Subjects With Metastatic or Locally Advanced Solid Tumors, and Expansion Into Select Solid Tumors (Cervical)
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|ClinicalTrials.gov Identifier: NCT03495882|
Recruitment Status : Recruiting
First Posted : April 12, 2018
Last Update Posted : July 22, 2019
|Condition or disease||Intervention/treatment||Phase|
|Cervical Cancer||Drug: AGEN1884 + AGEN2034||Phase 1 Phase 2|
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).
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)
- CDL−1 - 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 Management Committee (IDMC) will be established to evaluate safety and efficacy and an IERC will be established to adjudicate tumor response.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 / 2, Open-Label, Multi-Arm Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Biological, and Clinical Activity of AGEN1884 in Combination With AGEN2034 in Subjects With Metastatic or Locally Advanced Solid Tumors, and Expansion Into Select Solid Tumors|
|Actual Study Start Date :||December 18, 2017|
|Estimated Primary Completion Date :||March 4, 2022|
|Estimated Study Completion Date :||March 4, 2023|
Experimental: AGEN1884 + AGEN2034
AGEN1884 in combination with AGEN2034 in subjects with Subjects with Metastatic or Locally Advanced Solid Tumors, and Expansion into Select Solid Tumors (cervical)
Drug: AGEN1884 + AGEN2034
AGEN1884 + AGEN2034 according to protocol design
- Assess the safety and tolerability of AGEN1884 in combination with AGEN2034 [ Time Frame: From time of time of first dose until the end of follow-up (up to approximately 60 Weeks). ] ]Percentage of participants experiencing any unfavorable and unintended sign, symptom, disease, or worsening of pre-existing condition temporally associated with study therapy and irrespective of causality to study therapy.
- Overall Response Rate (ORR) per RECIST 1.1 [ Time Frame: Up to approximately 2 years ]ORR is the proportion of the participants who achieve complete response (CR) or partial response (PR) per RECIST 1.1 by Blinded independent central review (BICR)
- Duration Of Response (DOR) [ Time Frame: Up to approximately 2 years ]DOR is the time from first documented evidence of CR or PR per RECIST 1.1 by Blinded independent central review (BICR) until disease progression per RECIST 1.1 by BICR or death
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03495882
|Contact: Kristin Johnston, BSN, RNemail@example.com|
|Icon Cancer Care South Brisbane||Recruiting|
|South Brisbane, Australia|
|Contact: Mr Adam Stoneley +61 7 3737 4558 firstname.lastname@example.org|
|Principal Investigator: Jermaine Coward, MD|
|Scientia Clinical Research||Recruiting|
|Contact: James Kuo, MD +61 2 9382 5800 email@example.com|
|Principal Investigator:||Dr Jermaine Coward, MD||Icon Cancer Care South Brisbane|