NCT03104699

A Study of AGEN2034 in Advanced Tumors and Cervical Cancer

A Phase 1/2, Open-Label, Multiple Ascending Dose Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Biological, and Clinical Activity of AGEN2034 in Subjects With Metastatic or Locally Advanced Solid Tumors, With Expansion to Second Line Cervical Cancer

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 211 (actual)
• Sponsor: Agenus Inc. · Industry
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a 2-part trial: a Phase 1, open-label, dose-escalation study in participants with metastatic or locally advanced solid tumors, with a consecutive Phase 2 expansion to evaluate efficacy in participants with recurrent, unresectable, or metastatic (advanced) cervical cancer that has progressed after a platinum-based treatment regimen.

Detailed description

Phase 1: Dose Escalation Phase 1 will consist of a standard 3+3 dose escalation with the following escalating dose levels and schedules: Part A1: 1, 3, and 10 milligrams/kilogram (mg/kg) administered every 2 weeks Part A2: 6 and 10 mg/kg every 3 weeks Each participant will stay on the dose level and schedule assigned at trial entry. Participants will receive AGEN2034 for a maximum of 2 years or until confirmed progression, unacceptable toxicity, or any criterion for stopping the study drug or withdrawal from the trial occurs. A Safety Monitoring Committee (SMC) will assess safety; decide on dose-escalation and opening of backfill enrollment; define the recommended Phase 2 dose (RP2D); and determine opening of the Phase 2 cohorts. In Part A1, the first participant of each cohort will be observed for 16 days (that is, ≥48 hours after second dose) for occurrence of dose-limiting toxicity (DLT) before the second participant is administered trial medication. Thereafter, within each cohort, consecutively enrolled participants may initiate treatment ≥48 hours after the prior enrolled participant-initiated treatment. Dose escalation will continue until the maximum tolerated dose (MTD) is reached or the maximum planned dose level (10.0 mg/kg) is shown to be safe. The MTD is defined as the dose below which ≥2 DLTs are observed. Once Part A1 is completed, enrollment to Part A2 will begin. If \<2 DLTs are observed in Part A1 at the maximum planned dose of 10 mg/kg every 2 weeks, open enrollment to Part A2 will begin with enrollment of 10 participants at 6 mg/kg every 3 weeks, followed by open enrollment of 10 participants at 10 mg/kg every 3 weeks. If ≥2 DLTs are observed in Part A1, at the maximum planned dose in Part A1, the standard 3+3 dose escalation will resume with Part A2 where consecutively enrolled participants in dose escalation may initiate treatment ≥48 hours after the prior enrolled participant-initiated treatment. For cohorts in dose escalation, concurrent with the 3+3 dose escalation schema, additional participants will be backfilled to lower dose levels to ensure that each cohort enrolls a total of 10 participants. Participants enrolled to backfill cohorts may be enrolled simultaneously, without sequential dosing (that is, not required to wait 48 hours between 2 participants). These additional participants at each dose level will have the purpose of generating additional safety, pharmacokinetics, and receptor occupancy data, and will not undergo formal DLT observation. Phase 2: Dose Expansion To further characterize safety and efficacy, participants with recurrent, unresectable, or metastatic cervical cancer will be enrolled in Phase 2 and receive the RP2D of AGEN2034 (3 mg/kg every 2 weeks) for a maximum of 2 years or until confirmed progression, unacceptable toxicity, or any criterion for stopping the study drug or withdrawal from the trial occurs. An SMC will assess safety, and an Independent Data Monitoring Committee will evaluate safety and efficacy.

Conditions

• Advanced Cancer
• Cervical Cancer

Interventions

Type	Name	Description
DRUG	AGEN2034	Anti-programmed cell death protein-1 (PD-1) Monoclonal Antibody

Timeline

• Start date: 2017-04-11
• Primary completion: 2022-06-15
• Completion: 2022-06-15
• First posted: 2017-04-07
• Last updated: 2025-07-30
• Results posted: 2025-07-30

Locations

44 sites across 9 countries: United States, Australia, Belgium, Brazil, Chile, Estonia, France, Poland, Spain

Regulatory

• FDA-regulated drug study