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

NCT03495882 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: C-550-01
• Study Type: interventional
• Target: 154
• Locations: 9 countries
• Sites: 47

Brief Summary

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).

Conditions

Cervical Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR), as determined by IERC, in the analysis population

  per RECIST 1.1

  Evaluated throughout the protocol, up to 2 years.

Secondary Outcomes (18)

• Safety and Tolerability of AGEN2034 and AGEN1884

  From the time of the first dose to the end of follow-up (up to 2 years after the last dose).

• Maximum drug concentration observed postdose at steady-state (Cmax-ss)

  Pre-dose through 3 months after last dose.

• Minimum observed concentration at steady-state (Cmin-ss)

  Pre-dose through 3 months after last dose.

• Area under the drug concentration-time curve within time span t1 to t2 at steady-state (AUC(τ1-τ2)-ss)

  Pre-dose through 3 months after last dose.

• Area under the drug concentration-time curve from time zero to time t (AUC(0-t)), area under the drug concentration-time curve from time zero to infinity (AUC(0-∞))

  Pre-dose through 3 months after last dose.

Study Arms (1)

AGEN1884 + AGEN2034

EXPERIMENTAL

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

Interventions

AGEN1884 + AGEN2034 DRUG

AGEN1884 + AGEN2034 according to protocol design

AGEN1884 + AGEN2034

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be eligible for participation in this trial the subject must:
• Voluntarily agree to participate by giving written informed consent. (Participation in pharmacogenomics testing is optional.)
• Be ≥18 years of age.
• Diagnosis:
• Phase 1: Male or female having a histologically or cytologically confirmed diagnosis of a locally advanced, recurrent, and/or metastatic solid tumor for which no standard therapy is available or standard therapy has failed.
• Phase 2:
• I. Female having (1) a histologically or cytologically confirmed diagnosis of squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix, and (2) locally advanced, recurrent, and/or metastatic disease at the time of enrollment. Histologic confirmation of the original primary tumor is required via pathology report.
• Note: The following cervical tumors are not eligible: minimal deviation/adenoma malignum, gastric type adenocarcinoma, clear cell carcinoma, and mesonephric carcinoma.
• II. Has cervical cancer and has relapsed after a platinum-based treatment (first line) regimen for locally advanced, recurrent, and/or metastatic disease; Note: Subjects who only received platinum-based chemotherapy concurrently with primary radiation (e.g., weekly cisplatin) or adjuvant chemotherapy following completion of radiation therapy (e.g., paclitaxel and carboplatin for ≤4 cycles) and progressed within 6 months after treatment completion will be eligible as this systemic therapy will be considered first line.
• Measurable Disease:
• Phase 1: Have objective evidence of disease; the presence of measurable disease is not required.
• Phase 2: Have measurable disease on imaging based on RECIST version 1.1. Note: Subjects must have at least one "target lesion" to be used to assess response, as defined by RECIST version 1.1. Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented, or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
• Note: Measurable disease by RECIST 1.1 must be confirmed by independent central radiologic review prior to first dose. Subjects without centrally confirmed measurable disease at baseline will not be eligible for this trial.
• Have a life expectancy of at least 3 months and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Have adequate organ function as indicated by the following laboratory values:

You may not qualify if:

• The subject must be excluded from participating in the trial if the subject:
• Is currently participating and receiving trial therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Has an inadequate washout period prior to first dose of study drug defined as:
• Received systemic cytotoxic chemotherapy or biological therapy within 3 weeks before first dose,
• Received radiation therapy within 3 weeks before first dose, or
• Had major surgery within 4 weeks before first dose.
• Has received prior therapy with:
• Any antibody/drug targeting T-cell co-regulatory proteins (immune checkpoints) such as anti-PD-1, anti-PD-L1, or anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibodies
• For Phase 2: \>1 systemic treatment regimen for the locally advanced recurrent, and/or metastatic cervical cancer for which the subject is considered for the study. Subjects who received a systemic regimen immediately after progressing within 6 months of completing chemotherapy concurrent with primary radiation or adjuvant chemotherapy after radiation will only be considered as having 1 prior systemic regimen for the purpose of this criterion.
• Note: In Phase 1, prior treatment with a CTLA-4 antibody is permissible for subjects with metastatic melanoma.
• Has persisting toxicity related to prior therapy of National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 (NCI-CTCAE) Grade \>1 severity.
• Note: Sensory neuropathy or alopecia of Grade ≤2 is acceptable.
• Is expected to require any other form of systemic or localized antineoplastic therapy while on trial (including maintenance therapy with another agent, radiation therapy, and/or surgical resection).
• Has known severe hypersensitivity reactions to fully human monoclonal antibodies (NCI-CTCAE Version 4.03 Grade ≥3), any history of anaphylaxis, or uncontrolled asthma.
• Is receiving systemic corticosteroid therapy ≤7 days prior to first dose of study treatment or receiving any other form of systemic immunosuppressive medication (corticosteroid use on study for management of immune-related adverse events (AE), and/or a premedication for intravenous (IV) contrast allergies/reactions is allowed). Subjects who are receiving daily corticosteroid replacement therapy are an exception to this rule. Examples of permitted therapy are daily prednisone at doses of 5 to 7.5 mg or equivalent hydrocortisone dose, and steroid therapy administered by topical, intraocular, intranasal, and/or inhalation routes.

