RECRUITING

AB821 in Adult Participants With Locally Advanced or Metastatic Solid Tumors

Conditions

Advanced Melanoma and Normal or Impaired Advanced Melanoma AB821 immune-responsive solid tumors

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This study is a first-in-human, open-label, nonrandomized, single center Phase 1 dose-escalation study to assess the safety, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary antitumor activity of AB821 monotherapy given every 2 weeks (Q2W) in participants with recurrent locally advanced or metastatic melanoma and other immune-responsive solid tumors. Immune-responsive solid tumors are defined as those for which immune checkpoint inhibitors form part of the standard-of-care therapy.

Official Title

An Open-Label, Phase 1 Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of AB821 in Adult Participants With Locally Advanced or Metastatic Melanoma and Other Solid Tumors

Quick Facts

Study Start:2025-08-05

Study Completion:2027-08

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT07027488

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:Yes

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. ≥18 years at the time consent is signed. 2. Ability to provide written informed consent for the study. 3. ECOG PS of 0 or 1. 4. Participants of childbearing potential must not be pregnant at enrollment and agree to comply with contraception requirements. Participants with partners of childbearing potential must also comply with contraception requirements. 5. Adequate organ function as defined below. Specimens must be collected within seven days prior to the start of the study treatment (i.e., Cycle 1 Day 1 \[C1D1\]) 6. Life expectancy of ≥12 weeks, per treating investigator's judgment. 7. For Melanoma participants: Participants with unresectable or metastatic melanoma that have progressed on or after PD 1/PD L1 checkpoint blockade (alone or with either CTLA 4 or LAG 3 checkpoint blockade). 8. For other tumor types: Must have a recurrent histologically or cytologically proven metastatic or locally advanced solid tumor, meeting each of the following: 1. Tumor that is not amenable to curative treatment with surgery or radiation. 2. Tumor for which immune checkpoint inhibitors form part of standard-of-care therapy. 3. Participant has received at least one prior line of systemic anticancer therapy in the recurrent or metastatic setting. 9. Has measurable disease per RECIST v1.1 as assessed by the local site investigator/radiology.	1. Has a diagnosis of immunodeficiency. 2. Prior stem cell, bone marrow, or organ transplant. 3. Known history of HIV infection. No HIV testing is required unless mandated by local health authority. 4. History of HBV (defined as HBV surface antigen reactive) or active HCV. 5. Active autoimmune disease (non-immunotherapy induced conditions) that has required systemic treatment in the past two years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic immune-suppressive treatment and is allowed. 6. Active Grade ≥2 diarrhea or enterocolitis. 7. Known active CNS metastases and/or carcinomatous meningitis. Individuals with previously treated brain metastases may participate provided they are radiologically stable (i.e., without evidence of progression for at least two weeks by repeat imaging, clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment). 8. Any other current or previous malignancy within the previous three years except neoplasms that, in the opinion of the treating investigator and with the agreement of the sponsor-investigator, will not interfere with study-specific endpoints, e.g. basal cell carcinoma, localized tumors that have been fully excised with curative intent and no evidence of recurrence or metastasis, prostate cancer that is asymptomatic and does not require therapy other than anti-androgen therapy. 9. Participant is a regular user, as determined by treating investigator judgment (including recreational use), of any illicit drugs or has a recent history (within the last year) of substance abuse (including alcohol), at the time of signing the Informed Consent Form (ICF). 10. Has clinically significant heart disease that affects normal activities, including, unstable angina, or history of congestive heart failure (New York Heart Association Class II IV). 11. History of acute myocardial infarction within the last six months. 12. Has a history of new or worsening thrombosis (DVT/PE, other thrombo-embolic disease) within the last six months. 13. Has a mean QTcF value of \>470 ms. 14. Has a history or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the individuals' participation for the full duration of the study, such that it is not in the best interest of the individual to participate, in the opinion of the treating investigator. 15. Has an active infection, requiring systemic therapy. 16. Has had a severe hypersensitivity reaction to any components of the study treatment or any of their excipients. 17. Is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within seven days prior the first dose of study treatment. 18. Has received more than five prior lines of systemic treatment in the recurrent/metastatic setting. 19. Has received prior radiotherapy within two weeks of start of study treatment or has had a history of radiation pneumonitis. 20. Has a history of grade 3-4 autoimmune myocarditis or a history of Guillain Barre Syndrome. 21. History of congestive heart failure with an ejection fraction \< 40%. 22. Participant with NSCLC only: Has received radiation therapy to the lung that is \>30 Gy within six months of the first dose of study treatment. 23. Has received previous IL-21 based therapy or prior therapy with AB248 24. Prior systemic anticancer therapy including investigational agents within 4 weeks (or, if shorter, within five half-lives for kinase inhibitors) prior to first dose of study treatment. 25. Major surgery from which the participant has not fully recovered 26. Has received a live or live attenuated vaccine within 30 days 27. Current use of any prohibited concomitant medications. 28. A participant of childbearing potential who has a positive serum pregnancy test within 14 days prior to treatment.

