A Two-arm, Randomized, Non-comparative, Phase 2 Trial of AGEN2034 (Anti-PD-1) as a Monotherapy or Combination Therapy With AGEN1884 (Anti- CTLA4) or With Placebo in Women With Recurrent Cervical Cancer (Second Line) - RaPiDS
Overview
- Phase
- Phase 2
- Status
- Active, not recruiting
- Sponsor
- Agenus Inc.
- Enrollment
- 212
- Locations
- 68
- Primary Endpoint
- Objective Response Rate
Overview
Brief Summary
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.
Detailed Description
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 Patients will receive AGEN2034 with placebo as a monotherapy or with AGEN1884 as combination therapy for a maximum of 24 months or until confirmed progression, unacceptable toxicity, or any criterion for stopping the study drug or withdrawal from the trial occurs. Placebo administration in Treatment Arm 1 (AGEN 2034 monotherapy) of the study is intended to preserve the integrity of the investigators' interpretation of the efficacy and safety data by eliminating biases in disease assessment monitoring, declaration of disease progression, and assessment of toxicities. Therefore, it is understood that investigators, patients, and research personnel will not know whether patients have received AGEN2034/placebo (Treatment Arm 1) or AGEN2034/AGEN1884 (Treatment Arm 2).
An Independent Data Monitoring Committee (IDMC) will evaluate safety and efficacy. An IRRC will be established to adjudicate tumor response.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Voluntarily agree to participate by giving written informed consent. (Participation in pharmacogenomics testing is optional).
- •Be ≥18 years of age.
- •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.
- •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.
Exclusion Criteria
- •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.
Arms & Interventions
AGEN2034 + Placebo
AGEN2034 administered with placebo monotherapy: approximately 100 patients.
Intervention: AGEN2034 (Drug)
AGEN2034 + AGEN1884
AGEN2034 administered in combination with AGEN1884 (combination therapy): approximately 100 patients.
Intervention: AGEN2034 (Drug)
AGEN2034 + AGEN1884
AGEN2034 administered in combination with AGEN1884 (combination therapy): approximately 100 patients.
Intervention: AGEN1884 (Drug)
Outcomes
Primary Outcomes
Objective Response Rate
Time Frame: 48 months
To assess the Objective Response Rate (ORR) to the treatment of AGEN2034 (anti-PD-1) administered with placebo (Treatment Arm 1 - monotherapy), or with AGEN1884 (anti-CTLA4) (Treatment Arm 2 - combination therapy), defined as the binomial proportion of intent to treat (ITT) patients with best overall response (BOR) of complete response (CR) or partial response (PR), in women with recurrent/persistent/metastatic cervical cancer who have progressed following first-line therapy. BOR will be determined by the Independent Radiology Review Committee (IRRC), according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
Secondary Outcomes
- DOR per RECIST 1.1(48 months)
- Time to Confirmed Progression(48 months)
- Area under the concentration-time curve within time span t1 to t2 at steady-state (AUC(τ1-τ2)-ss)(48 months)
- Area under the drug concentration-time curve from time zero to time t (AUC(0-t))(48 months)
- Area under the drug concentration-time curve from time zero to infinity (AUC(0-∞))(48 months)
- Frequency, severity and duration of treatment-emergent AEs(48 months)
- Immunogenicity of AGEN2034(48 months)
- Maximum observed drug concentration at steady state (Cmax-ss)(48 months)
- Minimum observed drug concentration at steady-state (Cmin-ss)(48 months)
- Time to maximum drug concentration (tmax)(48 months)
- Terminal disposition rate constant (λz)(48 months)
- Terminal elimination half-life (t1/2)(48 months)
- Systemic clearance (CL)(48 months)
- Volume of distribution (Vd)(48 months)
- Quality of Life Assessment per FACT-Cx(35 months)
- Quality of Life Assessment per BPI(35 months)