RaPiDS- A Phase 2 Study of Anti-PD-1 Independently or in Combination With Anti-CTLA-4 in Second-Line Cervical Cancer

Stopped early · Phase 2 · Has a placebo group

Conditions studied: Cervical Cancer

In brief

This is a randomized, blinded, non-comparative, two-arm Phase 2 clinical trial to assess the efficacy and safety of AGEN2034 administered with placebo (Treatment Arm 1 - monotherapy) or with AGEN1884 (Treatment Arm 2- combination therapy) for treatment of patients with advanced cervical cancer who relapsed or progressed after receiving first-line platinum-based chemotherapy. The study is not intended to compare the efficacy of the 2 experimental arms. Rather, the efficacy of each arm will be evaluated against its relevant historical controls as appropriate.

Key facts

Study ID

NCT03894215

Run by

Agenus Inc.

People needed

211

Starts

2019-06-01

Expected to finish

2025-03-26

Last updated by the study team

2026-03-27

Who can join

Age: 18 and older. Sex: female. Healthy volunteers: not accepted.

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:
• 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.
• Has cervical cancer and has relapsed after a platinum- based treatment (first line) regimen for advanced (recurrent, unresectable, or metastatic) disease.
• Measurable Disease:
• a. Have measurable disease on imaging based on RECIST version 1.1 by Investigator assessments and independent central radiologic review.
• Note: Patients without centrally confirmed measurable disease at baseline will not be eligible for this trial.
• Note: Patients must have at least 1 "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.
• 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:
• Adequate hematological function defined by absolute neutrophil count (ANC) > 1.5 x 10\^9/L, platelet count > 100 x 10\^9/L, and hemoglobin >8 g/dL (without transfusions within 1 week of first dose).
• Adequate hepatic function based by a total bilirubin level ≤ 1.5 the institutional upper limit of normal (IULN), aspartate aminotransferase (AST) level ≤ 2.5 x IULN, alanine aminotransferase (ALT) level ≤ 2.5 x IULN, and alkaline phosphatase ≤ 2.5 IULN and albumin ≥3.0 mg/dL.
• Adequate renal function defined as creatinine ≤ 1.5 × upper limit of normal (ULN) OR measured or calculated creatinine clearance ≥ 40 mL/minute per Institutional standard. Assessment methods should be recorded.
• Adequate coagulation defined by international normalized ratio (INR) or prothrombin time ≤ 1.5 x IULN (unless the patient is receiving anticoagulant therapy); and activated partial thromboplastin time (aPTT) ≤ 1.5 x IULN (unless the patient is receiving anticoagulant therapy)
• Has no history of another primary malignancy, with the exception of:
• Malignancy treated with curative intent and with no known active disease ≥ 3 years before the first dose of study drug and of low potential risk for recurrence.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease and superficial bladder cancer.
• Patients must provide a sufficient and adequate FFPE tumor tissue sample preferably from the most recent biopsy of a tumor lesion, collected either at the time of or after the diagnosis of advanced or metastatic disease has been made AND from a site not previously irradiated. Archival tumor tissue must be ≤ 3 years old. If no tumor tissue is available, a fresh biopsy will be required (See Section 7.2.3.1 for details).
• Note: Tissue from core biopsy or excisional biopsy or from resection is required.
• Patients must have a negative serum pregnancy test at screening (within 72 hours of first dose of study medication) if of childbearing potential or be of non-childbearing potential. Non-childbearing potential is defined as (by other than medical reasons):
• ≥45 years of age and has not had menses for greater than 1 year,
• Amenorrheic ≥ 2 years without a hysterectomy and oophorectomy and a follicle-stimulating hormone (FSH) value in the postmenopausal range upon pretrial (screening) evaluation,
• History of hysterectomy, oophorectomy or tubal ligation.

You may not qualify if…

• The patient must be excluded from participating in the trial if the patient:
• 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 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
• More than 1 systemic treatment regimen for the advanced (recurrent, unresectable, or metastatic) cervical cancer for which the patient is considered for the study.
• Has persisting toxicity related to prior therapy of National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (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.
• Has received systemic corticosteroid therapy ≤ 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 (AE), and/or a premedication for IV contrast allergies/reactions is allowed). Patients who are receiving daily corticosteroid replacement therapy are an exception to this rule. Daily prednisone at doses of up to 5 mg or equivalent hydrocortisone dose are examples of permitted replacement therapy.
• Has a central nervous system (CNS) 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: Patients 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 immunosuppressive systemic treatment within 2 years of the start of trial treatment (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (i.e., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of immunosuppressive systemic treatment.
• Note: Patients with diabetes type 1, vitiligo, psoriasis, hypo-, or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
• Has had an allogeneic tissue/solid organ transplant.
• Has or had interstitial lung disease (ILD) OR has had a history of pneumonitis that has required oral or IV corticosteroids.
• Has an active infection requiring intravenous (IV) systemic therapy.
• Has known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• Has known active Hepatitis B (HBV), Hepatitis C (HCV), or tuberculosis. Active Hepatitis B is defined as a known positive HBsAg result. Active Hepatitis C is defined by a known positive Hep C Ab result and known quantitative HCV ribonucleic acid (RNA) results greater than the lower limits of detection of the assay.
• Has clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 6 months of enrollment, unstable angina, congestive heart failure (New York Heart Association class ≥II), or serious uncontrolled cardiac arrhythmia requiring medication.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.

Where it is running

• University of South Alabama Mitchell Cancer Institute — Mobile, Alabama, United States
• Arizona Oncology - Biltmore Cancer Center — Phoenix, Arizona, United States
• Arizona Oncology - Tucson - Wilmot Road Location — Tucson, Arizona, United States
• University of California, San Diego (UCSD) - Moores Cancer Center — La Jolla, California, United States
• UCLA- Women's Health Clinical Research Unit (WHCRU) — Los Angeles, California, United States
• Gynecologic Oncology Associates — Newport, California, United States
• California Pacific Medical Center — San Francisco, California, United States
• University of California, San Francisco Medical Center — San Francisco, California, United States
• Baptist MD Anderson Cancer Center — Jacksonville, Florida, United States
• Moffitt Cancer Center — Tampa, Florida, United States
• Northside Hospital — Atlanta, Georgia, United States
• St Joseph's Hospital — Savannah, Georgia, United States
• Community Health Network - North Cancer Center — Indianapolis, Indiana, United States
• University of Kentucky Albert B. Chandler Hospital — Lexington, Kentucky, United States
• Ochsner Clinic Foundation — New Orleans, Louisiana, United States
• MD Anderson Cancer Center at Cooper — Camden, New Jersey, United States
• University of New Mexico Cancer Center — Albuquerque, New Mexico, United States
• Northwell Health Monter Cancer Center — Lake Success, New York, United States
• Laura and Isaac Perlmutter Cancer Center at NYU Langone — New York, New York, United States
• SUNY Upstate Medical University — Syracuse, New York, United States
• Albert Einstein College of Medicine — The Bronx, New York, United States
• Levine Cancer Institute — Charlotte, North Carolina, United States
• FirstHealth Outpatient Cancer Center — Pinehurst, North Carolina, United States
• MetroHealth Medical Center — Cleveland, Ohio, United States
• University of Alabama at Birmingham School of Medicine — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.