A Study of AGEN2034 in Advanced Tumors and Cervical Cancer

NCT03104699 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: C-700-01
• Study Type: interventional
• Target: 211
• Locations: 8 countries
• Sites: 41

Brief 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.

Conditions

Advanced Cancer; Cervical Cancer

Keywords

Antibodies; Immunologic effects; Physiological Effects of Drugs

Outcome Measures

Primary Outcomes (3)

• Phase 1: Number of Participants Experiencing Dose-limiting Toxicities (DLTs) for Balstilimab

  A DLT was defined as any treatment-related toxicity that was National Cancer Institute Common Terminology Criteria for Adverse Event Grade ≥3, confirmed by the safety monitoring committee to be relevant for the study drug treatment, and that occurred during the first 3 weeks of balstilimab treatment in the dose escalation portion of the study (DLT evaluation period).

  21 days

• Phase 1: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)

  An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, which did not necessarily have a causal relationship with the treatment. TEAEs were AEs with onset dates during the on-treatment period, or the worsening of an event during the on-treatment period. A summary of all Serious Adverse Events and Other Adverse Events (nonserious), regardless of causality, is located in the 'Reported Adverse Events' Section.

  Up to 3 years

• Phase 2: Objective Response Rate (ORR) as Determined by an Independent Endpoint Review Committee (IERC)

  ORR was defined as percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR), as determined by an IERC per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). BOR was defined as the best response recorded from the start of the study treatment until the end of treatment. CR was defined as disappearance of all target lesions, and PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  Up to 3 years

Secondary Outcomes (15)

• Phase 1: Receptor Occupancy of Circulating T Cells

  4 hours after the first dose (Cycle 1 Day 1) and immediately prior to the second dose (Cycle 2 Day 1) (2-3 weeks/cycle)

• Phase 1: Maximum Observed Concentration (Cmax) of Balstilimab

  Day 1 (Pre-dose up to 24 hours post dose) of Cycle 1 and Cycle 2 (2-3 weeks/cycle) (up to 3 weeks)

• Phase 1: Area Under the Drug Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) of Balstilimab

  Day 1 (Pre-dose up to 24 hours post dose) of Cycle 1 and Cycle 2 (2-3 weeks/cycle) (up to 3 weeks)

• Phase 1: Number of Participants With Serum Anti-drug Antibodies (ADAs) for Balstilimab

  Up to 2.5 years

• Phase 2: Number of Participants Experiencing TEAEs

  Up to 3 years

Study Arms (1)

Monotherapy

EXPERIMENTAL

Dose of 3 mg/kg intravenous (IV) every 2 weeks for up to 24 months.

Drug: AGEN2034

Interventions

AGEN2034 DRUG

Anti-programmed cell death protein-1 (PD-1) Monoclonal Antibody

Also known as: Anti-PD-1

Monotherapy

Eligibility Criteria

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

You may qualify if:

• Voluntarily agree to participate by giving written informed consent. Participation in pharmacogenomics testing is optional.
• Be ≥18 years of age.
• Diagnosis and prior systemic treatment:
• Phase 1: Have a histologically or cytologically confirmed diagnosis of a metastatic or locally advanced solid tumor for which no standard therapy is available or standard therapy has failed.
• Phase 2: I. Have (1) a histologically or cytologically confirmed diagnosis of squamous-cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix, and (2) metastatic, locally advanced, and/or unresectable 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 advanced (recurrent, unresectable, or metastatic) disease; Note: Participants who have received \>1 prior systemic treatment regimen for their advanced or metastatic disease will be eligible in the following cases: Participant receiving chemotherapy concurrently with primary radiation (for example, weekly cisplatin) or participant receiving adjuvant chemotherapy following completion of radiation therapy (for example, paclitaxel and carboplatin for ≤4 cycles) and progressed within 6 months after treatment completion.
• Measurable disease - based on investigator assessment
• Phase 1: Have objective evidence of disease; the presence of measurable disease is not required.
• Phase 2: Have measurable disease on imaging based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Note: Participants must have at least one "target lesion" to be used to assess response, as defined by RECIST 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. Participants 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 performance status of 0 or 1.
• Have adequate organ function as indicated by the following laboratory values:
• Adequate hematological function defined by absolute neutrophil count ≥1.5 x 10\^9/liter (L), platelet count ≥100 x 10\^9/L, and stable hemoglobin ≥8 grams/deciliter (without transfusions within 1 week before first dose).
• Adequate hepatic function based by a total bilirubin level ≤ the institutional upper limit of normal (IULN), aspartate aminotransferase level ≤2.5 x IULN, alanine aminotransferase level ≤2.5 x IULN, and alkaline phosphatase ≤2.5 x IULN.
• Adequate renal function defined as creatinine ≤1.5 x IULN or calculated creatinine clearance ≥50 milliliters/minute for participants with creatinine levels \>1.5 x IULN (if no local guideline is available, creatinine clearance should be calculated using the Cockcroft-Gault Method).
• Adequate coagulation defined by international normalized ratio or prothrombin time ≤1.5 x IULN (unless the participant is receiving anticoagulant therapy); and activated partial thromboplastin time ≤1.5 x IULN (unless the participant is receiving anticoagulant therapy)
• Other than the cancer for which the participant is enrolled, have no history of prior malignancy, with the exception of basal cell carcinoma of the skin, superficial bladder cancer, squamous-cell carcinoma of the skin, or has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy.