Inclusion Criteria

Exclusion Criteria

1. ≥18 years at the time consent is signed.
2. Ability to provide written informed consent for the study.
3. ECOG PS of 0 or 1.
4. Participants of childbearing potential must not be pregnant at enrollment and agree to comply with contraception requirements. Participants with partners of childbearing potential must also comply with contraception requirements.
5. Adequate organ function as defined below. Specimens must be collected within seven days prior to the start of the study treatment (i.e., Cycle 1 Day 1 \[C1D1\])
6. Life expectancy of ≥12 weeks, per treating investigator's judgment.
7. For Melanoma participants: Participants with unresectable or metastatic melanoma that have progressed on or after PD 1/PD L1 checkpoint blockade (alone or with either CTLA 4 or LAG 3 checkpoint blockade).
8. For other tumor types: Must have a recurrent histologically or cytologically proven metastatic or locally advanced solid tumor, meeting each of the following:
1. Tumor that is not amenable to curative treatment with surgery or radiation.
2. Tumor for which immune checkpoint inhibitors form part of standard-of-care therapy.
3. Participant has received at least one prior line of systemic anticancer therapy in the recurrent or metastatic setting.
9. Has measurable disease per RECIST v1.1 as assessed by the local site investigator/radiology.

1. Has a diagnosis of immunodeficiency.
2. Prior stem cell, bone marrow, or organ transplant.
3. Known history of HIV infection. No HIV testing is required unless mandated by local health authority.
4. History of HBV (defined as HBV surface antigen reactive) or active HCV.
5. Active autoimmune disease (non-immunotherapy induced conditions) that has required systemic treatment in the past two years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic immune-suppressive treatment and is allowed.
6. Active Grade ≥2 diarrhea or enterocolitis.
7. Known active CNS metastases and/or carcinomatous meningitis. Individuals with previously treated brain metastases may participate provided they are radiologically stable (i.e., without evidence of progression for at least two weeks by repeat imaging, clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment).
8. Any other current or previous malignancy within the previous three years except neoplasms that, in the opinion of the treating investigator and with the agreement of the sponsor-investigator, will not interfere with study-specific endpoints, e.g. basal cell carcinoma, localized tumors that have been fully excised with curative intent and no evidence of recurrence or metastasis, prostate cancer that is asymptomatic and does not require therapy other than anti-androgen therapy.
9. Participant is a regular user, as determined by treating investigator judgment (including recreational use), of any illicit drugs or has a recent history (within the last year) of substance abuse (including alcohol), at the time of signing the Informed Consent Form (ICF).
10. Has clinically significant heart disease that affects normal activities, including, unstable angina, or history of congestive heart failure (New York Heart Association Class II IV).
11. History of acute myocardial infarction within the last six months.
12. Has a history of new or worsening thrombosis (DVT/PE, other thrombo-embolic disease) within the last six months.
13. Has a mean QTcF value of \>470 ms.
14. Has a history or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the individuals' participation for the full duration of the study, such that it is not in the best interest of the individual to participate, in the opinion of the treating investigator.
15. Has an active infection, requiring systemic therapy.
16. Has had a severe hypersensitivity reaction to any components of the study treatment or any of their excipients.
17. Is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within seven days prior the first dose of study treatment.
18. Has received more than five prior lines of systemic treatment in the recurrent/metastatic setting.
19. Has received prior radiotherapy within two weeks of start of study treatment or has had a history of radiation pneumonitis.
20. Has a history of grade 3-4 autoimmune myocarditis or a history of Guillain Barre Syndrome.
21. History of congestive heart failure with an ejection fraction \< 40%.
22. Participant with NSCLC only: Has received radiation therapy to the lung that is \>30 Gy within six months of the first dose of study treatment.
23. Has received previous IL-21 based therapy or prior therapy with AB248
24. Prior systemic anticancer therapy including investigational agents within 4 weeks (or, if shorter, within five half-lives for kinase inhibitors) prior to first dose of study treatment.
25. Major surgery from which the participant has not fully recovered
26. Has received a live or live attenuated vaccine within 30 days
27. Current use of any prohibited concomitant medications.
28. A participant of childbearing potential who has a positive serum pregnancy test within 14 days prior to treatment.

Contacts and Locations

Study Contact

Stephanie Ladd

CONTACT

203-785-5702

stephanie.ladd@yale.edu

Principal Investigator

Harriet Kluger, MD

PRINCIPAL_INVESTIGATOR

Yale University

Study Locations (Sites)

Yale University

New Haven, Connecticut, 06510

United States

Collaborators and Investigators

Sponsor: Yale University

Harriet Kluger, MD, PRINCIPAL_INVESTIGATOR, Yale University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-08-05

Study Completion Date2027-08

Study Record Updates

Study Start Date2025-08-05

Study Completion Date2027-08

Terms related to this study

Keywords Provided by Researchers

AB821
immune-responsive solid tumors

Additional Relevant MeSH Terms

Advanced Melanoma and Normal or Impaired
Advanced Melanoma