AB821 in Adult Participants With Locally Advanced or Metastatic Solid Tumors

NCT07027488 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 2000038990
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Melanoma and Normal or Impaired; Advanced Melanoma

Keywords

AB821; immune-responsive solid tumors

Outcome Measures

Primary Outcomes (7)

• Frequency of Dose-Limiting Toxicities (DLTs) in patients with advanced melanoma

  The primary objective of this outcome measure is to assess the number of participants experiencing dose-limiting toxicities (DLTs) during the study period. DLTs are specific adverse events (AEs) that are considered significant enough to prevent an increase in dose or continuation of treatment.

  From the date of enrolment to the final follow up visit, approximately two years after the first dose

• Frequency of Serious Adverse Events (SAEs) in patients with advanced melanoma

  This outcome measure aims to record the number of participants who experience serious adverse events (SAEs) while receiving AB821. An SAE is defined as any event that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.

  From the date of enrolment to the final follow up visit, approximately two years after the first dose

• Frequency of Treatment-Emergent Adverse Events (TEAEs) in patients with advanced melanoma

  This measure will track the number of participants experiencing treatment-emergent adverse events (TEAEs) during the study. TEAEs are adverse events that emerge following the start of treatment with AB821 and are not present prior to treatment or represent an exacerbation of a pre-existing condition.

  From the date of enrolment to the final follow up visit, approximately two years after the first dose

• Frequency of Adverse Events of Special Interest (AESIs) in patients with advanced melanoma

  This outcome measure focuses on the number of participants who experience adverse events of special interest (AESIs). AESIs are pre-specified medical occurrences that have been identified as important to monitor due to their potential impact on the risk-benefit profile of AB821.

  From the date of enrolment to the final follow up visit, approximately two years after the first dose

• Frequency of Adverse Events (AEs) Leading to Dose Interruption in patients with advanced melanoma

  The objective of this measure is to document the number of participants who experience adverse events that result in a temporary interruption of AB821 administration. The interruptions could be due to the severity of the adverse event making it necessary to halt the dosing temporarily.

  From the date of enrolment to the final follow up visit, approximately two years after the first dose

• Frequency of Adverse Events (AEs) Leading to Treatment Discontinuation in patients with advanced melanoma

  This outcome measure will track the number of participants who experience adverse events leading to the permanent discontinuation of treatment with AB821. These events warrant stopping the treatment altogether to ensure participant safety.

  From the date of enrolment to the final follow up visit, approximately two years after the first dose

• Frequency of Deaths in patients with advanced melanoma

  The primary objective of this measure is to record the number of participants who die during the study period, irrespective of the cause. This encompasses any deaths occurring within the timeframe of the study and helps to monitor the overall impact of the study treatment on participant mortality.

  From the date of enrolment to the final follow up visit, approximately two years after the first dose

Secondary Outcomes (11)

• Maximum Concentration (Cmax) of AB821 in Serum

  From the date of enrolment to the final follow up visit, approximately two years after the first dose

• Assessing the immunogenicity of AB821 in patients with advanced melanoma

  From the date of enrolment to the final follow up visit, approximately two years after the first dose

• Objective Response Rate (ORR) of AB821 in Patients with Advanced Melanoma

  Screening, day 1 of cycle 4 (each cycle is 14 days), end of treatment and at long term follow up

• Duration of Response (DOR) of AB821 in Patients with Advanced Melanoma

  Screening, day 1 of cycle 4 (each cycle is 14 days), end of treatment and at long term follow up

• Disease Control Rate (DCR) of AB821 in Patients with Advanced Melanoma

  Screening, day 1 of cycle 4 (each cycle is 14 days), end of treatment and at long term follow up

Study Arms (1)

AB821

EXPERIMENTAL

AB821 is intended to be administered as a 30-minute IV infusion every 2 weeks. Dosage is calculated per body weight.

Drug: AB821

Interventions

AB821 DRUG

AB821 will be administered via IV infusion using weight-based dosing. AB821 will be administered over 30 minutes +/- 10 minutes. Participants will receive AB821 on Day 1 of each 14 day cycle for up to two years.

AB821

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 years at the time consent is signed.
• Ability to provide written informed consent for the study.
• ECOG PS of 0 or 1.
• 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.
• 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 \[C1D1\]) including:
• ANC\> 1500/ul Platelet count\>100,000 Hb\>9 g/dl Calculated creatinine clearance\> 50 mL/min Total bilirubin greater than or equal to 1.5 x ULN or direct bilirubin greater than or equal to ULN for participants with total bilirubin \> 1.5 x ULN PT INR \> 1.5 x ULN unless on anticoagulation Albumin \> 3g/dl
• Life expectancy of ≥12 weeks, per treating investigator's judgment.
• 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).
• For other tumor types: Must have a recurrent histologically or cytologically proven metastatic or locally advanced solid tumor (non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), Merkel-cell carcinoma, bladder cancer, or squamous cell carcinoma of the head and neck (SCCHN)), meeting each of the following:
• Tumor that is not amenable to curative treatment with surgery or radiation.
• Tumor for which immune checkpoint inhibitors form part of standard-of-care therapy.
• Participant has received at least one prior line of systemic anticancer therapy in the recurrent or metastatic setting.
• Has measurable disease per RECIST v1.1 as assessed by the local site investigator/radiology.

You may not qualify if:

• Has a diagnosis of immunodeficiency.
• Prior stem cell, bone marrow, or organ transplant.
• Known history of HIV infection. No HIV testing is required unless mandated by local health authority.
• History of HBV (defined as HBV surface antigen reactive) or active HCV.
• 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.
• Active Grade ≥2 diarrhea or enterocolitis.
• 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).
• 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.
• 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).
• 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).
• History of acute myocardial infarction within the last six months.
• Has a history of new or worsening thrombosis (DVT/PE, other thrombo-embolic disease) within the last six months.
• Has a mean QTcF value of \>470 ms.
• 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.
• Has an active infection, requiring systemic therapy.

Sponsors & Collaborators

• Yale University: lead
• Asher Biotherapeutics, Inc.: collaborator

Study Sites (1)

Yale University

New Haven, Connecticut, 06510, United States

RECRUITING

Study Officials

• Harriet Kluger, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stephanie Ladd

CONTACT

203-785-5702; stephanie.ladd@yale.edu

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: May 19, 2025
• First Posted: June 18, 2025
• Study Start: August 5, 2025
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: February 25, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)