You may not qualify if:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks before 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-programmed cell death ligand 1, or anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibodies
• For Phase 2: \>1 systemic treatment regimen for the advanced (recurrent, unresectable, or metastatic) cervical cancer for which the participant is considered for the study Note: In Phase 1, prior treatment with a CTLA-4 antibody is permissible for participants 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 Grade ≥3), any history of anaphylaxis, or uncontrolled asthma.
• Is receiving systemic corticosteroid ≤7 days prior to the first dose of trial treatment or receiving any other form of systemic immunosuppressive medication (corticosteroid use on study for management of immune-related adverse events, and/or a premedication for IV contrast allergies/reactions is allowed). Participants 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.
• Has a central nervous system tumor, metastasis(es), and/or carcinomatous meningitis identified either on the baseline brain imaging obtained during the screening period or identified prior to consent. Note: Participants with history of brain metastases that have been treated may participate provided they show evidence of stable supra-tentorial lesions at screening (based on 2 sets of brain images, performed ≥4 weeks apart, and obtained after the brain metastases treatment). In addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be minimal and be expected as sequelae from treated lesions. For individuals who received steroids as part of brain metastases treatment, steroids must be discontinued ≥7 days prior to first dose of study drug.
• Has active or history of autoimmune disease that has required systemic treatment within 2 years of the start of trial treatment (that is, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (that is, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Note: Participants with type 1 diabetes, vitiligo, psoriasis, hypo-, or hyperthyroid disease not requiring immunosuppressive treatment are eligible.

Sponsors & Collaborators

• Agenus Inc.: lead

Study Sites (44)

HonorHealth Research Institute

Scottsdale, Arizona, 85258, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

University of Southern California - Keck School of Medicine

Los Angeles, California, 90033, United States

Location

Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Florida Cancer Specialists & Research Institute

Sarasota, Florida, 34232, United States

Location

Augusta Oncology

Augusta, Georgia, 30912, United States

Location

Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Chicago, Illinois, 60611, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

The University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Swedish Medical Center-Cherry Hill Campus

Seattle, Washington, 98104, United States

Location

Pindara Private Hospital

Benowa, Queensland, 4217, Australia

Location

Calvary North Adelaide Hospital

North Adelaide, South Australia, 5006, Australia

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

IMIP

Recife, Pernambuco, 50070-550, Brazil

Location

Instituto Nacional de Câncer

Rio de Janeiro, Rio de Janeiro, 20220-410, Brazil

Location

Hospital de Caridade de Ijuí

Ijuí, Rio Grande do Sul, 98700-000, Brazil

Location

Hospital Mãe de Deus

Porto Alegre, Rio Grande do Sul, 90110-270, Brazil

Location

Instituto do Cancer do Estado de São Paulo

São Paulo, São Paulo, 01246-000, Brazil

Location

Hospital Amaral Carvalho

São Paulo, São Paulo, 03162-065, Brazil

Location

Fundação Faculdade Regional de Medicina de São José do Rio Preto

São José do Rio Preto, 15090-000, Brazil

Location

Centro Oncológico del Norte

Antofagasta, AN, 1240000, Chile

Location

Centro De Investigación Del Cancer James Lind

Temuco, AR, 4800827, Chile

Location

Fundación Arturo López Pérez

Santiago, RM, 7500918, Chile

Location

Bradford Hill

Santiago, RM, 8420323, Chile

Location

East-Tallinn Central Hospital

Tallinn, 1131, Estonia

Location

North Estonia Medical Centre Foundation

Tallinn, 13419, Estonia

Location

Institut Bergonié

Bordeaux, 33076, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

L'Institut Paoli - Calmettes

Marseille, 13273, France

Location

CHU Hôpital de la Timone

Marseille, 13385, France

Location

Centre Antoine-Lacassagne

Nice, 6189, France

Location

Hôpital Cochin

Paris, 75014, France

Location

Groupe Hospitalier Diaconesses Croix Saint-Simon - Hopital de la Croix Saint-Simon

Paris, 75020, France

Location

Clinique Armoricaine de Radiologie

Plérin, 22190, France

Location

Institute de Cancerologie de l'Ouest (ICO) - René Gauducheau

Saint-Herblain, 44805, France

Location

Institut Claudius Regaud

Toulouse, 31100, France

Location

Gustave Roussy

Villejuif, 94800, France

Location

Szpital Swietego Rafala w Krakowie

Krakow, Lesser Poland Voivodeship, 30-693, Poland

Location

Szpitale Pomorskie Sp. z o.o.

Gdynia, Pomeranian Voivodeship, 81-519, Poland

Location

Vall d'Hebron Institut d'Oncologia

Barcelona, 8035, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 8036, Spain

Location

Clínica Universidad de Navarra

Madrid, 28027, Spain

Location

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

balstilimab; spartalizumab

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

Results Point of Contact

• Title: Clinical Trial Information
• Organization: Agenus, Inc.

clinicaltrialinfo@Agenusbio.com

1-781-674-4265

Study Officials

• Medical Director

  Agenus Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

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: March 27, 2017
• First Posted: April 7, 2017
• Study Start: April 11, 2017
• Primary Completion: June 15, 2022
• Study Completion: June 15, 2022
• Last Updated: July 30, 2025
• Results First Posted: July 30, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2); AU (2); BR (7); BE (1); CL (4); US (12); FR (11); PL (2)