Amivantamab in Adenoid Cystic Carcinoma

• ClinicalTrials.gov Identifier: NCT05074940
• Recruitment Status: Recruiting
• First Posted: October 12, 2021
• Last Update Posted: August 8, 2022
• Sponsor: Trisha Wise-Draper
• Information provided by (Responsible Party): Trisha Wise-Draper, University of Cincinnati

Study Description

Brief Summary:

The purpose of the study is to determine if treatment with amivantamab will be efficacious in patients with recurrent and metastatic adenoid cystic carcinoma.

Condition or disease	Intervention/treatment	Phase
Salivary Gland Cancer	Drug: Amivantamab	Phase 2

Detailed Description:

ACC is a rare cancer of salivary glands and other glandular tissue. It is slow growing and is usually treated with surgery and radiation. However, this type of cancer tends to have a high rate of recurrence and metastatic spread, which develops over several years. We hypothesize that amivantamab, a bispecific EGFR and MET inhibitor will be efficacious in ACC. Patients will receive amivantamab at 1050mg weekly for the first cycle and biweekly thereafter (1400mg for patients ≥80kg).

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Open-label phase II single arm trial
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study to Evaluate Amivantamab in Recurrent and Metastatic Adenoid Cystic Carcinoma
• Actual Study Start Date: August 5, 2022
• Estimated Primary Completion Date: August 5, 2023
• Estimated Study Completion Date: August 5, 2028

Arms and Interventions

Arm	Intervention/treatment
Experimental: Amivantamab; Amivantamab weekly for the first cycle and biweekly thereafter.	Drug: Amivantamab; Patients will receive amivantamab at 1050mg weekly for the first cycle and biweekly thereafter (1400mg for patients ≥80kg).

Outcome Measures

Primary Outcome Measures :

1. Overall response rate measured by RECIST criteria [ Time Frame: 2 years ]
   To determine the overall response rate in patients with recurrent and metastatic adenoid cystic carcinoma treated with amivantamab.

Secondary Outcome Measures :

1. Progression free survival -measured as time of treatment allocation to confirmed progressive disease or death. [ Time Frame: 5 years ]
   To determine the progression free survival and overall survival in patients with recurrent and metastatic adenoid cystic carcinoma treated with amivantamab.
2. Safety- measured by CTCAE v5 criteria and toxicity evaluation [ Time Frame: 5 years ]
   To determine safety of amivantamab in patients with recurrent and metastatic adenoid cystic carcinoma.

Other Outcome Measures:

1. Molecular signatures of response and resistance- measured by comprehensive analysis of Transcriptome Sequencing [ Time Frame: 2 years ]
   To determine the molecular signatures of response and resistance to amivantamab
2. Percent immune cell infiltration in responders versus non-responders, determined by IHC and/or IF [ Time Frame: 2 years ]
   To determine immune cell infiltration in biopsy samples and correlation with response.
3. Quality of life - measured via FACT-HN [ Time Frame: 2 years ]
   To evaluate the effect of amivantamab on patient quality of life using standardized patient reported outcome surveys.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Pathologically or cytologically confirmed adenoid cystic carcinoma. Non-salivary gland primary sites are allowed.
2. Recurrent and/or metastatic disease not amenable to other curative intent therapy.
3. Presence of measurable disease as defined by RECIST v1.1
4. Age ≥18 years.
5. ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).
6. Patients must have adequate organ and marrow function
7. Known human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
8. Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression in the last 4 weeks.
9. Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy.
10. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

Exclusion Criteria

1. History of allergy or intolerance to study drug components.
2. Prior use of amivantamab
3. Patients who have had chemotherapy or immunotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study. Palliative radiotherapy is allowed and does not require washout as long as it does not include a target lesion.
4. Positive hepatitis B (hepatitis B virus [HBV]) surface antigen (HBsAg) Note: Subjects with a prior history of HBV demonstrated by positive hepatitis B core antibody are eligible if they have at Screening 1) a negative HBsAg and 2) a HBV DNA (viral load) below the lower limit of quantification, per local testing. Subjects with a positive HBsAg due to recent vaccination are eligible if HBV DNA (viral load) is below the lower limit of quantification, per local testing.
5. Positive hepatitis C antibody (anti-HCV). Note: Subjects with a prior history of HCV, who have completed antiviral treatment and have subsequently documented HCV RNA below the lower limit of quantification per local testing are eligible.
6. Other clinically active or chronic liver disease.

7. Participant has active cardiovascular disease including, but not limited to:

   • A medical history of deep vein thrombosis or pulmonary embolism within 1 month prior to first dose of study drug or any of the following within 6 months prior to the first dose of study drug: myocardial infarction, unstable angina, stroke, transient ischemic attack, uncontrolled hypertension, or clinically significant cardiac arrythmia. Clinically non-significant thrombosis, such as non-obstructive catheter-associated clots, are not exclusionary.
   • Prolonged corrected QTcF >470 msec),
   • Congestive heart failure (CHF), defined as New York Heart Association (NYHA) class III-IV or hospitalization for CHF (any NYHA class; refer to Appendix: New York Heart Association Criteria) within 6 months of randomization.
8. Subject has uncontrolled inter-current illness, including but not limited to poorly controlled diabetes, ongoing or active infection (i.e., has discontinued all antibiotics for at least one week prior to first dose of study drug), or psychiatric illness/social situation that would limit compliance with study requirements. Subjects with medical conditions requiring chronic continuous oxygen therapy are excluded.
9. Active or past medical history of Interstitial lung disease (ILD)/pneumonitis, including drug-induced ILD/pneumonitis or radiation pneumonitis requiring treatment with prolonged steroids or other immune suppressive agents that is unresolved or resolved within the last 3 months.
10. Immune-mediated rash from checkpoint inhibitors that has not resolved prior to enrollment.
11. Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > Grade 1) with the exception of alopecia or Grade 2 neuropathy.
12. Patients who are receiving any other investigational agents. Patients who have received other investigational agents previously who are no longer receiving these investigational agents may be eligible at the discretion of the PI. A 30 day washout from last dose of previous anticancer drug is required.

Contacts and Locations

Contacts

Contact: UCCC Clinical Trials Office; 513-584-7698; cancer@uchealth.com

Contact: Christine Vollmer; 513-213-3203; mccordce@ucmail.uc.edu

Locations

United States, Ohio

University of Cincinnati Medical Center; Recruiting

Cincinnati, Ohio, United States, 45219

Contact: UCCC CTO 513-584-7698 cancer@uchealth.com

Principal Investigator: Trisha Wise-Draper, MD,PhD

Sponsors and Collaborators

Trisha Wise-Draper

Investigators

• Principal Investigator: Trisha Wise-Draper, MD, PhD; University of Cincinnati

More Information

• Responsible Party: Trisha Wise-Draper, Principal Investigator, University of Cincinnati
• ClinicalTrials.gov Identifier: NCT05074940
• Other Study ID Numbers: UCCC-HN-21-02
• First Posted: October 12, 2021
• Last Update Posted: August 8, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Trisha Wise-Draper, University of Cincinnati:

Salivary Gland Cancer; Amivantamab; Adenoid cystic carcinoma

Additional relevant MeSH terms:

Carcinoma; Salivary Gland Neoplasms; Carcinoma, Adenoid Cystic; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Mouth Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Mouth Diseases; Stomatognathic Diseases; Salivary Gland Diseases; Adenocarcinoma; Amivantamab-vmjw; Antineoplastic Agents, Immunological; Antineoplastic Agents