NCT07027488

AB821 in Adult Participants With Locally Advanced or Metastatic Solid Tumors

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

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: Yale University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

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.

Detailed description

Phase 1 Dose-Escalation Participants with recurrent locally advanced or metastatic melanoma and immune-responsive solid tumors will be enrolled into dose-escalation cohorts. Patients with melanoma are required to have previously been treated with an inhibitor of PD1/L1, while patients with other solid tumors are required to have had previous systemic treatment regimen that may or may not include an inhibitor of PD1/L1. For DL3 and above, n ≥3; for DL1 and DL2, n=1, unless a Grade ≥2 AE or a DLT is observed, in which case the cohort will be expanded to at least 3 participants before further dose escalation. This will help determine the MTD or MAD and select the recommended Phase 1b or Phase 2 dose (RP1bD or RP2D). Participants in dose-escalation cohorts will be enrolled at least 48 hours apart and followed for dose-limiting toxicities for 28 days (completion of two 14-day cycles of treatment). Dose-Escalation Backfill Cohorts Based on emerging safety, PK, and pharmacodynamic data, additional participants may be enrolled in backfill cohorts, backfill slots may be used for other tumor types, not only melanoma, upon discussion with the sponsor-investigator at or below dose levels that cleared the dose-limiting toxicity (DLT) assessment and were determined to be safe and tolerable by the Data and Safety Monitoring Board (DSMB). Up to a maximum of 20 total participants may be enrolled in backfill cohorts, at the RP2D or at lower levels deemed efficacious to better assess safety and efficacy based on emerging data. Dose levels and justification are described in Section 4.3. This study consists of a Screening phase, a Treatment phase, an end of treatment (EOT) Visit, a 30-, 60-, 90- day Safety Follow-up (SFU) phase, and a long-term follow-up (LTFU) phase. Upon completion of the SFU phase post EOT, ongoing safety, disease progression, survival status, and subsequent anticancer therapies will be assessed in the LTFU period. During the treatment phase, participants who demonstrate disease progression per RECIST criteria may be allowed to continue AB821 if, in the opinion of the treating investigator, the participant is tolerating study treatment and deriving clinical benefit from continuing study treatment. If further progression is noted on subsequent imaging, participants may be allowed to continue on study based on discussion with the sponsor-investigator.

Conditions

• Advanced Melanoma and Normal or Impaired
• Advanced Melanoma

Interventions

Type	Name	Description
DRUG	AB821	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.

Timeline

• Start date: 2025-08-05
• Primary completion: 2027-08-01
• Completion: 2027-08-01
• First posted: 2025-06-18
• Last updated: 2026-02-25

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study