Last updated on March 2020

Subjects With Metastatic or Locally Advanced Solid Tumors and Expansion Into Select Solid Tumors (Cervical)


Brief description of study

This is a Phase 1/2, open-label study of AGEN1884 in combination with AGEN2034 in subjects with locally advanced, recurrent and/or metastatic solid tumors including cervical cancer. AGEN2034 is a novel, fully human monoclonal immunoglobulin G4 (IgG4) antibody, designed to block program cell death-1 (PD-1). AGEN1884 is a novel, fully human monoclonal immunoglobulin G1 (IgG1) antibody, designed to block cytotoxic T-lymphocyte antigen-4 (CTLA-4).

Detailed Study Description

The trial consists of 2 phases:

  • Phase 1: Dose escalation
  • Phase 2: Expansion in advanced cervical cancer

Phase 1: Dose Escalation:

The enrollment to the Phase 1 portion of the study is completed. The trial will consist of a 3+3 dose escalation that will evaluate different combination dose levels (CDL) of AGEN1884 and AGEN2034 in subjects with locally advanced, recurrent and/or metastatic solid tumors.

Subjects may be enrolled to the following CDL cohorts:

  • CDL1 - AGEN1884 1 mg/kg every 6 weeks + AGEN2034 1 mg/kg every 2 weeks (starting CDL)
  • CDL2 - AGEN1884 1 mg/kg every 6 weeks + AGEN2034 3 mg/kg every 2 weeks (maximum planned CDL)
  • CDL1 - AGEN1884 0.3 mg/kg every 6 weeks + AGEN2034 1 mg/kg every 2 weeks (potential de-escalation CDL)

Combination Dose Level 1 (CDL1) will be the first to be tested. Dose escalation will continue until the maximum planned CDL (CDL2) is shown to be safe or the maximum tolerated dose (MTD) is reached. The MTD is defined as the CDL below which 33% of subjects develop dose-limiting toxicities (DLT). The decision to escalate to the next cohort will be made by a Safety Monitoring Committee (SMC), based on safety assessments after all subjects of a cohort reached the end of the DLT observation period of 21 days. Should 2 DLTs be observed in CDL1, the SMC may open enrollment to CDL-1. The SMC will also select the CDL for Phase 2.

Each subject will receive the combination treatment for a maximum of 24 months or until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the trial or the investigational medicinal products (IMPs) occur. Subjects who do not complete the DLT observation period of 21 days after the first dose, for reasons other than a DLT will be replaced. Additional subjects will be backfilled, concurrently with the 3+3 dose escalation schema at the lower cleared CDL, to ensure that each cohort enrolls at least 10 subjects. These additional subjects at each dose level will have the purpose of generating additional safety, PK, and receptor occupancy (RO) data, and will not undergo formal DLT observation.

The SMC selected CDL2 (AGEN1884 1 mg/kg every 6 weeks + AGEN2034 3 mg/kg every 2 weeks) as the Recommended Phase 2 dose (RP2D).

Phase 2: Expansion in Select Tumors

To further characterize safety and efficacy, the following expansion cohort will be enrolled:

Advanced cervical cancer In Phase 2, the RP2D of AGEN2034 and AGEN1884 will be administered for a maximum of 2 years or until confirmed progression, unacceptable toxicity, or any criterion for stopping the study drugs or withdrawal from the trial occurs.

For the Phase 2 portion of the trial, an Independent Data Monitoring Committee (IDMC) will be established to evaluate safety and efficacy and an IERC will be established to adjudicate tumor response.

Clinical Study Identifier: NCT03495882

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