Sponsors & Collaborators

• Agenus Inc.: lead

Study Sites (47)

Comprehensive Care and Research Center

Goodyear, Arizona, 85338, United States

Location

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

BRCR Medical Center, Inc

Plantation, Florida, 33322, United States

Location

Augusta University

Augusta, Georgia, 30912, United States

Location

Cancer Treatment Centers of America

Zion, Illinois, 60099, United States

Location

Ochsner Cancer Institute

New Orleans, Louisiana, 70121, United States

Location

West Michigan Cancer Center

Kalamazoo, Michigan, 49007, United States

Location

University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

Location

Chattanooga's Program In Women's Oncology

Chattanooga, Tennessee, 37403, United States

Location

CliniCore International

Baytown, Texas, 77521, United States

Location

Providence Regional Cancer System

Aberdeen, Washington, 98520, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

Linear Clinical Research

Perth, Western Australia, 6009, Australia

Location

Mater Research

South Brisbane, 4101, Australia

Location

Icon Cancer Care South Brisbane

South Brisbane, Australia

Location

Scientia Clinical Research

Sydney, Australia

Location

Clínica de Pesquisas e Centro de Estudos em Oncologia Ginecológica e Mamária Ltda.

São Paulo, 01317, Brazil

Location

IBCC - Instituto Brasileiro de Controle do Câncer

São Paulo, 03102, Brazil

Location

LLC Arensia Exploratory Medicine

Tbilisi, 0112, Georgia

Location

Magyar Honvedseg Egeszsegugyi Kozpont

Budapest, 1062, Hungary

Location

Orszagos Onkologiai Intezet

Budapest, 1122, Hungary

Location

Debreceni Egyetem

Debrecen, 4032, Hungary

Location

Bacs-Kiskun Megyei Korhaz

Kecskemét, 6000, Hungary

Location

Pecsi Tudomanyegyetem

Pécs, 7624, Hungary

Location

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont

Szeged, 6720, Hungary

Location

Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet

Szolnok, 5004, Hungary

Location

Zala Megyei Szent Rafael Korhaz

Zalaegerszeg, 8900, Hungary

Location

ARENSIA Exploratory Medicine Unit, Institute of Oncology

Chisinau, 2025, Moldova

Location

BioResearch Group SP. Z O.O.

Nadarzyn, 05-830, Poland

Location

Centrum Onkologii-Instytut im.M.Sklodowskiej Curie

Warsaw, 02-781, Poland

Location

ICO l'Hospitalet - Hospital Duran i Reynals

L'Hospitalet de Llobregat, 8908, Spain

Location

START Madrid. Oncology Phase I

Madrid, 28040, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Clinica Universidad de Navarra

Pamplona, 31008, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

CI Dnipropetrovsk CMCH #4 of Dnipropetrovsk RC Dept of Chemotherapy SI Dnipropetrovsk MA of MOHU

Dnipro, 49102, Ukraine

Location

CI Transcarpathian Cl Onc Center Dep of Surgery #1 SHEI Ivano-Frankivsk NMU

Ivano-Frankivsk, 76018, Ukraine

Location

Communal Non-profit Enterprise Regional Center of Oncology

Kharkiv, 61070, Ukraine

Location

CI of Healthcare Regional Clinical Specialized Dispensary of the Radiation Protection, Department of Surgery

Kharkiv, 61166, Ukraine

Location

Khmelnytskyi Regional Oncological Dispensary

Khmelnytskyi, 29000, Ukraine

Location

Medical Clinic Innovacia, LLC

Kiev, 07352, Ukraine

Location

Kyiv Сity Clinical Oncological Center

Kyiv, 03115, Ukraine

Location

Medical Center Oncolife

Kyiv, 04078, Ukraine

Location

Limited Liability Company Company Adonis

Kyiv, 08114, Ukraine

Location

Treatment-Prevention Institution Volyn Regional Oncological Dispensary

Lutsk, 43018, Ukraine

Location

Related Publications (1)

• O'Malley DM, Neffa M, Monk BJ, Melkadze T, Huang M, Kryzhanivska A, Bulat I, Meniawy TM, Bagameri A, Wang EW, Doger de Speville Uribe B, Hegg R, Ortuzar Feliu W, Ancukiewicz M, Lugowska I. Dual PD-1 and CTLA-4 Checkpoint Blockade Using Balstilimab and Zalifrelimab Combination as Second-Line Treatment for Advanced Cervical Cancer: An Open-Label Phase II Study. J Clin Oncol. 2022 Mar 1;40(7):762-771. doi: 10.1200/JCO.21.02067. Epub 2021 Dec 21.

  PMID: 34932394 DERIVED

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

balstilimab

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Medical Director

  Agenus Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2018
• First Posted: April 12, 2018
• Study Start: December 18, 2017
• Primary Completion: July 15, 2022
• Study Completion: July 15, 2022
• Last Updated: July 5, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

UA (10); GE (1); PL (2); BR (2); HU (8); ES (6); AU (4); US (13); MO (1)