-0018, BM0018, BMS-906024, GS/pan-Notch Inhibitor AL101

Treatment (AL101)

Therapeutic Conventional Surgery PROCEDURE

Undergo standard of care surgery

Treatment (AL101)

Eligibility Criteria

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

You may qualify if:

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent and in this protocol
• Age \>= 18 years old
• Histologically/cytological confirmed adenoid cystic carcinoma (ACC) of any primary site
• Evidence of NOTCH1 pathway activation as determined by NICD1 IHC nuclear staining in \>= 70% of tumor cells
• Patients must have surgically resectable disease, either with a curative intent or for local control in the setting of metastatic disease, in the opinion of the treating physician
• Patients must be willing to undergo baseline biopsy to obtain tumor material
• Disease must be measurable by RECIST 1.1
• Performance status Eastern Cooperative Oncology Group (ECOG) 0 or 1
• Neutrophils \< 1500/mm\^3
• Platelet count \< 100,000/mm\^3
• Hemoglobin \< 9 g/dL
• Total bilirubin \> 1.5 upper limit of normal (ULN) (except known Gilbert's syndrome)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \> 2.5 of upper limit of normality (ULN) OR \> 5 ULN for patients with liver metastases
• Creatinine clearance \< 40 mL/min (Calculation of creatinine clearance \[CrCl\] will be based on acceptable institution standard)
• Female patients with reproductive potential must practice two effective contraceptive measures for the duration of study drug therapy and for at least 90 days after completion of AL101 therapy. The two birth control methods can be either two barrier methods or a barrier method plus a hormonal method to prevent pregnancy. The following are considered adequate barrier methods of contraception: diaphragm, condom, copper intrauterine device, sponge, or spermicide. Appropriate hormonal contraceptives will include any registered and marketed contraceptive agent that contains an estrogen and/or a progestational agent (including oral, subcutaneous, intrauterine, or intramuscular agents)

You may not qualify if:

• Prior radiotherapy, chemotherapy, or biologic therapy is allowed in patients with loco-regional recurrent disease, if administered at least 4 weeks prior to study enrollment
• Prior treatment with gamma-secretase inhibitor
• History of previous malignancy other than malignancy treated with curative intent and with no evidence of active disease \>= 2 years before the first dose of study drug and of low potential risk for recurrence. Patients with the following diagnoses represents an exception and may enroll:
• Non-melanoma skin cancers with no current evidence of disease
• Melanoma in situ with no current evidence of disease
• Localized cancer of the prostate with prostate-specific antigen of \< 0.1 ng/mL
• Treated or localized well-differentiated thyroid cancer
• Treated cervical carcinoma in situ
• Treated ductal/lobular carcinoma in situ of the breast
• Evidence of clinically significant bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation)
• Evidence of uncontrolled, active infection, requiring systemic anti-bacterial, anti-viral or anti-fungal therapy =\< 7 days prior to administration of investigational product such as known active infection with hepatitis B and hepatitis C (HCV) at Screening
• Symptomatic central nervous system (CNS) metastases. Patients with asymptomatic CNS metastases as well as those with previously treated CNS metastases are eligible for enrollment in the study if at least four weeks has elapsed since last whole brain radiation treatment or at least two weeks has elapsed since last focal radiation treatment and the patient is deemed clinically stable by the investigator
• 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 patient associated with his or her participation in the study
• Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) \>= 480 msec
• Female subjects who are pregnant or breast-feeding

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Carcinoma, Adenoid Cystic

Interventions

BMS-906024

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Renata Ferrarotto

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2021
• First Posted: July 22, 2021
• Study Start: September 30, 2021
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: April 23, 2026

Record last verified: 2026-04

Locations

US (1)